Chemotherapy scheme ep. Chemotherapy - types, schemes, side effects, cost

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Malignant tumors of the ovaries

World Health Organization (WHO) and International Association of Obstetricians and Gynecologists (FIGO) a unified morphological classification of malignant ovarian tumors was adopted, which distinguishes epithelial tumors, sex cord stromal tumors and germ cell tumors.

Most malignant tumors (80-90%) are epithelial.

Among them, serous cystadenocarcinoma - 42%, mucinous cystadenocarcinoma - 12%, endometrioid carcinoma - 15%, undifferentiated carcinoma - 17%, clear cell carcinoma - 6%.

Borderline (potentially low malignancy) tumors were identified in the main types. They make up about 15% of epithelial tumors. In addition to the morphological type of tumor, the most important independent prognostic factor in the effectiveness of treatment and survival of patients is the degree of cellular differentiation of epithelial tumors, which determines the degree of its malignancy. The Broders histological assessment system is used, and the I degree of differentiation is more favorable prognostically and the III degree is the least favorable (G1 - highly differentiated, G2 - medium, G3 - low-differentiated).

Of all tumors of stromal origin, including granulosa-, thecacollagen-producing, as well as Sertoli / Leydigo-stromal cells or their embryonic precursors, the granulosa cell tumor is the most common.

Germ cell tumors account for less than 5% of all malignant ovarian tumors, but are important because they occur in young girls and women and require special treatment, different from other ovarian tumors. The most common among these tumors are dysgerminoma, similar to testicular seminoma (tumor of endodermal origin), and embryonic cancer, in which there is an increase in the level of tumor markers (serum and a-fetoprotein).

Borderline tumors, or tumors with low malignancy potential, account for approximately 15% of all epithelial ovarian tumors.

Obligatory morphological confirmation of the diagnosis of such a tumor is necessary, since its prognosis and treatment are completely different from other malignant neoplasms.
A review of 22 studies (953 patients) with a mean follow-up of 7 years showed a survival rate of 92% for advanced disease with the exception of invasive tumor implants.

The method of treatment of borderline tumors is an operation, the volume of which is determined by the stage of the process, the age of the patient and her desire to preserve reproductive function. Patients with a common process perform radical operations in the amount of extirpation or supravaginal amputation of the uterus with appendages, removal of the greater omentum and all tumor nodes in the form of the so-called aggressive cytoreduction.

Patients with residual borderline tumors do not undergo chemo- and radiation therapy, since numerous studies (including those at the N.N. Blokhin Russian Cancer Research Center of the Russian Academy of Medical Sciences) do not show its significance. Patients without residual tumors who do not receive adjuvant treatment have the same or better survival results when compared with the treatment group.

In cases of rapid growth of residual tumors and their repeated removal, some authors use melphalan or cisplatin.

ovarian cancer

Ovarian cancer is one of the most common malignant gynecological tumors and ranks 5th in cancer mortality among women. 50% of all cases occur in people over 65 years of age. The 5-year survival rate improves significantly over time, from 36% in the mid-1970s to 45% in 2002. Approximately 5-10% of ovarian cancer is familial in the three most common variants: ovarian cancer alone, ovarian cancer, and cancer breast, ovarian and colon cancer.

First of all, heredity is traced in relatives of the first degree (mother, daughter, sister). Less at risk for women of the second degree of kinship (grandmother, aunt). Genetic studies reveal BRCA1 mutations at the 17q21 locus. The BRCA2 gene, also responsible for familial ovarian cancer and breast cancer (BC), located on chromosome 13q12.

Prophylactic oophorectomy may be considered in women at increased risk over 35 years of age with children, but its relevance has not yet been fully established. Cases of the disease after prophylactic surgery are described, starting with peritoneal tumor growths similar to ovarian cancer.

A feature of ovarian cancer is spread into the abdominal cavity by cell implantation and local invasion into the bladder and intestines. The incidence of lymph node involvement is 24% in stage I, 50% in stage II, 74% in stage III, and 73% in stage IV. The pelvic lymph nodes are involved as often as the para-aortic ones. The tumor, by transdiaphragmatic spread, can block diaphragmatic lymphatic drainage, which causes ascites and pleurisy.

The most informative prognostic factors for ovarian cancer include the following (Table 9.23).

Table 9.23. Main prognostic factors in ovarian cancer

Note. "+" - favorable; "-" - unfavorable, "±" - intermediate

For patients with stage I, the degree of morphological differentiation of the tumor is most important. Flow cytometric analysis of DNA in stages I and IIA can identify an increased risk group.

After optimal operations in stage III, the median survival is 52-63 months.

In table. Figure 9.24 shows the FIGO classification of ovarian cancer.

Table 9.24. Classification of ovarian cancer (FIGO)

The survival of patients directly depends on the stage of the process (Table 9.25).

Table 9.25. Survival of patients according to FIGO stages

To diagnose and monitor the effectiveness of treatment in epithelial tumors, tumor markers such as cancer embryonic antigenREA) and tumor-specific antigen CA-125. There is a high correlation of the level of CA-125 one month after the 3rd course chemotherapy (XT) at III and IV stages and survival. In cases of normalization of this marker during treatment, its repeated increase determines the activation of the process, although it does not mean the need for immediate treatment.

An elevated CA-125 level indicates a high probability of ovarian cancer, while a negative response does not rule out the presence of a residual tumor. The level of CA-125 can be elevated both in other malignant tumors and in various diseases of the genital organs, such as endometriosis.

Treatment methods depend on the stage of the process. Surgery is the key to treatment. Unlike other tumors of the female genital organs, the stage of the process with ovarian cancer is established after surgery. Despite the fact that only a small number of patients can be cured by a single operation, the success of therapy is determined by the amount of initial intervention. The possibility of achieving subsequent complete remission, confirmed morphologically, depends on the size of the residual tumors.

Bilateral ovariosalpingectomy with hysterectomy and removal of the greater omentum is considered a radical operation for ovarian cancer. In young women who insist on preserving reproductive function, with stage I and grade I (G1), unilateral oophorectomy is possible.

During the operation, to clarify the stage and morphological variant, a biopsy is taken from the lateral canals, the pelvic peritoneum and diaphragm, the ligament that suspends the ovary, para-aortic, common iliac, external and internal iliac lymph nodes, serosa of the rectum and bladder.

Studies have not shown improvement in long-term outcomes with neoadjuvant XT. Currently, aggressive operative tactics as initial therapy are considered to be preferred for best survival. However, in case of doubtful success of the operation in patients with potential complications and comorbidities, neoadjuvant XT is possible.

Treatment tactics

Stage I

Patients with tumors in stage IA-IB with a high or medium degree of differentiation (i.e. I-II degree of malignancy, G1-G2) do not require additional treatment after surgery.

At III degree of malignancy (G3) stage 1C, the probability of recurrence is high (up to 20%), which requires additional methods of treatment.

Systemic chemotherapy, intraperitoneal (ip) administration of radioactive phosphorus 32P, or irradiation of the abdominal cavity and small pelvis are possible. However, the administration of 32P turned out to be more toxic with the same efficiency when compared with 6 courses of cisplatin.

Stage II

After surgical treatment, adjuvant XT is performed according to the TC scheme.

Stage III

Extirpation or supravaginal amputation of the uterus with appendages with resection of the greater omentum and removal of all or most of the tumors. In the absence of visible tumors, multiple biopsies and washings from the abdominal cavity are performed.

Further treatment includes the following:

1. With minimal residual tumors (
Perhaps total irradiation of the abdominal cavity and small pelvis (only if there are no macroscopic manifestations of the disease in the abdominal cavity and there are minimal residual tumors less than 0.5 cm in diameter in the pelvic cavity) or intravenous administration of 32R (only if residual tumors less than 1 cm) or colloidal radioactive gold.

2. In case of macroscopic residual tumors more than 2 cm in diameter in the pelvic cavity, combined chemotherapy is performed in the TC, TP, CP or CC mode.

The effectiveness of XT is assessed clinically, radiologically and by marker level. Increasingly important for confirmation of complete remission is positron emission tomography (PAT).

Research programs have demonstrated a statistically significant improvement in relapse-free survival in patients with minimal residual tumors treated with ip cisplatin and ip and iv paclitaxel compared to those who received only iv cisplatin with paclitaxel. These data open up prospects for intraperitoneal chemotherapy in patients with minimal residual tumors.

Stages III and IV. Operations in full and cytoreductive to remove the largest volume of tumor masses, after which a combined XT is performed.

Therapeutic approaches for stage III and IV ovarian cancer are the same, despite the fact that the prognosis for patients with stage IV is worse. In patients with stage IV, the main manifestation is usually large tumors in the abdominal cavity and cytoreductive surgery, if possible, should be carried out in order to minimize the volume of tumor masses as much as possible.

The volume of residual tumors is a prognostic factor that significantly affects survival. Median survival in patients after optimal cytoreductive surgery is 39 months, and after suboptimal cytoreduction - only 17 months. In case of technical impossibility of performing the operation, treatment can be started with chemotherapy in order to re-evaluate the possibility of cytoreductive surgery after 3 courses. The value of repeated cytoreductive operations has not been proven.

Chemotherapy

Platinum derivatives form the basis of first-line XT combinations for advanced ovarian cancer. The standard dose is cisplatin 75 mg/m2 and carboplatin AUC-6.0~7.5.

Cisplatin and carboplatin are equivalent in efficacy in ovarian cancer. Few studies have shown superiority of carboplatin (AUC 7.5) + paclitaxel (175 mg/m2) 3-hour infusion over cisplatin (75 mg/m2) + paclitaxel (135 mg/m2) 24-hour infusion.

An alternative to the paclitaxel regimen is the docetaxel and carboplatin regimen, which has shown similar efficacy in a comparative study with greater hematologic and lower neurotoxicity. Survival at 2 years of follow-up remains the same. The TC regimen (paclitaxel and carboplatin) is considered to be the best for initial XT in terms of efficacy, toxicity, and patient quality of life. Cisplatin is associated with greater neuro-, nephro-, oto-, and gastrointestinal toxicity but less myelosuppression than carboplatin.

Despite anecdotal evidence of equivalent efficacy for HT, ATS, and carboplatin monotherapy (ICON-3) regimens, most authors consider HT to be the preferred regimen.

Docetaxel may replace paclitaxel in cases where neurotoxicity needs to be reduced. Adding a third agent to such combinations is not justified.

Starting regimen: paclitaxel 175 mg/m2 3-hour infusion and carboplatin AUC 6.0-7.5 (high dose for patients in good general condition) every 3 weeks for a total of 6 cycles. Chemotherapy should be started after 4-6 weeks. after operation.

Intraperitoneal XT in a comparative study showed a significant improvement in median progression-free survival (29.8 vs 18.3 months) and overall survival (65.6 vs 49.7 months).

This type of treatment may be considered for patients with minimal residual tumors, as It is for this category of patients that it has an advantage: the median survival for minimal tumors is 66 months, and for large residual tumors - 26 months.

The preferred regimen studied is as follows: paclitaxel 135 mg/m2 IV 24-hour infusion on day 1. Sequentially cisplatin 100 mg/m2 i.p. on day 2 and paclitaxel 60 mg/m2 i.p. on day 8. There are six 21-day courses of treatment in total.

This approach should be discussed in detail with the patient as is associated with more significant toxicity than intravenous XT. In addition to catheter-related complications (infection, prolapse, blockage), it may be accompanied by grade III-IV fatigue, neutro- and thrombocytopenia, as well as gastrointestinal toxicity, abdominal pain, metabolic disorders, and neuropathy. Intraperitoneal therapy should be carried out only in clinics with relevant experience.

New drugs such as gemcitabine (Gemzar), oxaliplatin, topotecan, and triple regimens including epirubicin (Pharmorubicin) and altretamine continue to be studied with promising results.

Maintenance and consolidation chemotherapy, as well as high-dose XT, is not justified due to the lack of data on improving overall survival.

Relapses of ovarian cancer. Second line chemotherapy

The most important predictors of ovarian cancer recurrence are clinical stage and size of residual tumors (Table 9.26).

Table 9.26. Predictive factors for ovarian cancer recurrence

The age of patients also matters: 5-year survival in women younger and older than 40 years correlates as 65 and 20%. Other negative factors include clear cell or mucinous histology, low differentiation, poor general condition, non-platinum first line XT regimens, presence of ascites. The overall recurrence rate is 62%.

The choice of second-line chemotherapy is based on tumor sensitivity to first-line XT.

Allocate:

Platinum-sensitive tumors - the first line with platinum derivatives is effective, the relapse-free interval is more than 6 months;
platinum-resistant - relapse-free interval is less than 6 months;
refractory cases - patients progress in the process of the first line XT.

Recurrent ovarian cancer may be clinically manifested by new symptoms or radiographic findings. computed tomography (CT), as well as an increase in the level of CA-125, which may precede other symptoms for 6 months. and more.

For women with asymptomatic relapses, the appropriateness of immediate treatment should be carefully considered and discussed.

The goal is palliative treatment with long-term remissions, since a cure in this situation is unlikely. Immediate initiation of treatment is justified for patients with symptoms of the disease, as well as in the presence of a small tumor volume that responds better to chemotherapy. The greatest efficacy is likely in patients with a platinum-sensitive relapse and a relapse-free interval of 12-24 months. and more. It is up to 60% with a median survival of up to 2-4 years. These patients are subject to immediate treatment.

For patients with platinum-resistant recurrence and a short relapse-free period, treatment can be delayed until a certain point (appearance of symptoms, etc.), and only the growth of the CA-125 marker requires further monitoring.

For platinum-sensitive relapses, resumption of platinum-containing regimens, primarily TC or TR, is the treatment of choice. The exception is clear cell adenocarcinoma (mesonephroid), which is relatively resistant to these regimens.

Other regimens may be: liposomal doxorubicin + carboplatin or carboplatin + gemcitabine. The latter regimen is preferred for patients with residual neurotoxicity after first line XT.

Combined XT showed better results compared to monotherapy with one of the platinum derivatives. Success depends on the duration of the relapse-free interval: if it is 5-12 months. - effect 27%, s pathomorphological complete remission (pPR)- 5%, 13-24 months. - 33% and PPR - 11%, more than 24 months. - 51% and PPR - 22%.

Platinum-resistant relapses

Paclitaxel should be used if it has not been used in first-line chemotherapy.

The drug of choice for platinum- and taxane-resistant relapses is liposomal doxorubicin (Doxil in the US, Kelix in Europe). Oral etoposide, topotecan, gemcitabine, vinorelbine, 5-fluorouracil (5-FU) with leucovorin and ifosfamide have some efficacy. Altretamine (Hexalen) and oxaliplatin may also be used.

Tamoxifen gives 9.6% objective effects.

For the second line XT, weekly regimens of paclitaxel and carboplatin or docetaxel and carboplatin are more effective.

An active and relatively well tolerated regimen is the combination of gemcitabine 650 mg/m2 on days 1 and 8 and liposomal doxorubicin 30 mg/m2 on day 1. Gemcitabine can be used in combination with cisplatin and oxaliplatin.

Topotecan is used in different dose regimens: standard 5-day dose of 1.5 mg/m2/day (grade IV neutropenia is 70-80% and requires dose reduction to 1 mg/m2/day). To reduce haematological toxicity, topotecan may be supplemented with amifostine.

A weekly regimen of topotecan 4 mg/m2 on days 1.8 and 15 of a 28-day cycle is less toxic. In practice, the 15th day of administration must often be skipped. A 24-hour infusion of 8.5 mg/m2 every 3 weeks is being studied, as well as an oral form of topotecan 2.3 mg/m2 daily for 5 days every 3 weeks. Myelosuppression is lower. There are literature data on the effectiveness of irinotecan in platinum-resistant or refractory patients (250-300 mg / m2 90-minute infusion every 3 weeks.).

Efficacy in refractory cancer is: ifosfamide - 12-20%, altretamine (Hexamethylmelamine) - 12-14%, fluorouracil with calcium folinate (Leucovorin) - 10-17%, etoposide (oral) - 6-26%, epirubicin (Pharmorubicin) - 16-30%.

The effectiveness of docetaxel is 24-41%, vinorelbine - 15%, topotecan - 14-37%, irinotecan (Campto) - 21%, gemcitabine (Gemzar) - 15-28%, oxaliplatin (Eloxatin) - 29% (46% - at potentially platinum-sensitive tumors, 17% - with resistant ones), liposomal doxorubicin - 19.7%.

Several studies have demonstrated the effectiveness of thalidomide and lenalidomide either alone or in combination with other agents.

A promising new drug is trabectedin (Yondelis), isolated from the marine product Ecteinascidia turbinate and then produced synthetically, which is characterized by a unique mechanism of action.

For platinum-sensitive relapses, trabectedin 1.3 mg/m2 as a 3-hour infusion every 3 weeks. caused an objective effect in 43% of patients with a median to progression of 7.9 months.

The predominant toxicity was asthenia, neutropenia, and increased aminotransferase activity. Other studies have confirmed a 28.3% efficacy with the 1.3 mg/m2 3-hour infusion every 3 weeks regimen. and 29.6% for the regimen of 1.5 mg / m2 24-hour infusion every 3 weeks.

Efficacy, according to 3 phase II studies, was 34% with a median to progression of 5.8 months. in patients with platinum-sensitive tumors and 8% and 2.1 months. - with platinum-resistant. The combination regimen of trabectedin with doxorubicin is considered promising as a second line XT for recurrent ovarian cancer.

Bevacizumab (Avastin) 15 mg/kg IV every 3 weeks showed encouraging results. It can be used in combination with paclitaxel (3-week or weekly regimen) or with endoxan (50 mg/day orally on a long-term basis with blood counts monitored). The side effects of bevacizumab should be borne in mind, especially the risk of intestinal perforation when it is involved in the process or after irradiation of the abdominal cavity.

Therapy regimens

Monochemotherapy

Paclitaxel (Taxol) - 175-250 mg / m2 ± granulocyte colony stimulating factor (G-CSF) 3-hour IV infusion once every 3 weeks. with premedication with corticosteroids, antihistamines and H2-receptor blockers: 20 mg of dexamethasone orally or intramuscularly for 12 and 6 hours, 300 mg of cimetidine or 50 mg of ranitidine and 50 mg of diphenhydramine (diphenylhydraline hydrochloride) intravenously in a stream for 30-60 minutes before introduction. It is necessary to use special infusion systems that do not contain polyvinyl chloride (PVC).

Paclitaxel 70-80 mg / m2 in a solution of 0.9% sodium chloride or 5% glucose to a concentration of 0.3-1.2 mg / ml IV 60-minute infusion weekly for 6 weeks. or on days 1, 8 and 15 every 28 days. Premedication: dexamethasone 20 mg IV by bolus over 30 minutes, diphenhydramine 50 mg IV over 30 minutes and ranitidine 50 mg IV in 20-100 ml of 0.9% sodium chloride solution or 5% glucose 30 minutes before administration paclitaxel.

Docetaxel - 75-100 mg / m2 1-hour IV infusion 1 time in 3 weeks. with pre- and postmedication with corticosteroids: 32 mg of methylprednisolone or 8 mg of dexamethasone orally 13, 7 and 1 hour before administration and then 2 times a day for 3-4 days.

Cisplatin - 75-100 mg / m2 IV drip with hyperhydration and forced diuresis every 3 weeks.

Carboplatin - 400-450 mg/m2 IV drip once every 4 weeks. Given the significant difference in AUC and creatinine clearance in patients with normal and impaired renal function, it is recommended to calculate the dose using the Calvert formula.

Doxorubicin liposomal (Doxil, Kelix) - 40-50 mg / m2 IV infusion in 250 ml of 5% glucose for a dose of up to 90 mg and in 500 ml - for a dose of more than 90 mg every 3-4 weeks. The initial rate of administration is 1 mg / min for 10-15 minutes. In the absence of reactions, the rate is increased and the entire dose can be administered in 60 minutes.

Altretamine (Hexamethylmelamine, Hexalene) 6-8 mg/kg po daily for 21-28 days, or 65 mg/m2 po 4 times a day after meals and at bedtime daily for 14 days of a 28-day cycle (total dose per cycle - 3640 mg / m2), or 65 mg / m2 orally 4 times a day after meals and at night daily for 21 days of a 28-day cycle (total dose per cycle - 5460 mg / m2).

Oxaliplatin - 135 mg / m2 IV 2-hour infusion every 3 weeks, diluted in 5% glucose solution.

Vinorelbine (Navelbin) - 25-30 mg/m2 IV weekly for 8-10 weeks.

Gemcitabine (Gemzar) - 800-1250 mg / m2 IV on days 1, 8 and 15 of a 28-day cycle.

Topotecan -1.5 mg/m2/day IV 30-minute infusion for 5 days, or 2.3 mg/m2/day orally for 5 days, or 2.25-4 mg/m2 30-minute infusion in 50-250 ml of 0.9% sodium chloride solution or 5% glucose on days 1.8 and 15 of a 28-day cycle.

Irinotecan - 250-350 mg / m2 30-minute IV infusion once every 3 weeks; in case of diarrhea, reduce the dose to no more than 250 mg/m2.

Epirubicin (Farmorubicin) - 75-100 mg / m2 IV 1 time in 3 weeks.

Etoposide (Vepezid, Lasted) 50 mg/day orally for 21 days every 4 weeks. (total dose per cycle - 1050 mg).

5-FU + LV: leucovorin - 500 mg / m2 in 25-100 ml of 0.9% sodium chloride solution or 5% glucose IV 30-minute infusion daily on days 1-5 of a 21-day cycle. After 1 hour, 5-FU - 375 mg/m2 i.v.

Trabectedin (Yondelis) - 1.3 mg / m2 3-hour infusion or 1.5 mg / m2 24-hour infusion every 3 weeks.

Combination chemotherapy TS

Paclitaxel (Taxol) - 175 mg / m2 3-hour IV infusion with premedication.
Carboplatin - AUC 5.0-7.5 IV. Repeat cycle every 3 weeks.

Paclitaxel (Taxol) 175 mg/m2 3-hour IV infusion with premedication
Cisplatin - 75 mg/m2 intravenously with hydration. Repeat cycle every 3 weeks.
Paclitaxel (Taxol) 135 mg/m2 IV 24-hour infusion on day 1. Cisplatin - 75 mg/m2 IV on the 2nd day.

Docetaxel (Taxotere) - 75 mg/m2 on day 1 with pre- and post-medication.
Carboplatin - AUC 6 IV or cisplatin - 75 mg/m2 IV on day 1. Repeat cycle after 3 weeks.

Cisplatin - 75 mg/m2 on day 1 or 20 mg/m2/day for 5 days.
Cyclophosphamide - 600-750 mg / m2 on the 1st day. Repeat cycle after 3 weeks.

Cyclophosphamide - 600 mg / m2 IV on the 1st day.
Carboplatin - AUC 5-6 IV on day 1. Repetition of the cycle after 3-4 weeks.

Cisplatin - 75 mg/m2 IV on the 1st day.
Doxorubicin - 40-50 mg/m2 IV on the 1st day.
Cyclophosphamide - 600 mg / m2 IV on the 1st day. Repeat cycle after 3 weeks.

Ifosfamide - 3000-4000 mg/m2 IV (+ mesna) on day 1 or 1500 mg/m2 IV on days 1-5 (+ mesna).
Cisplatin - 60 mg/m2 IV on the 1st day. Repeat cycle every 4 weeks.

Gemcitabine (Gemzar) - 1000 mg/m2 IV on days 1, 8 and 15.
Cisplatin - 75 mg / m2 on the 1st or 8th day. Repeat cycle after 2 weeks.
Gemcitabine - 750 mg/m2 IV on days 1 and 8. Cisplatin - 30 mg/m2 IV on days 1 and 8. Repeat cycle every 21 days.
Gemcitabine - 650 mg/m2 IV on days 1 and 8.
Liposomal doxorubicin - 30 mg/m2 IV on the 1st day. Repeat cycle every 21 days.

Vinorelbine (Navelbin) - 25 mg/m2 IV on days 1 and 8.
Cisplatin - 75 mg/m2 IV on days 1 or 8. Repeat cycle every 21 days.
Liposomal doxorubicin (Doxil, Kelix) - 30 mg / m2 90-minute infusion, then Trabectedin - 1.1 mg / m2 3-hour infusion. Repeat cycle every 3 weeks.

In the treatment of exudative pleurisy and ascites, platinum derivatives are effective, as well as the following drugs administered intraperitoneally or intrapleurally after exudate evacuation: thiotepa - 20-40 mg, fluorouracil - 0.75-1 g (or a combination thereof), bleomycin - 30-60 mg , mitoxantrone - 25-50 mg. A large dose of thiotepa, 60-100 mg, can also be administered intramuscularly. Effective intravenous administration of cisplatin (100-200 mg in 200-1000 ml of saline with intravenous hydration) or carboplatin (600-750 mg), as well as IFN-a2, 5-50 million units.

Stromal and germ cell tumors of the ovaries

These tumors account for 5 to 10% of all malignant ovarian tumors.

They can be divided into three groups:

Ovarian stromal tumors are associated with increased estrogen secretion and concomitant endometrial cancer in 7.8% of patients. 43% of tumors are thecacellular, 24% are granulosa cells, and 33% are mixed theca and granulosa cells. The worst prognosis for granulosa cell tumors with metastases. In the case of residual tumors after surgery, radiation therapy is used at a dose of 50-60 Gy to the pelvic area. For widespread metastases, alkylating agents, doxorubicin, a combination of PVB, and combinations used in ovarian cancer are used.

Experience in the treatment of Sertoli/Leydigo cell tumors is limited due to their rarity. The efficacy of combinations of VAC (vincristine, dactinomycin, cyclophosphamide) and CAP (cyclophosphamide + doxorubicin + cisplatin) has been described.

In malignant mixed ovarian tumors, tumor size and histological structure are the main factors that determine the prognosis. The prognosis is generally poor in large tumors in which more than Y3 are elements of an endodermal sinus tumor, choriocarcinoma, or grade III immature teratoma.

For germ cell tumors, which most often occur in adolescence and adolescence, the operation of choice for lesions of one ovary is unilateral ovariosalpingectomy and biopsy of the second ovary. With bilateral lesions, a panhysterectomy is performed.

Many tumors produce proteins and enzymes that can be detected in serum as tumor markers: alphafetoprotein (AFP), chorionic gonadotropin (CG), lactate dehydrogenase (LDH).

5-year survival depends on the stage: at stage 1C - 100%, stage II - 85%, stage III - 79%, stage IV - 71%.

For dysgerminomas less than 10 cm in diameter without disruption of the capsule and invasion of other organs and without ascites, the 10-year survival rate after conservative surgery was 88.6% in one series of studies; at the same time, many women had one or more normal pregnancies that ended in childbirth after unilateral ovariosalpingectomy. Even in the case of non-radical operations after subsequent chemotherapy according to the BEP or PVB scheme, good long-term results are possible.

All patients, except those with stage I and grade I (G1) immature teratoma and stage IA dysgerminoma, require postoperative XT.

Patients after operations with incomplete removal of tumors (cytoreductive) also undergo 3-4 courses of XT according to the BEP or PVB scheme (Table 9.27).

In patients with multiple extraperitoneal lesions or who are not subject to surgical treatment due to their general condition, chemotherapy is performed at the first stage of treatment. Patients who do not respond to the BEP regimen receive XT as a second line under the VAC or VIP regimen. The issue of a subsequent operation is decided after a thorough examination and control of the level of markers.

Combination XT includes a set of drugs and treatment regimens used for testicular germ cell tumors. In order to reduce the pulmonary toxicity of bleomycin for young patients, some modification of the treatment regimens according to the PVB and BEP regimens has been proposed.

Can carboplatin replace cisplatin in the combinations used? Carboplatin is associated with less oto- and neurotoxicity. For many tumors, but not all, carboplatin can replace cisplatin without compromising efficacy. However, this does not apply to testicular germ cell tumors. In ovarian germ cell tumors, carboplatin may be a substitute for cisplatin.

In the treatment of children with extracranial germ cell tumors, 5-year survival and recurrence-free survival were 91% and 88%, respectively, when using a combination of carboplatin, etoposide, and bleomycin.

Therapy regimens

First line chemotherapy regimens

Bleomycin - 30 mg IV or IM once a week for 12 weeks.
Etoposide (VP-16) - 100 mg/m2 IV drip daily on days 1-5.

PVB or UVS

Vinblastine - 3 mg/m2 IV on days 1 and 2.
Bleomycin - 15 mg / m2 (maximum 20 mg) continuous IV 24-hour infusion daily on days 1-3.
Cisplatin - 20 mg/m2 IV drip on days 4-8. Repeat cycles every 3 weeks.

Etoposide (Vepezid) - 100 mg/m2 IV drip on days 1-3.

Cisplatin - 20 mg/m2 intravenously daily on days 1-5. Repeat cycles every 3 weeks.

Etoposide (Vepezid) - 100 mg/m2 IV drip on days 1-3.
Ifosfamide - 1500 mg / m2 intravenously daily on the 1-5th day with mass in the standard mode.

Vinblastine - 0.11 mg/m2/day IV on days 1 and 2.
Ifosfamide - 1200 mg/m2/day IV on days 1-5.
Cisplatin - 25 mg/m2/day IV on days 1-5.

Paclitaxel (Taxol) 250 mg/m2 IV 24-hour infusion on day 1
Ifosfamide - 1500 mg/m2/day IV on days 2-6.
Cisplatin - 20 mg/m2/day IV on days 2-6.
Carboplatin - 600 mg/m2 IV on the 2nd day.
Etoposide - 1 20 mg/m2 IV on days 1-3.
Bleomycin - 15 mg/m2 IV on the 3rd day. Repetition of cycles every 3-4 weeks.

Second line chemotherapy regimens

VAC (vincristine, dactinomycin, cyclophosphamide)

For immature grade II and III teratomas, a VAC regimen or similar combination with vinblastine is considered best: Vinblastine 3 mg/m2 IV on days 1 and 2. Dactinomycin - 0.5 mg/m2 IV on days 1-3. Cyclophosphamide - 800 mg / m2 IV on the 3rd day.

V.A. Gorbunova

(Moscow, 2003) ACCORDING TO THE MATERIALS OF ASCO CONGRESS 2002 (ORLANDO, USA)

Bychkov M. B.

In the materials of the ASCO-2002 congress, lung cancer took a leading place. On this issue, 314 papers are presented, which discuss various issues of epidemiology, diagnosis, morphology and treatment of both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). One work is devoted separately to bronchioloalveolar cancer and carcinoids. Various schemes and regimens of treatment of both I and II lines of treatment for NSCLC and SCLC, the effectiveness of combined chemotherapy using Taxol, Taxotere, gemcitabine, Navelbin and other new cytostatics were studied. Several papers address the issues of neoadjuvant chemotherapy and chemoradiotherapy for NSCLC and SCLC.

Particular attention was paid to the problem of molecular biological features of lung cancer and the development of methods for molecularly targeted (targeted) therapy.

NSCLC is characterized by the presence or overexpression of the epidermal growth factor receptor (EGRF), so EGRF is a promising target in the treatment of NSCLC. An EGRF-targeted monoclonal antibody (IMC-C225) has shown promising results in head and neck tumors when combined with radiation therapy or cisplatin, and many EGRF tyrosine kinase inhibitors are currently under research. Of these, only Iressa, OSI-774, PD-183805 and PK1-166 are in clinical trials. These drugs in preclinical studies in combination with cytostatics or radiation therapy have shown an additive or synergistic effect. This was the basis for conducting phase III clinical trials with the inclusion of patients with NSCLC. Early advances in NSCLC by blocking EGRF and interrupting intracellular signals should lead to the establishment of the first targeted therapy for this disease.

Kris M. et al. (abs. 1166) presented data from several US medical centers on phase II clinical trials of Iressa (ZD1839) in advanced NSCLC in patients with progression of the process after platinum- and Taxotere-containing chemotherapy regimens (study Ideal-2). Iressa is an oral, selective EGRF tyrosine kinase inhibitor that blocks signaling pathways involved in cancer cell proliferation and survival. 216 patients with locally advanced or metastatic NSCLC were treated. 102 patients received Iressa 250 mg per day, and 114 patients received 500 mg each. The effect was achieved in 11.8% and 8.8%, respectively. The effect lasted from 3 to 7+ months. 31% and 27% of patients had stabilization of the process, and 43% and 35% (respectively) showed symptomatic improvement. In 60% of patients, the symptomatic effect was achieved at 2 weeks of treatment. The median survival in both groups was 6.1 and 6.0 months. respectively. Side effects were moderate: diarrhea and skin rash I-II Art. and III-IV Art. toxicity was observed only in 6.9 and 17.5% of patients, respectively. The authors conclude that in this group of patients with a large spread of the process, Iressa showed clinically significant antitumor activity with an acceptable, quite satisfactory side effect profile.

Bissett D. (abs. 1183) with numerous co-authors from the UK, Canada, USA and Germany reported the results of phase III clinical trials of primomastat (AG3340), a matrix metallopreinase (MMP) inhibitor, in combination with gemcitabine and cisplatin as the first line of treatment for common III-B (T4) and IV Art. NSCLC. Patients were randomized: I gr. received primomastat - 15 mg 2 times a day orally, and II - placebo. Patients of both groups were also treated with gemcitabine - 1250 mg/m 2 1, 8 days and cisplatin - 75 mg/m 2 on day 1, 1 time in 3 weeks. Toxicity was manifested in the "muscle-bone" effect (MK), presumably due to inhibition of MMPs. The second and higher degrees of MK toxicity were observed in 40% in 1 gr. and 16% - in gr. placebo, and were expressed in arthralgia, myalgia, limited joint mobility and swelling. These phenomena lasted 3 weeks or more and subsided after a break in taking the drug and reducing the dose. A break was necessary in 37% of I gr. and 12% - in II gr. Median survival was 11.5 and 10.8 months. (p = 0.82), one-year survival 43% and 38%, progression-free survival 6.1 and 5.5 months, and overall efficiency 25% and 24%, respectively. The authors concluded that the addition of an MMP inhibitor did not increase the antitumor activity of the gemcitabine + cisplatin regimen in patients with advanced NSCLC.

Patel J. D. et al. in the USA (abs. 1218) studied the long-term results of treatment with trastuzumab + either Taxotere or Taxol in patients with advanced NSCLC, depending on the expression of HER-2. A randomized phase II clinical trial was conducted in untreated patients with NSCLC. 57 patients were treated, of which 13 (22%) were HER-2 positive and 44 (77%) were HER-2 negative. Overall efficacy and toxicity were similar in the Taxotere or Taxol groups, with no significant differences based on HER-2 stratification. At 12 months The median and 1-year survival for HER-2+ was 14 months and for HER-2 was 19 months. The authors concluded that 1) trastuzumab in combination with weekly taxanes showed excellent median survival and 1-year survival; 2) the contribution of trastuzumab to the survival data of each population remains unclear; 3) patients treated according to the same scheme with HER-2 + had more unfavorable characteristics and shorter survival. If these differences in survival are confirmed by multivariate analysis, then the presence or absence of HER-2 expression should be measured in future randomized trials in NSCLC.

Johnson B. E. et al. (abs. 1171) studied the efficacy of Glivec in patients with SCLC. They conducted a phase II clinical study of the drug in 19 patients (9 people received Glivec as I line, and 10 people - II line of treatment, but in sensitive patients with an effect that lasted more than 60 days). The first task was to evaluate the objective improvement at the 600 mg daily dose. No objective effect was obtained, the six-month survival rate was 68%. The authors conclude that there were few SCLC patients with Kit + (CD 117) and that further study of Gleevec as monochemotherapy in SCLC will focus on patients with the presence of a molecular target with Kit + (CD 117).

Read W. L et al. (USA) (abs. 1267) provide a large review of the epidemiology of bronchiolo-alveolar cancer (BAC) over the past 20 years since 1979 for every 5 years. Thus, with an increase in the number of patients with NSCLC - from 1979 to 1998. 1.8 times, the number of patients with adenocarcinoma (without BAD) increased by 6.8% (from 28.6% to 35.4%), and the percentage of patients with BAD over the years was almost the same (3.3% in 1979 -1983, 2.8% - in 1984-1988 and 3.8% - in 1994-1998). BAR in relation to the total number of patients with NSCLC was 3.4%, while the average age of patients with BAD was the same as for all patients with NSCLC (67.1 and 67.2 years), slightly exceeding the age of patients with adenocarcinoma (without BAD) - 65, 4 years. Among women with NSCLC, the percentage of patients with squamous cell carcinoma was 36.8%, with adenocarcinoma (without BAD) - 44%, and with BAD - 53.8%, i.e. almost 2 times more than with squamous cell carcinoma. The 1-year survival rate was the lowest in large cell cancer - 32%, and in BAD - 64.9%.

Wirth L.I. et al. (abs. 1293) studied the problem of lung carcinoids and their sensitivity to chemotherapy. 93 patients received EP or CAV chemotherapy. According to the morphological picture, all carcinoids were divided into: I - typical carcinoid, II - atypical carcinoid, III - large cell neuroendocrine carcinoma and IV - small cell carcinoma. The effectiveness of chemotherapy was evaluated in the first 2 groups and amounted to 31%. 10-year survival was assessed in all 4 groups and was in group I. - more than 80%, in II gr. - 35-56%, a III and IV gr. - less than 10%.

Combined chemotherapy for NSCLC.

Schiller I. H. (USA) presented an analysis of ECOG trials from 1980 to 2000. comparison of long-term results and characterization of patients with advanced NSCLC treated with various chemotherapy regimens. In the analysis, the author included 3398 patients divided into 2 groups: in group I. treated before 1990 (1574 people), and in II - after 1990 (i.e., treated with new cytostatics - taxanes, gemcitabine, navelbin, etc.) - 1824 people. Median survival in I gr. was 5, 9 months., and in II gr. - 8.1 months, i.e. increased by 1.4 times. Time to progression in I gr. was 2.7 months, and in II gr. 3.5, i.e. also increased by 1.3 times. The time interval from the beginning of progression to death in the I gr. was 2.7 months, and in II gr. - 4.1 months (also increased by 1.6 times). The author also cites some other characteristics that have changed over the years. So before 1990, weight loss in patients over 10 kg was in 15.4% of patients, and after 1990, only 11.9%. The number of patients with more than 1 metastasis in II gr. decreased by 2 times (45.3 and 22.8%, respectively), and the intervals from the moment of diagnosis to the start of treatment decreased from 1.4 months. up to 1 month

Raftopoulos H. et al. (abs. 1284) conducted a retrospective analysis of randomized clinical trials over 10 years from 1991 to 2001. to determine the role of chemotherapy in advanced NSCLC. The study was subjected to 8468 patients. The median survival was the lowest in the group of 783 patients treated with cisplatin alone - 7.2 months, in the group of 509 patients treated according to the cisplatin + etoposide regimen, it was 7.8 months, and the highest median survival was in the group of patients treated with cisplatin with new cytostatics - 9.2 months.

Baggstrom M. Q. et al. (USA) (abs. 1222) conducted a meta-analysis of the published literature on the effect of various chemotherapy regimens as 1st line of treatment on the survival of patients with stage III-IV. NSCLC. The authors noted that the III generation of modern chemotherapy - a combination of platinum drugs with taxanes, gemcitabine, Navelbin increases the number of objective effects by 13% (p=0.001) and median survival by 4% (p=0.001) compared with the II generation of combined chemotherapy ( combination of platinum drugs with other cytostatics). To conduct this meta-analysis, the authors used 8 large clinical trials, which included 3296 patients with NSCLC.

Massarelli E. (abs. 1223) et al. conducted a retrospective analysis of the long-term results of treatment in various clinics in the US and the UK in patients who had previously received 2 chemotherapy regimens, including platinum derivatives and Taxotere, for recurrent NSCLC. An objective effect was noted in 21% of patients after the 1st line of treatment, 16.3% after the 2nd line, and after the 3rd and 4th lines of treatment, when gemcitabine was used and combinations with other drugs, an objective improvement was noted only in 2.3% to 0%. Disease control (OE+ stab.) after the 1st line was achieved in 62.8% of patients, and after the 3rd and 4th lines - only in 21.4%. Overall 1-year survival for all lines of chemotherapy was 81.2% and 2-year survival was 18.7%. The authors conclude that the 2nd line of NSCLC treatment is of low efficiency and the 3rd and 4th lines of treatment are minimally effective, which requires further development of new chemotherapy regimens for the 2nd and other lines of NSCLC treatment.

Rudd R. M. et al. (abs. 1170) conducted a phase III clinical trial in the UK comparing the GC regimen (gemcitabine + carboplatin) with the MIP regimen (mitomycin + ifosfamide + cisplatin). The study included 422 patients with advanced NSCLC. In I gr. gemcitabine was administered at a dose of 1200 mg/m 2 on days 1 and 8, and carboplatin AUC-5 on day 1 once every 3 weeks (212 people). In II gr. (210 people) mitomycin was administered at a dose of 6 mg/m 2 , ifosfamide 3.0 g/m 2 , cisplatin 50 mg/m 2 on day 1, 1 time in 3 weeks. The number of treatment courses in both groups was 4, the authors did not note a difference in both groups in terms of the number of effects (37% in group I and 40% in group II), however, the median survival was statistically significantly higher in group I. - 10 months compared to group II. - 6.5 months In addition, in I gr. only 14% of the courses required hospitalization, and in the II group - 89% of the courses. Nausea, vomiting and alopecia were also statistically less in group I.

The results of phase II clinical trials of SWOG for the treatment of patients with stage III. NSCLC with a poor prognosis was presented by Davis A. M. et al. (USA) (abs. 1191). They administered concomitant chemotherapy with carboplatin and etoposide and radiotherapy followed by Taxol for consolidation. Carboplatin was administered at 200 mg/m 2 on days 1, 3, 29, 31, etoposide 50 mg/m 2 from days 1 to 4 and from days 29 to 32. Radiation therapy was carried out from the 1st day of treatment with a single dose of 1.8-2 Gy, a total of 61 Gy. Taxol was administered at a dose of 175 mg/m 2 once every 3 weeks, starting on day 11 of the 3rd cycle of chemotherapy. A total of 56 patients were treated. The objective effect after chemoradiotherapy was achieved in 49%, and after treatment with Taxol it increased to 58%. The median survival was 10.3 months and the 2-year survival was 27%. Neutropenia and thrombocytopenia III-IV st. were present in 45% and 23% of patients, respectively. The authors compared the results of this study with those of their other study, which did not administer Taxol for consolidation, and noted that although this treatment regimen resulted in a 2-fold increase in the objective effect (58% and 29%), but the median survival and 2-year survival did not increase, possibly due to the high drug-induced mortality (9.2%) in the group treated with Taxol during consolidation therapy.

Kakolyris S. et al. (abs. 1182) conducted a phase III multicenter randomized trial in Greece comparing the efficacy of two chemotherapy regimens: Taxotere + gemcitabine (gr. A) and Navelbin + cisplatin (gr. B). A total of 251 patients were treated. 229 patients were subject to evaluation. In gr. A (117 people) Taxotere was administered at a dose of 100 mg/m 2 on day 8 + gemcitabine 1.0 g/m 2 on days 1 and 8, and in gr. In (102 people) - Navelbin 30 mg/m 2 on days 1 and 8 + cisplatin 80 g/m 2 on day 8, all patients received rhG-CSF - 150 μg/m 2 on days 9-15. The cycles were repeated every 3 weeks. A total of 917 cycles were performed (median 3 cycles per 1 patient). O.E. in gr. A was 29%, in gr. B -36%. Duration of effect, time to progression, and median survival were 6 months, 8 months. and 9 months. in gr. A and 6.5 months, 8.5 months. and 11.5 months. in gr. B. The authors conclude that Taxotere + gemcitabine and Navelbine + cisplatin regimens have comparable activity in patients with advanced NSCLC, but regimen II is more toxic.

Huang C. H. et al. (abs. 1347) conducted a US phase III toxicity comparison of two chemotherapy regimens carboplatin + Taxotere (or + Taxol) in advanced NSCLC. The study included 99 patients, 75 people were evaluated at the time of the report. In I gr. there were significantly fewer neuropathies (14% and 44%, p=0.002) and myalgias (8% and 31%, p=0.01), but more neutropenia (61% and 51%, p=0.390) and anemia (45 % and 38%, p=0.6) III-IV stage OE was comparable (22% and 31%, p=0.23).

Gandara D. R. et al. (abs. 1247) presented papers from a California Cancer Consortium study investigating the effect of gene level p53 on the results of treatment of patients with NSCLC. 33 patients received chemotherapy according to the scheme: gemcitabine 1000 mg/m 2 on days 1 and 8 as the 2nd line of treatment. The median progression-free survival and overall median survival in patients with p53 overexpression was almost 2 times lower than in patients without overexpression.

Taxol in combination chemotherapy for NSCLC.

A large number of works are devoted to the role of Taxol in combined chemotherapy for NSCLC. So Lilenbaum R. C. et al. (abs. 2) reported a large US randomized trial comparing the efficacy of Taxol versus Taxol plus carboplatin in 584 patients with advanced NSCLC. The objective effect was almost 2 times greater in the combination chemotherapy group (30%) compared to Taxol alone (15%) (the difference is statistically significant). There was also a significant difference in median survival (8.5 months and 6.5 months, respectively).

Belani S. R. et al. (abs. 1245) reported a comparative evaluation of 2 combination chemotherapy regimens with Taxol and gemcitabine in 53 patients with NSCLC. In 1 gr. (25 people) Taxol was administered at a dose of 200 mg/m 2 1 time in 3 weeks, and in 2 gr. (28 people) - 100 mg / m 2 1 and 8 days. Gemcitabine in both schemes was administered at 1000 mg/m 2 on days 1 and 8. The authors did not note significant differences in both groups in terms of the number of objective effects (52% and 50%), complete remissions (8% and 11%), and the number of stabilizations (36% and 43%, respectively). Neutropenia and thrombocytopenia III-IV st. was noted much more often in group 1 than in group 2 (24% and 12% in group 1 and 14.2% and 3.5% in group 2). Neurotoxicity III-IV Art. was noted only in 2 gr. (3.5%).

Suzuki R. et al. (abs. 1299) studied the efficacy of 2-line chemotherapy with Taxol administered once a week in patients with resistant or recurrent NSCLC previously treated with the combination of Taxotere and carboplatin. The authors treated 32 patients with Taxol at a dose of 80 mg/m 2 once a week for 6 weeks. 70 cycles of chemotherapy were carried out. The authors obtained an objective improvement in 17% of patients and another 43% showed stabilization of the process. Neutropenia and anemia III-IV Art. was, respectively, in 41% and 15% of patients.

Cortes J. et al. (abs. 1297) conducted an interesting study evaluating the efficacy of 1st line chemotherapy in patients with NSCLC with brain metastases. The authors treated 26 patients according to the following scheme: Taxol 135 mg/m 2 on day 1, cisplatin 120 mg/m 2 on day 1, + Navelbin 30 mg/m 2 on days 1 and 15, or gemcitabine 800 mg/m 2 on days 1 and 8 days. A total of 84 courses of treatment were carried out for patients. An objective effect was achieved in 10 out of 26 patients (38.5%), while 1 patient had complete regression of brain metastases. Radiation therapy was performed when chemotherapy was ineffective or progressed to a brain area.

And, finally, Felip E. et al. (abs. 1217) presented data on a multicenter phase II study of a new taxane analogue from Bristol-Myers Squibb, BMS-184476, as a 2nd line of chemotherapy. It was administered at a dose of 60 mg/m 2 once every 3 weeks to 56 patients with NSCLC, the number of cycles was 262. The authors noted the activity of the drug in 15.6% of patients and the stabilization of the process in 59%. Thus, control of tumor growth was achieved in 74% of patients. The authors consider this drug promising for its inclusion in various NSCLC combination chemotherapy regimens.

Taxotere in combination chemotherapy for NSCLC.

Jensen N. V. et al. (abs. 1285) conducted a Danish randomized trial comparing the combination of Taxotere + carboplatin with carboplatin alone as 1st line treatment for NSCLC. Carboplatin was administered at a dose of AUC-6 at 3-week intervals for a total of 6 cycles (1 g). The same dose of carboplatin in 2 gr. administered in combination with Taxotere 80 mg/m 2 once every 3 weeks, also 6 cycles. In total, treatment was carried out in 66 patients (33 in each group). In 1 gr. an objective effect was obtained in 12% of patients, and in 2 gr. - 36%. Median survival and 1-year survival in 1 gr. were 6.8 months. and 18%, and in 2 gr. respectively 7.9 months. and 29%. The authors note a significant advantage of combined chemotherapy (OE - 3 times higher, and one-year survival more than 1.5 times).

The same combination of Taxotere + carboplatin in advanced NSCLC was studied by Ramalingam S. et al. (USA) (abs. 1263). The objective of the study was to investigate the effect of carboplatin dose on survival. The study included 78 patients, 66 of them were evaluated. In both groups, Taxotere was administered at 80 mg/m 2 and carboplatin at 1 g. was prescribed in a dose of AUC-6 (28 patients), and in 2 gr. - AUC-5 (38 patients). The number of cycles was up to 9 in 1 gr. and up to 6 - in 2 gr. The objective effect was 46% and 29%, the median survival was 13.1 and 11.4 months. respectively. At the same time, febrile neutropenia in 1 gr. was more often - 24.2%, and in 2 gr. - 17.8%. The authors concluded that the dose of carboplatin used in combination with Taxotere affected the effectiveness of the combination.

The role of the 2nd line of chemotherapy in metastatic NSCLC was presented by van Putten J. W. G. et al. (Holland) (abs. 2667). 57 patients with III B-IV Art. NSCLC, in which progression of the disease was noted after the 1st line of treatment, with gemcitabine in combination with epirubicin or cisplatin, was treated with Taxotere at a dose of 75 mg/m 2 + carboplatin AUC-6 1 time in 3 weeks, 5 cycles, Objective effect was achieved in 37% patients, while in those previously treated with platinum-containing regimens, OE was 31%, and in those treated with non-platinum-containing regimens - 41%. The median time to progression was 17 weeks and the median survival was 31 weeks. The authors concluded that the Taxotere + carboplatin regimen is an active combination for the 2nd line of treatment in patients with advanced NSCLC who previously received gemcitabine-containing chemotherapy regimens, and does not have cross-resistance.

Gemcitabine in combination chemotherapy for NSCLC.

A large number of papers in ASCO NSCLC chemotherapy materials are devoted to gemcitabine.

Sederholm C. (abs. 1162) reported on a Phase III clinical trial conducted by the Swedish Lung Cancer Group. This is a large study that treated 332 patients with advanced NSCLC. Gemcitabine at a dose of 1250 mg/m 2 was administered on days 1 and 8 once every 3 weeks (1 g - 170 people) and compared with the same dose of gemcitabine in combination with carboplatin AUC-5 on day 1 (2 g - 162 people). Objective effect in 1 gr. was noted in 12%, and in 2 gr. - 30%. Time to progression in 2 gr. was 6 months old, and in 1 gr. - 4 months, the difference in both indicators is statistically significant. Anemia, leukopenia and thrombocytopenia III-IV Art. noted only in 2 gr. and equaled 1.5%, 12.6% and 15.2% respectively.

Manegold S. et al. (Germany) (abs. 1273) published a final report on two randomized phase II trials of monochemotherapy with gemcitabine and Taxotere administered sequentially at different doses and regimens as 1st line treatment for advanced NSCLC. In total, the study included 380 patients divided into 2 groups. In 1 gr. gemcitabine was administered at 1000 mg/m 2 on days 1, 8, 15, and Taxotere -35 mg/m 2 on the same days with a cycle repeating every 4 weeks, in 2 gr. - gemcitabine 1250 mg/m 2 on days 1 and 8, Taxotere 80 mg/m 2 on day 1 once every 3 weeks. The authors did not find a difference in the effect of gemcitabine on median survival, 6 months, 1-year and 2-year survival. Only the effect of the Taxotere regimen on the median survival was statistically significant (5 months in 1 g and 9.2 months in 2 g, p=0.002).

Kouroussis S. et al. (abs. 1212) reported the results of a multicenter phase II study of 2nd line chemotherapy in NSCLC patients previously treated with taxanes and cisplatin. The study included 135 patients. In 1 gr. patients received gemcitabine at a dose of 1000 mg / m 2 on days 1 and 8 + irinotecan 300 mg / m 2 on day 8 (71 people), and in 2 gr. (64 people) - only irinotecan at the same dose in 1 day. Objective effect in 1 gr. was achieved in 21% of patients, and in 2 gr. - 5.5%. The median time to progression was 8 months. and 5 months. Neutropenia, anemia and thrombocytopenia III-IV st. were more common in group 1 than in group 2. 26%, 9%, 9% and 20%, 0%, 3% respectively.

Novakova L. et al. (abs. 1225) reported a phase III clinical trial comparing 2 combinations of gemcitabine with cisplatin and carboplatin. The study included 63 patients with stage IIIB and stage IV. NSCLC who received 1st line of chemotherapy. Gemcitabine in both groups was administered at a dose of 1200 mg/m 2 on days 1 and 8. In 1 gr. (29 people) - cisplatin was administered at 80 mg / m 2 on day 1, and on day 2. - carboplatin AUC-5 in 1 day. Treatment courses were repeated 1 time in 3 weeks. The authors did not find any difference in both groups both in the number of objective effects (48% and 47%) and in the number of complete remissions and partial remissions (7% and 41% in group 1, and 6% and 41% in group 2). ). Anemia, leukopenia, neutropenia, thrombocytopenia were found in 23.8%, 27%, 54% and 44.4%, respectively, in both groups combined).

Japanese authors (Hosoe S. et al) (abs. 1259) presented the final report on phase II clinical trials of non-platinum triplets in patients with advanced NSCLC. 44 patients received gemcitabine 1000 mg/m 2 and Navelbin 25 mg/m 2 on days 1 and 8 (3 cycles) followed by Taxotere 60 mg/m 2 once every 3 weeks, also 3 cycles. An objective effect was obtained in 47.7% of patients, the median survival and 1-year survival were quite high (15.7 months and 59%, respectively). Leukopenia, neutropenia and thrombocytopenia III-IV st. were respectively in 36%, 22% and 2% of patients. The authors conclude that this non-platinum-containing combination chemotherapy regimen for NSCLC is well tolerated and effective.

Joppet M. et al. (USA) (abs. 2671) reported the use of a new combination for the treatment of advanced NSCLC - gemcitabine + topotecan as the 1st line of treatment. The authors treated 53 patients with stage IIIB and IV. NSCLC. Gemcitabine was administered at a dose of 1000 mg/m 2 on days 1 and 15, topotecan 1 mg/m 2 on days 1-5. An objective effect was obtained in 17% of patients and stabilization in another 23%. The median time to progression was 3.4 months. (from 1 to 15 months, duration of effect - 4.7 months. (from 2.1 to 10.8 months). 1-year survival = 37%, and median survival 7.6 months. (from 1 to 16 , 2 months).Toxicity grades III-IV were: neutropenia - 53%, anemia -18%, thrombocytopenia - 12%. lines of chemotherapy for advanced NSCLC with an acceptable toxic profile.

The combination of gemcitabine with cisplatin and with Herceptin as the 1st line of treatment for patients with advanced NSCLC with HER-2 overexpression was studied by Tran H. T. et al. (USA) (abs. 1226). They presented a final report on the treatment of 19 patients with NSCLC who received gemcitabine 1250 mg/m 2 on days 1 and 8, cisplatin 75 mg/m 2 on day 1, and Herceptin 4-2 mg/kg once a week. In 8 out of 19 patients, an objective effect (42%) was achieved, and in another 8 - stabilization. Thus, disease control was observed in 84% of patients. Data on median survival and time to progression are not presented.

Ettinger D.S. et al. (abs. 1243) studied a new combination: gemcitabine + Alimta in 54 patients with advanced NSCLC. Gemcitabine was administered at a dose of 1250 mg/m 2 on days 1 and 8, and Alimta at 500 mg/m 2 on day 8. 228 cycles of treatment were carried out. An objective effect was achieved in 17% of patients. Median time to progression was 5.1 months, median survival was 11.3 months, and 1-year survival was 46%. In 63% of patients, grade III-IV neutropenia was noted, and grade III-IV thrombocytopenia. - 7%. The authors consider it promising to further study this com-

Induction (neoaljuvant) chemotherapy for NSCLC.

Betticher D. C. et al. (abs. 1231) reported a multicentre non-randomized study on the use of induction (preoperative) chemotherapy in patients with IIIA pN2 NSCLC. 77 patients with stage NSCLC histologically proven by mediastinoscopy pN2 received Taxotere 85 mg/m 2 on day 1 + cisplatin 40-50 mg/m 2 on days 1 and 2 once every 3 weeks. 3 cycles of chemotherapy were carried out, after which, on the 22nd day after the 3rd cycle, a radical resection with mediastinal lymphadenectomy was performed. An objective effect after chemotherapy was achieved in 67% of patients, while 8% achieved complete regression. Radical resection was successful in 56% of patients, while histologically complete regression was noted in 16%. Radiation therapy at a dose of 60 Gy was performed in patients with non-radical resection. The 2-year survival rate in this group of patients was 41%. Median survival was 28 months, median progression-free survival and overall survival were 12 and 28 months. respectively. The most frequent metastases (in 13% of radically operated patients) were brain metastases, and local recurrences - in 22% of all patients.

The work of Italian authors (Cappuzzo et al) (abs. 1313) presents phase II clinical trials of the gemcitabine + cisplatin + Taxol regimen as a neoadjuvant therapy for unresectable IIIA (N2) and IIIB stage. NSCLC. Gemcitabine was administered at a dose of 1000 mg/m 2 , cisplatin 50 mg/m 2 and Taxol 125 mg/m 2 , all drugs were administered on days 1 and 8 every 3 weeks. 3 cycles were performed in 36 patients. The objective effect was very high - 72% (in 21 of 36 patients), while 2% achieved complete remission. Radical surgery was performed in all patients with an objective effect, while histologically proven complete regression was noted in 3 (8%) patients. 11 patients who did not undergo radical resection underwent radiation therapy. III-IV Art. neutropenia and thrombocytopenia were in 27% and 3%, respectively. These preliminary data indicated that this combination was well tolerated in locally advanced NSCLC.

Chemotherapy in combination with radiation therapy for NSCLC.

Kawahara M. et al. (abs. 1262) presented the final report of the Japan Clinical Oncology Group on a complex phase II study of induction chemotherapy with sequential radiotherapy in combination with weekly irinotecan in 68 patients with unresectable stage III. NSCLC. Cisplatin was administered at a dose of 80 mg/m 2 on days 1 and 29, irinotecan at a dose of 60 mg/m 2 on days 1, 8, 15, 29, 36, 43, and then during radiation therapy at a dose of 30 mg/m 2 at 57, 64, 71, 78, 85 and 92 days. Radiation therapy at a single dose of 2 Gy per day began on day 57, the total dose was 60 Gy. An objective effect was achieved in 64.7% of patients, and complete remission in 9%. The median survival was 16.5 months, 1-year survival was 65.8%, and 2-year survival was 33%. Neutropenia and esophagitis III-IV stage. were in 18% and 4%, respectively. The authors concluded that this chemotherapy regimen is effective in locally advanced NSCLC.

Zatloukal P. V. et al. (Czech Republic) (abs. 1159) conducted a randomized trial comparing simultaneous and sequential chemoradiotherapy for NSCLC. The authors compared 2 groups of patients: 52 patients (1 group) receiving radiation therapy simultaneously with chemotherapy and 50 patients (2 groups) receiving sequential radiation therapy. all patients underwent chemotherapy according to the scheme: cisplatin 80 mg/m 2 on day 1 and Navelbin 25 mg/m 2 on days 1, 8, 15. The interval between courses was 4 weeks, all patients underwent 4 courses of chemotherapy. Radiation therapy in 1 gr. began on day 4 of cycle 2 of chemotherapy (60 Gy in 30 fractions for 6 weeks). In 2 gr. radiation therapy in the same mode was started 2 weeks after the end of chemotherapy. Objective effect in 1 gr. was achieved in 80.4% of patients, and in 2 gr. - 46.8%. Complete remission was obtained in 21.6% and 17% of patients, respectively. The median survival was significantly higher in 1 g. - 619 days compared to 2 gr. - 396 days (p=0.021). The median time to progression was also statistically significantly greater at 1 hr. - 366 days compared to 2 gr. - 288 days (p=0.05). The authors believe that their data confirm the advantage of simultaneous chemoradiotherapy over sequential chemoradiotherapy both in terms of objective effect and life expectancy. The higher toxicity in the concurrent radiotherapy group is acceptable.

Combined chemotherapy for SCLC.

Japanese authors have presented several reports on the efficacy of irinotecan in SCLC. So, Kinoshita A. (abs. 1260) et al. reported the results of phase II combined chemotherapy of 60 patients with SCLC (26 with localized process and 34 with widespread) with irinotecan 50 mg/m 2 on days 1, 8 and 15 in combination with carboplatin AUC-5 on day 1 as the first line of treatment. Treatment courses were repeated 1 time in 4 weeks. O.E. was achieved in 51 patients (85%), with a localized process (LP) - in 89%, and with a widespread process (RP) - in 84%. Complete remission was observed in 28.3%, and partial - in 56.7% of patients. The median survival was 15.7 months. (18.2 months with LP and 9.7 months with RP. 1-year survival reached 55% (with LP - 88%, and with RP - 26.5%). 2-year survival was, respectively, in 29, 6%, 49.8% and 11%). Leukopenia, neutropenia and thrombocytopenia III-IV st. was in 35%, 76% and 42% of patients, respectively.

Ikuo S. et al. (abs. 1223) presented a large randomized phase II study of the effectiveness of the combination of irinotecan + cisplatin + etoposide administered weekly or once every 4 weeks in 60 patients with RCLC. In group I, irinotecan was administered at a dose of 90 mg/m 2 at 1, 3, 5, 7, 9 weeks of treatment, cisplatin - 25 mg/m 2 weekly for 9 weeks, etoposide was administered at 60 mg/m 2 at 1-3 days at 2, 4, 6, 8 weeks of treatment. In group II, irinotecan was administered at 60 mg/m 2 on days 1, 8, 15, cisplatin - 60 mg/m 2 on day 1, etoposide - 50 mg/m 2 on days 1-3. Courses of treatment in II gr. repeated once every 4 weeks. Each group included 30 patients. O.E. was almost the same: in group I - in 84%, and in group II - in 87%. However, in II gr. PR was achieved in 17% in group II. and only 7% - in I gr. Median survival and 1-year survival were also higher in group II. (13.8 months and 56% compared with 8.9 months and 40% in group I). Neutropenia and thrombocytopenia III-IV st. were 57% and 27% of patients in group I, and in 87% and 10% - in group II. Diarrhea III-IV Art. was almost the same in both groups (in 7% and 10%). The authors conclude that the II scheme of combined chemotherapy is more effective and plan to use it in further scientific developments.

Niell H. B. et al. (abs. 1169) presented data from a large randomized trial comparing etoposide plus cisplatin (EP) with or without Taxol in 587 patients with advanced SCLC. In group I (294 patients), etoposide was administered at 80 mg/m 2 for 1-3 days and cisplatin at the same dose once every 3 weeks. In group II, Taxol -175 mg/m 2 on day 1 and G-CSF 5 μg/kg on days 4-18 of each cycle were added to the same chemotherapy regimen. Median survival and 1-year survival in group I were 9.85 months. and 35.7%, and in II gr. - respectively 10.3 months. and 36.2%. Toxicity in the >lll grade groups was: neutropenia - 63% and 44%, thrombocytopenia -11 and 21%, anemia - 15 and 18%, neurological - 10 and 25%, and general toxicity in 84% and 77%, grade V toxicity (drug death) was in 2.7% and 6.4%, respectively. The authors conclude that adding Taxol to an EP regimen as initial therapy for advanced SCLC increases grade V toxicity without affecting survival.

Dunphy F. et al. (abs. 1184) provides data from the phase II clinical trial SWOG-9914 on the effectiveness of the combination of Taxol + carboplatin + topotecan (PCT regimen) in advanced SCLC as the first line of treatment. This is a randomized study conducted in the USA, which involved 86 patients with SCLC. Treatment regimen: Taxol -175 mg/m 2 on day 4, carboplatin AUC-5 on day 4 and topotecan 1.0 mg/m 2 days 1-4 with G-CSF 5 mcg/kg from day 5 until increase in absolute neutrophil count > 10000. Treatment was carried out 1 time in 3 weeks, only 6 cycles. The median survival was 12 months, the median to progression was 7 months, and the 1-year survival rate was 50%. The authors compared these results (historical control) with two other chemotherapy regimens PET (Taxol + cisplatin + etoposide) and GE (gemcitabine + cisplatin) in 88 patients in each group. Median survival, median time to progression, and 1-year survival were, respectively, 11 months, 6 months, and 43% in the PET group and 9 months, 5 months, and 28% in the group. G.E. Toxicity IV Art. in the PCT group was 33%, PET - 39%, GE - 27%. The authors believe that the comparison of PCT, PET, and GE regimens indicates a favorable median survival and median to progression of the PCT regimen without increasing toxicity, as well as a pronounced increase in 1-year survival in this group of patients with SCLC, which gives some hope.

A comparison of two combination chemotherapy regimens in SCLC patients with a poor prognosis was carried out by James L. E. et al. (abs. 1170) in the UK. This was a phase III randomized clinical trial comparing the efficacy of the gemcitabine + carboplatin (GC) regimen with the standard PE regimen (etoposide + cisplatin). The treatment was carried out in 241 patients (120 in group I and 121 in group II). GC scheme: gemcitabine 1, 2 g/m 2 on days 1 and 8, carboplatin AUC-5 on day 1 once every 3 weeks, 4-6 courses. PE scheme: cisplatin 60 mg/m 2 on day 1, etoposide 120 mg/m 2 on days 1-3, also once every 3 weeks, 4-6 courses. O.E. in I gr. - 58%, in II gr. - 63%, median survival 8.1 months and 8.2 months. respectively. Ill and IV Art. toxicity was as follows: anemia 3% and 1%, leukopenia 5% and 1%, neutropenia 11% and 9%, thrombocytopenia 5% and 1%. The results of the study confirmed that the GC regimen had more hematological but less non-hematological toxicity than the standard PE regimen and resulted in good survival.

De Marinis F. et al. (abs. 1219) conducted a multicentre, randomized, phase II trial in Italy comparing gemcitabine + cisplatin + etoposide (PEG) versus gemcitabine + cisplatin (PG) as the first line of treatment for SCLC. PEG scheme: cisplatin 70 mg/m 2 on day 2, etoposide 50 mg/m 2 on days 1-3, gemcitabine 1.0 mg/m 2 on days 1 and 8. The intervals between courses were 3 weeks, 62 patients were treated, the number of treatment cycles was 207 (median 4 cycles). Scheme PG: cisplatin 70 mg/m 2 on day 2, gemcitabine 1.2 g/m 2 on days 1 and 8, intervals of 3 weeks, number of patients - 60, number of cycles - 178 (median 3 cycles). O.E. in gr. PEG obtained in 69%, and gr. PG - in 70%, while complete remission was observed in 25% and 4%, respectively (p=0.0001). With localized SCLC O.E. was in 70% and 80%, and with widespread in 68% and 59%, respectively. Toxicity III-IV stage: leukopenia -14% and 4%, neutropenia - 44% and 24%, anemia -16% and 8%, thrombocytopenia - 42% and 26%. The authors note that both PEG and PG regimens are active and well tolerated in the treatment of patients with SCLC. At the same time, the triplet leads to a greater number of III-IV st. toxicity (not statistically significant) and greater activity of patients. Despite this, among combinations with "new" drugs, the PEG and PG regimens seem to be less toxic and have similar activity.

Jett J. R. et al. (abs. 1301) used oral topotecan in combination with Taxol and G-CSF support in patients with untreated advanced SCLC. 38 patients received oral topotecan at a dose of 1.75 mg / m 2 for 5 consecutive days, Taxol -175 mg / m 2 on day 5, G-CSF starting from day 6, intervals between courses - 28 days, a total of 4-6 treatment cycles . O.E. was achieved in 17 patients (45%), while PR was in 3, and PR was in 14 people. Median survival was 8.6 months, median time to progression was 5 months, and 1-year survival was 43%. The authors consider that oral topotecan in combination with Taxol is an active regimen for advanced SCLC, but may not improve standard treatment outcomes. The toxicity of this regimen was moderate. It is planned to continue studying the oral form of topotecan in combination with other cytostatics.

In localized SCLC, chemoradiotherapy is being explored using various combination chemotherapy regimens and various radiotherapy (RT) regimens.

So Gray J. R. et al. (abs. 1189) conducted phase II clinical trials in the USA of Taxol + carboplatin + topotecan in combination with simultaneous RT in the treatment of localized SCLC (LP SCLC) as the first line of treatment. Treatment regimen: Taxol 135 mg/m 2 on day 1, carboplatin AUC-5 on day 1, topotecan 0.75 mg/m 2 on days 1-3, intervals between courses - 3 weeks, a total of 4 courses of XT. RT started simultaneously with cycle III XT at a single dose of 1.8 Gy. daily 5 times a week, DM=61.2 Gy. The treatment was carried out in 78 patients, 68 of them completed the full cycle of treatment. Thirty-five of 68 patients achieved complete remission (51%). Within 1 year, 65% of patients were without signs of illness. The median survival was 20 months and the 1-year survival was 64%. III-IV Art. toxicity: leukopenia -60%, thrombocytopenia -42%, hospitalization with neutropenic fever -14%, fatigue -14%, esophagitis 8%, pneumonitis -1%. 3 patients died from drug toxicity (radiation pulmonitis -2, pneumonia - neutropenia -1). The authors conclude that the use of this triplet in combination with 61.2 Gy of RT is a possible treatment for good PS in patients with LA SCLC and leads to a high number of complete remissions.

Belderbos J. et al. (abs. 1300) also conducted a study in the Netherlands to evaluate the effectiveness of combined XT and early RT in patients with LPSCLC.

Treatment regimen: chemotherapy CTE-carboplatin AUC-6 on day 1, Taxol 200 mg/m 2 on day 1, etoposide 100 mg/m 2 on day 1-5, courses of treatment 1 time in 3 weeks, 4 courses in total. LT - 1.8 Gy per day starting from day 3 of the 2nd course XT, total dose of LT-45 Gy. Upon reaching the PR, prophylactic brain irradiation (POI) was carried out in SD-30 Gr. The treatment was carried out in 26 patients, the number of courses of XT - 98. The objective effect was obtained in 24 people. (92%), PR was achieved in 38% of patients. The median survival was 19.7 months. Brain metastases were detected after treatment in 15% of patients. Toxicity III-IV stage: neutropenia - 70%, thrombocytopenia - 35%, esophagitis -27%. The authors concluded that the CTE regimen with early radiation therapy is active in LPSLC, but has a pronounced hematological toxicity. Early irradiation of the primary tumor and regional lymph nodes is safe, but the timing of POM should be specified.

Mori K. et al. (abs. 1173) reported combined chemoradiotherapy for SCLC followed by irinotecan and cisplatin. The authors treated 31 patients with LCLC according to the scheme cisplatin 80 mg/m 2 on day 1, + etoposide 100 mg/m 2 on days 1-3. Radiation therapy was carried out at 1.5 Gy. 2 times a day for 3 weeks in a total dose of 45 Gy. From the 29th day of treatment, patients were administered irinotecan 60 mg/m 2 on days 1, 8, 15 in combination with cisplatin 60 mg/m 2 once every 4 weeks, for a total of 3 cycles. An objective effect was achieved in 29 out of 30 patients who completed treatment (96.6%), while 11 people achieved complete remission (36.6%). 1-year survival was also very high - 79.3% for those treated according to the main protocol (25 people) and 87.5% for those who also received irinotecan + cisplatin. III-IV Art. toxicity during chemotherapy SR was as follows: leukopenia 48% and 12%, thrombocytopenia - 4% and 0%, anemia - 44% and 0%, diarrhea - 4% and 4%. The authors conclude that CP chemotherapy with simultaneous RT twice daily followed by 3 cycles of IP is a safe and active treatment modality with an encouraging 1-year survival. It is planned to conduct phase III clinical trials using this treatment regimen.

Roof K.S. et al. (abs. 1303) conducted a retrospective analysis of radiation dose escalation in localized SCLC based on materials from the US Massachusetts Hospital for the period 1990-2000. Patients were divided into 2 groups I - received 50-54 Gy, II - more than 54 Gy. Median overall survival was 41 months, 2- and 3-year survival rates were 61% and 50%, respectively. Disease-free survival, local control, and absence of distant metastases at 3 years of follow-up were 47%, 76%, and 69%, respectively. There were no significant differences in these parameters in both dose groups. Toxicity >3 tbsp. was also similar in both groups. There were 5 treatment-related deaths: 3 due to neutropenia, 2 due to pulmonary fibrosis, with 4 deaths in group II. And although the authors did not reveal significant differences in long-term results and toxicity in both groups, they consider it justified to conduct phase III prospective randomized trials to assess dose escalation in localized SCLC.

An interesting study was reported by Videtic G. M. M. et al. (abs. 1176), who presented materials from clinics in the USA, England and Canada on the study of the survival of patients with localized SCLC, depending on smoking during chemoradiotherapy.

The authors observed 293 patients with SCLC who received CAV->EP chemotherapy and radiation therapy - 40 Gy. I gr. -186 people - patients who smoked during treatment, and II gr. -107 people - non-smokers, 2-year survival in group I was 16%, and in 11-28%, 5-year - 4% and 8.9%, and the median survival was 13.6 months. and 18 months respectively. The 2- and 5-year disease-free survival rates were -18% and 5% for smokers and 32% and 18% for non-smokers. A decrease in survival by 2 or more times among patients who continued to smoke during chemoradiation therapy, compared with non-smokers, was also accompanied by lower survival rates without signs of disease in smokers (2-year - 18%, 5-year - 7%), according to compared with non-smokers (32% and 18%, respectively). At the same time, the authors note that the tolerability of treatment in both groups was almost the same.

All papers used in this review are published in Program/Proceedings ASCO, vol. 21, 2002, references to them are given in the text.

References for this article are provided.
Please, introduce yourself.

Table 3 14-day PCT option according to the schemeCMF

	A drug	Single dose	Route of administration	Introduction days
	Cyclophos-famid			Daily but from 1st to 14th
	Methotrexate
	5-fluorouracil
The courses of treatment are repeated every 4 weeks (the course is repeated on the 29th day, i.e. the interval between courses is 2 weeks). 6 courses.

For patients older than 60 years, the dose of methotrexate is 30 mg / m 2, 5-fluorouracil - 400 mg / m 2.

therapy in order to prevent the possible development of post-therapeutic changes.

Before starting treatment, catheterization of a peripheral or central vein is performed. The most rational is hardware infusion.

PCT with anthracycline-containing derivatives (doxorubicin, epirubicin) is recommended for breast cancer patients with a poor prognosis. 4 courses.

In case of metastatic lesions of 4 or more regional lymph nodes, 4 courses of PCT are performed according to the EU scheme and then 3 courses of PCT according to the CMF scheme.

Conducting PCT according to the scheme cap:

cyclophosphamide 500 mg/m 2 intravenously on day 1;

doxorubicin 50 mg/m 2 intravenously on day 1;

5-fluorouracil 500 mg/m 2 intravenously on the 1st day.

Interval 3 weeks.

Patients with breast cancer with an unfavorable prognosis, who have a pathology of the cardiovascular system, undergo chemotherapy regimens with epirubicin.

Carrying out PCT according to the EU scheme:

- epirubicin 60-90 mg/m 2 intravenously on day 1;

Cyclophosphamide 600 mg/m 2 intravenously on the 1st day.
Interval 3 weeks. 4 courses.

Carrying out PCT according to the AC scheme:

doxorubicin 60 mg/m 2 intravenously on day 1;

cyclophosphamide 600 mg/m 2 intravenously on the 1st day.
Interval 3 weeks. 4 courses.

HORMONOTHERAPY

In premenopausal women with 8 or more metastatic lymph nodes after completing 6 courses of chemotherapy and continuing menstrual function, bilateral oophorectomy is indicated, followed by the appointment of tamoxifen 20 mg per day for 5 years. At

cessation of menstrual function after 6 courses of PCT, tamoxifen is prescribed at 20 mg per day for 5 years.

All patients with stage III postmenopausal breast cancer with a positive hormone receptor status of the tumor after combined and complex treatment are recommended to take tamoxifen at a dose of 20 mg per day as adjuvant hormone therapy for 5 years.

IVstage

Treatment of patients with preserved ovarian function.

Patients with breast cancer with an ulcerated tumor, complicated by infection, bleeding, undergo a palliative mastectomy for sanitary purposes. Treatment is complemented by chemoradiation. hormone therapy.

Patients with preserved ovarian function undergo bilateral oophorectomy followed by the appointment of tamoxifen 20 mg per day for 5 years or until progression after treatment. After the end of the effect of tamoxifen, hormone therapy of the second, third line (medroxyprogesterone acetate, anastrozole, exemestane, letrozole) is prescribed, and then courses of PCT are prescribed.

The appointment of other types of special treatment depends on the localization of metastases.

1. In case of cancer with metastases in the contralateral supraclavicular and cervical lymph nodes:

Radiation therapy: the entire mammary gland and all areas of regional metastasis (supraclavicular-axillary and parasternal, if necessary - cervical lymph nodes) are irradiated. All zones are supplied with ROD 4 Gy, SOD 28 Gy (equivalent to a dose of 40 Gy in the traditional mode of fractionation). After two to three weeks, radiation therapy continues in the traditional dose fractionation regimen (ROD 2 Gy) up to SOD 30 Gy. For the entire course of treatment, SOD is equivalent to 60 Gy. Possibly local (from the sighting field.

corresponding to the size of the residual tumor of the breast) additional dose increase to SOD. equivalent to 80 Gr.

6 courses of PCT according to the CMF or CAP scheme.

In menopause, hormone therapy (antiestrogens) is added.

Sometimes a palliative mastectomy is performed to
improving the efficiency of PCT (with significant amounts
tumors).

2. In case of cancer with metastases in other organs, as a rule, systemic therapy (chemohormonal) is carried out.

Simultaneously with hormonal treatment, in the presence of metastatic bone lesions with severe pain syndrome, palliative radiation therapy is performed on the area of ​​metastases.

Chemotherapy should be discontinued when the full therapeutic effect is obtained or when treatment is ineffective.

The most acceptable modes of chemotherapeutic effects in patients with breast cancer with liver metastases are schemes. involving the use of docetaxel and pacliggaxel alone or in combination with doxorubicin.

When treating patients with breast cancer with predominant localization of metastases in soft tissues, it is advisable to give preference to the vinorelbine-5-fluorouracil regimen.

The antitumor efficacy of vinorelbine in injection form and for oral administration (capsules) is the same. However, the doses are different: 25 mg / m and 30 mg / m 2 when administered intravenously are equivalent to 60 mg / m "; and 80 mg / m"; when taken orally.

Monotherapy:

Vinorelbine - 25-30 mg / m 2 intravenously or 60-80 mg / m 2
inside once a week.

Epirubicin - 30 mg / m 2 intravenously on days 1, 8, 15.

Interval 3 weeks.

3. Calcium folinate 100 mg/m 2 from days 1 to 5.

5-fluorouracil 425 mg/m 2 intravenously as a bolus from days 1 to 5. Interval 4 weeks.

4. Mitoxantrone 10-14 mg/m 2 intravenously on the 1st day (30-
minute infusion).

Interval 3 weeks.

5. Docetaxel 100 mg/m 2 intravenously on the 1st day (1 hour
infusion).

Interval 4 weeks.

6. Paclitaxel 175 mg/m 2 (3-hour intravenous infusion).

Interval 3 weeks. Polychemotherapy1.CMF

cyclophosphamide 600 mg / m "; on the 1st and 8th days;

methotrexate 40 mg/m 2 on the 1st and 8th days;

5-fluorouracil 600 mg/m 2 on days 1 and 8.
An interval of 3 weeks (the course is repeated on the 28th day).

epirubicin 60-90 mg/m 2 on the 1st day;

cyclophosphamide 600 mg/m 2 (8-15 min infusion) on the 1st day.
Interval 3 weeks.

3. Vinorelbine + mitoxantrone

vinorelbine 25 mg/m 2 on the 1st and 8th days;

mitoxantrone 12 mg/m 2 on the 1st day.
An interval of 3 weeks (the course is repeated on the 29th day).

4. doxorubicin + docetaxel

doxorubicin 60 mg/m on day 1;

docetaxel 75 mg/m 2 on day 1, infusion 1 hour.
Interval 3-4 weeks.

5. doxorubicin + paclitaxel

doxorubicin 60 mg/m"; intravenously on the 1st day;

paclitaxel 175 mg/m 2 intravenously (infusion 3 hours) in the 1st
day.

Interval 3-4 weeks.

5-fluorouracil 500 mg/m 2 intravenously on day 1;

epirubicin 50-120 mg/m"; intravenously on the 1st day;

cyclophosphamide 500 mg/m"; intravenously on day 1.
Interval 3-4 weeks.

7. Vinorelbine + 5-fluorouracil

vinorelbine 30 mg/m intravenously on days 1 and 5;

5-fluorouracil - continuous intravenous administration
750 mg / m / day from the 1st to the 5th days.

Interval 3 weeks.

8. Vinorelbine-doxorubicin

Vinorelbine 25 mg/m 2 on the 1st and 8th days;

Doxorubicin 50 mg/m 2 on the 1st day.
Interval 3 weeks.

Treatment of patients in menopause

Treatment of patients with breast cancer in menopause begins with the appointment of tamoxifen at a dose of 20 mg daily. A month later, the reactions of the tumor and metastases to endocrine therapy are evaluated. Depending on the type of therapeutic effect, variants of the hormonal sensitivity of the tumor are determined and, in accordance with them, either sequential hormone therapy regimens, or chemohormonal treatment, or polychemotherapy are carried out. Further treatment is identical to that in patients with stage IV breast cancer with preserved ovarian function.

With the appearance of relapses of the disease after previous therapy, treatment is always individual.

Breast cancer in men

Breast cancer in men is treated in the same way as breast cancer in women with a central localization of the tumor. It should be remembered that organ-preserving operations in men are not performed. In all cases, a mastectomy is performed.

Paget's cancer.

In the absence of a tumor node in the mammary gland, only surgical treatment is performed (mastectomy according to Madden or Patey). It is acceptable to perform a wide central resection with postoperative radiation therapy to the mammary gland (if the woman wants to keep it). At

the presence of a tumor in the mammary gland, Paget's disease is treated as cancer of the appropriate stage.

Edematous-infiltrative cancer

1. Radiation therapy according to a radical program (first stage -
4 Gy 7 times for the mammary gland and regional zones, the second -
after 3 weeks, 2 Gy to a total dose of 60-70 Gy). AT
the interval between the first and second stages can be
bilateral oophorectomy was performed in women
premenopause (before the start of treatment, it is advisable for such patients
perform a trephine biopsy to study hormone receptor
tumor status).

2. With a receptor-positive tumor in menopause (or in
premenopause after oophorectomy) tamoxifen is prescribed for
20 mg daily for 5 years and 6 cycles of PCT on CMF regimens
or CAP, with a receptor-negative tumor - 6 courses of PCT
according to CMF or CAP schemes.

In the future - observation or palliative mastectomy (with the resumption of tumor growth or metastases in the lymph nodes).

OBSERVATION, TERMS AND SCOPE OF THE SURVEY

After the end of special treatment, during the first two years, patients are observed every 3 months, in the third year - every 4 months, in the 4-5th year - once every six months, then once a year.

When observed during the first 5 years, a complete blood count is required every six months, and then this study is carried out once a year.

At each visit, an examination by an oncologist, an oncogynecologist is required.

X-ray examination of the lungs during the first 3 years should be performed once every six months, then once a year.

CERVICAL CANCER (C 53)

According to the Belarusian Cancer Registry (Malignant neoplasms in Belarus. Minsk, 2003), the incidence of malignant neoplasms of the cervix in the Republic of Belarus was 14.4 per 100,000 inhabitants in 1993 and 16.1 in 2002

In 1993, 783 new cases of this pathology were detected in women and 848 in 2002.

In the structure of the incidence of the female population in 2002, cervical cancer accounted for 4.9%, occupying the eighth ranking place.

Among patients with cervical cancer, women aged 40-60 years predominate. The average age of the patients is 54.5 years. In recent decades, there has been an increase in the incidence of cervical cancer in young women. Early forms of the disease (cervical cancer stages I-II) are diagnosed in 63.8% of cases, advanced (stages III-IV) - in 33.2%. In 3.0% of cases, the stage cannot be established.

Early occurrence of metastases in regional lymph nodes is characteristic. Their frequency with tumor sizes within T1 is 10-25%, T2 - 25-45%, T3 - 30-65%. Hematogenous metastasis is most typical for mesonephroid, clear cell and poorly differentiated histological tumor types. When the ovaries are involved in the pathological process, the implantation pathway of metastasis is possible.

Histological classification of cervical cancer

(WHO, 1992)Squamous cell carcinoma:

keratinizing; non-keratinizing; warty; condylomatous; transitional cell; Lymphoepithelial-like.

Adenocarcinoma a:

mucinous (endocervical, intestinal and cricoid-cell;) endometrioid; clear cell; malignant adenoma; glandular-papillary; serous; mesonephroid; Other epithelial tumors:

adenosquamous cell carcinoma; clear cell cancer; adenoid cystic cancer; adenoid-basal cancer; carcinoid-like tumor; small cell cancer; undifferentiated cancer.

Anatomical regions

Malignant neoplasms of the cervix (C 53).

The interior (C 53.0).

The outer part (C 53.1).

Cervical injury extending beyond one and
more than the above localizations (C 53.8).

Cervix, part unspecified (C 53.9).

Classifications(FIGOandTNM,2002)

Cervical cancer prevalence is currently determined using FIGO and TNM staging. The classification is only applicable to cervical cancer. There should be histological confirmation of the diagnosis.

Since many patients are treated with radiation and do not undergo surgery, all patients with cervical cancer undergo clinical staging. When assessing the stages, a physical examination, imaging methods and a morphological study of tissue obtained from a biopsy of the cervix (including conical) are used.

To determine the T, N and M categories, the following procedures are necessary:

* In Tis, cystoscopy is not performed.

FIGO staging is based on surgical staging. This includes histological examination of the removed cone or amputated part of the cervix (TNM stages are based on clinical and/or pathological classification).

Regional lymph nodes

Regional lymph nodes are pelvic lymph nodes: paracervical, parametric, hypogastric (internal iliac, obturator), common iliac, external iliac, presacral, lateral sacral.

Involvement of other lymph nodes, such as the para-aortic nodes, is classified as distant metastasis.

	A drug	Single dose, mg / m 2	Route of administration	Introduction days
	Cyclophosphamide			daily 1st to 14th
	Methotrexate		intravenous bolus
	Fluorouracil		intravenous bolus
The courses of treatment are repeated every 4 weeks (the course is repeated on the 29th day, i.e. the interval between courses is 2 weeks) 6 courses.

For patients older than 60 years, the dose of methotrexate is 30 mg / m 2, fluorouracil - 400 mg / m 2.

Before starting treatment, catheterization of a peripheral or central vein is performed. The most rational is hardware infusion.

cyclophosphamide 500 mg/m 2 intravenously over 20-30 minutes on the 1st day;

fluorouracil 500 mg/m 2 intravenously by bolus on the 1st day.

Interval 3 weeks (6 courses).

201.10. 3.A-CMF:

201.10. 4. AT–CMF:

doxorubicin 50 mg/m 2 intravenously over 20-30 minutes on the 1st day;

paclitaxel 200 mg/m 2 intravenously on the 1st day against the background of pre-postmedication;

Interval 3 weeks (4 courses); then

CMF 4 courses (14-day option) interval 2 weeks;

201.10. 5. AC-T weekly:

doxorubicin 60 mg/m 2 intravenously over 20-30 minutes on day 1;

Interval 3 weeks (4 courses); then

paclitaxel 80 mg/m 2 intravenously on day 1;

Interval 1 week (12 courses);

201.10. 6. ddAC–ddT (G–CSF):

doxorubicin 60 mg/m 2 intravenously over 20-30 minutes on day 1;

cyclophosphamide 600 mg/m 2 intravenously on day 1;

Interval 2 weeks (4 courses); then

paclitaxel 175 mg/m 2 intravenously on day 1;

filgrastim 5 mcg/kg per day subcutaneously from days 3 to 10;

Interval 2 weeks (4 courses);

201.10. 7. CRBPDOCETRAS:

docetaxel 75 mg/m 2 IV on day 1;

carboplatin AUC6 intravenously on day 1;

trastuzumab 8 mg/kg (first injection 90-minute infusion), subsequent injections 6 mg/kg (30-minute infusion) intravenously on day 1;

Interval 3 weeks (6 courses);

201.10.8. Trastuzumab with an adjuvant target in the presence of a combination of the following signs: with Her2 / neu 3+ (or Her2 / neu 2+ and a positive Fish reaction), lesions of 4 or more lymph nodes, high tumor proliferative activity (Ki-67 expression level of more than 15% ). Trastuzumab regimens: first injection (mandatory in hospital) at a dose of 4 mg/kg, subsequent injections of 2 mg/kg weekly or first injection (mandatory in hospital) 8 mg/kg, subsequent injections of 6 mg/kg with an interval of 3 weeks. The duration of adjuvant therapy with trastuzumab is 1 year.

With the introduction of trastuzumab, it is necessary to monitor the ejection fraction of the left ventricle of the heart.

201.11. IV stage.

At this stage of the process, breast cancer is incurable. In some cases, as a result of treatment, it is possible to obtain long-term long-term survival and maintain the quality of life of patients.

In stage IV breast cancer, patients receive systemic therapy. Radiation therapy may be used for symptomatic purposes.

Patients with breast cancer with an ulcerated tumor, complicated by infection, bleeding, undergo a palliative mastectomy or amputation of the mammary gland for sanitary purposes. Treatment is complemented by chemoradiotherapy, hormonal therapy.

If surgical treatment is not planned, then at the first stage, a trephine biopsy of the tumor is performed, or a biopsy of a metastatic lymph node. The hormone-receptor, HER2/neu status of the tumor, the level of tumor proliferative activity Ki-67 are determined. In accordance with the result of the study, either sequential regimens of hormone therapy, or chemohormonal treatment, or polychemotherapy, or treatment with trastuzumab are carried out. Radiation therapy is performed as indicated.

With a positive hormone-receptor status of the tumor, and the presence of metastases in the bones and (or) in soft tissues (provided there are no metastases in the visceral organs), in menopausal patients, the first line of endocrine therapy is performed - tamoxifen 20 mg orally for a long time until progression. If signs of disease progression appear while taking tamoxifen, the latter is canceled, the 2nd line of endocrine therapy is prescribed - aromatase inhibitors, then the 3rd line - progestins).

In the absence of the effect of hormone therapy, successive lines of monochemotherapy are prescribed.

After the end of remission from sequential monochemotherapy regimens, polychemotherapy is performed.

In premenopausal patients with the above localization of metastases and with a positive hormone-receptor status of the tumor, castration is performed: surgical or pharmacological (goserelin). Then antiestrogen therapy with tamoxifen is performed, after which aromatase inhibitors are prescribed. 3rd line hormone therapy - progestins. In the absence of the effect of hormone therapy, sequential monochemotherapy regimens are prescribed. After the end of remission from sequential monochemotherapy regimens, polychemotherapy is performed.

With a negative hormone-receptor status of the tumor, systemic chemotherapy is performed. At the same time, in patients with HER2/neu overexpression/amplification, trastuzumab is prescribed with or without chemotherapy.

Chemotherapy regimens are the same as in the treatment of relapses and metastases of breast cancer after previous treatment.

With hypercalcemia and lytic bone metastases, bisphosphonates are prescribed for a long time.

Folfox chemotherapy regimen is a widely used technique for the treatment and prolongation of the remission period of malignant neoplasms of the colon.

Chemotherapy summarizes various schemes for the treatment of oncological neoplasms, differing in degree, severity and required dosage. FOLFOX, like other methods, has a toxic effect on the human body, but has a large percentage of treatment effectiveness compared to similar methods.

Chemotherapy is a course of strong drugs used during severe bacterial diseases, as well as oncology. The drug administration system is developed for each patient individually, taking into account the necessary exposure, form and stage of the disease.

The name of the chemotherapy system comes from the first letters of the drugs used during the course. Also, the order of the letters in the name determines the order in which the drugs are taken in this system.

The most significant differences among drug systems are the dosages, the substances that make up the drugs, and the nature of the effect.

Each of these forms has a general toxic effect, however, different forms of exposure make it possible to identify and destroy the agents of the disease.

The impact is determined by the properties of the causative agent of the disease and its biological qualities. The action of the weak side of the pathogen can reduce the spread of infection in the human body.

The FOLFOX system is called by the first letters of the cytostatic drugs included in the method.

Cytostatics are drugs whose main function is to slow down growth, development, and disrupt the process of cell division in the body. The most affected tumor cells reduce their activity due to the development of apoptosis (programmed cell death due to disturbed life processes).

The FOLFOX system includes the following preparations:

1. Folinsäure (folinic acid).
2. 5-Fluoruracil.
3. Oxaliplatin.

The second element of the system - 5-Fluoruracil is applied in two stages by injection and drip for two days.

This system is most often used to treat colorectal cancer (a severe form of oncology, the most common example is colon cancer and carcinomatosis).

Folfox Mode Efficiency

The effect and speed of treatment according to the Folfox method depends on the stage at which the disease was detected.

The statistics show that:

• the onset of remission of an oncological disease is detected in 10% of cases;
• the percentage of remission of the disease during the course is almost 8 times higher than the positive result in comparison with the passage of such methods as fluorouracil and calcium folinate, oxaliplatin.

This technique is used to treat patients who are stable and in general good health.

The folfox chemotherapy regimen is a system of strong drugs that have a toxic effect on the entire body.

Due to the nature of the substances used, the technique has pronounced side effects:

1. Diarrhea.
2. Nausea.
3. The appearance of stomatitis in the oral cavity.
4. Decrease in the number of neutrophilic leukocytes in the blood (neutropenia).
5. Decrease in the number of platelets in the blood (thrombocytopenia).

The main consequence is a decrease in the body's defenses, which makes a person more susceptible to infectious diseases (including stomatitis when the oral epithelium is damaged).

From the reviews of patients who used this scheme, it was noted that the manifestation of side effects in each case is individual.

Other chemotherapy methods

Chemotherapy has several different systems.

These include:

1. ABVD.
2. XELOX.
3. BEACOPP escalated.
4. Mayo.
5. Anthracyclines.

Folfox chemotherapy is far from the only one. The appointment of a particular therapy depends on the desired result and the required dosage of drugs during treatment.

AC Chemotherapy

The technique includes the use of drugs:

1. Cyclophosphamide - 1 dose in 21 days.
2. Adriamycin - 1 dose in 21 days.

The latter has an analogue "Doxorubicin", which is used quite often.

Side effects of the technique:

• severe nausea and vomiting;
• hair loss;
• decrease in the level of neutrophilic leukocytes in the blood.

Before starting the course, you must familiarize yourself with the list of contraindications. This method of therapy is used to initiate remission and treat malignant neoplasms of the breast.

Chemotherapy according to the XELOX scheme (CapeOx)

During the course of therapy, drugs are used:

1. Capecitabine.
2. Oxaliplatin.

The technique is repeated after 3 weeks.

Side effects of the technique:

• severe diarrhea;
• severe nausea, vomiting;
• decrease in the level of neutrophilic leukocytes in the blood;
• signs of irritated palms and soles of the feet.

Like folfox chemotherapy, it is prescribed for the treatment of malignant neoplasms of the esophagus and intestines.

Lymphoma is a cancer of the lymphatic system.

For the treatment of this disease, a complex of ABVD drugs is used, including:

1. Adriamycin.
2. Bleomycin.
3. Vinblastine.
4. Dacarbazine.

Injections of drugs are used on the first and 15 days.

Possible side effects of the technique:

• the appearance of a headache;
• hair loss;
• lowering blood pressure;
• weight loss (anorexia);
• decrease in the level of leukocytes in the blood (leukocytopenia).

The BEACOPP escalated technique is also used to treat this disease.

This regimen includes the following drugs:

1. Bleomycin.
2. Etoposide.
3. Adriamycin.
4. Cyclophosphamide.
5. Vincristine.
6. Procarbazine.
7. Prednisolone.

This complex increases the likelihood of a successful outcome of treatment, but the elements of therapy themselves are also toxic.

FAC Chemotherapy

The FAC technique is used to treat breast cancer in its early stages.

The scheme includes:

1. Fluorouracil on days 1 and 8 (intravenously).
2. Adriamycin for 1 day (intravenously).
3. Cyclophosphamide for 1 day.

Side effects of the technique include:

• inhibition of the function of blood formation;
• violation of the digestive tract;
• hair loss;
• violation of reproductive function, infertility;
• disruption of the liver.

This technique is a mirror image of CAF.

It is used as an addition during the main course of treatment.

The scheme includes:

1. Leucovorin from 1 to 5 days.
2. 5-fluorouracil from 1 to 5 days.

Between courses of therapy, an interval of 4 weeks was adopted, after switching to the third course - 5 weeks. Substances and their quantity may vary depending on the prescription of the attending physician.

Possible side effects of therapy:

• diarrhea;
• the appearance of signs of stomatitis;
• oppression of hematopoiesis;
• formation of dermatitis.

An additional method is used for the treatment of oncological neoplasms in various clinics due to its obvious properties.

Anthracycline chemotherapy regimens

Anthracyclines are commonly referred to as substances with antibiotic properties.

These include:

1. Doxorubicin.
2. Daunorubicin.
3. Idarubicin.
4. Epirubicin.

The main action of this series of drugs is the inhibition of the DNA isomerase enzyme and the activation of oxidation. Anthracyclines have a strong toxic effect on the circulatory system and gastrointestinal tract, and injection sites are affected by dermatonecrosis.

Both doctors and patients should be aware of all possible side effects and complications during therapy.

Chemotherapy is an effective technique often used in the treatment of cancer. This method is prescribed only taking into account possible improvements, side effects and consequences of treatment. Before starting therapy, the patient is given the opportunity to refuse the proposed method.