Cyclophosphamide, epirubicin and cisplatin (CEP) versus epirubicin plus cisplatin (EP) in stage Ic-IV ovarian cancer: a randomized phase III trial of the Gynecologic Oncology Group of the Comprehensive Cancer Center Limburg.

Cisplatin is the most important drug in the treatment of advanced ovarian cancer. The role of anthracyclines is controversial. We compared a combination of epirubicin plus cisplatin (EP) with a regimen of cyclophosphamide, epirubicin and cisplatin (CEP). Patients with stage Ic-IV ovarian cancer were randomized to receive either epirubicin 100 mg/m2 plus cisplatin 75 mg/m2 q 4 weeks or cyclophosphamide 500 mg/m2 plus epirubicin 75 mg/m2 plus cisplatin 50 mg/m2 q 4 weeks, which we considered the reference treatment based on our previous experience. Patients were initially debulked, followed by six cycles of chemotherapy, or in case primary debulking was insufficient or considered inappropriate, secondary debulking was attempted in selected cases after sufficient chemotherapy-induced regression. Optimal debulking was defined as residual lesions < or = 2 cm. A total of 210 patients (191 eligible) were randomized. Results did not show significant differences in all major endpoints (pathologically documented complete response and survival). The median survival for all patients was 34 months, for patients with stage III 26 months, for patients with stage IV 20 months and it has not been reached for patients with stage Ic-II. As no significant differences between an equitoxic regimen of EP and CEP were detected, it might be more useful to look again at the anthracyclines as part of combination chemotherapy instead of the alkylating agents.

Efficacy of carboplatin plus primary prophylactic filgrastim (granulocyte colony stimulating factor) in relapsed ovarian cancer: a study of the Gynecologic Oncology Group of the Comprehensive Cancer Center Limburg.

A total of 34 patients with advanced ovarian cancer, who relapsed 1-72 months after at least one first-line cisplatin-based chemotherapy protocol, were treated with carboplatin, 350 mg/m2 q 4 weeks, with the adjunct of primary prophylactic granulocyte colony stimulating factor (G-CSF; filgrastim), 300 or 480 microg daily, days 5-9. Over 90% of the anticipated dose of carboplatin could be administered. Partial response, defined as a decline in CA-125 of 50% or more on two consecutive samples, occurred in 42%, while 15% of patients achieved a complete response (no clinical signs of disease with normalization of CA-125). Survival from start of carboplatin treatment was 23 months. Myelosuppression was the most important toxicity with 35% of patients experiencing grade 4 thrombocytopenia of short duration. Grade 4 leucopenia occurred in only one patient. It is concluded that single-agent carboplatin, with the adjunct of prophylactic G-CSF, can be administered with adequate dose intensity, and is an effective and acceptable palliative treatment for patients with relapse after first-line cisplatin-based chemotherapy.

Phase II study of sequential high-dose methotrexate (MTX) and 5-fluorouracil (F) alternated with epirubicin (E) and cisplatin (P) [FEMTX-P] in advanced gastric cancer.

BACKGROUND: FAMTX (5-fluorouracil, adriamycin, methotrexate) is one of the most effective drug combinations in gastric cancer. Therefore, modifications of FAMTX appear of interest and the FEMTX-P regiment was conceived. PATIENTS AND METHODS: Fifty patients with unresectable locally advanced and/or metastatic gastric carcinoma were treated with methotrexate 1500 mg/m2 i.v. and 5-fluorouracil 1500 mg/m2 i.v. on day 1; leucovorin rescue 15 mg/m2 orally every 6 hours for 8 doses on days 2 and 3; epirubicin 60 mg/m2 i.v. and cisplatin 50 mg/m2 i.v. on day 15, q 4 weeks. RESULTS: Of forty-seven patients evaluable for response, five (11%) achieved complete responses and seventeen (36%) partial responses (total response rate 47%). The median duration of response was 8+ months (range: 5-25+ months). Four of 14 patients with locally advanced disease were successfully downstaged and subsequently resected. The median duration of survival of all patients was 10 months (range: 1-25+ months). Leukopenia grade 4 occurred in 18% of patients and thrombocytopenia grade 4 and mucositis grade 4 in 4% and 2%, respectively. Treatment postponement for hematologic toxicity was necessary in 54% of patients. CONCLUSIONS: The FEMTX-P regimen is an active regimen in advanced gastric carcinoma, with acceptable toxicity.

[Combination of 5-FU, high dose methotrexate, epirubicin and cisplatin (FEMTX-P protocol) in non surgical or locally recurrent metastatic gastric cancers]. / Association de 5-FU, méthotrexate à haute dose, épirubicine et cisplatine (FEMTX-P) dans les cancers gastriques métastatiques, inopérables ou en récidive locale.

In this phase II study, fifty patients with unresectable locally advanced and/or metastatic gastric carcinoma were treated with methotrexate 1.5 g/m2 iv and 5-fluorouracil 1.5 g/m2 iv on day 1; leucovorin rescue 15 mg/m2 orally every 6 h for 8 doses on day 2 and 3; epirubicin 60 mg/m2 iv and cisplatin 50 mg/m2 iv on day 15, q 4 weeks. The median age of the patients was 59 years and their median performance status 1. In forty-eight patients evaluable for response, five (10.4%) of the patients achieved a complete response and seventeen (35.6%) obtained a partial response (total response rate 46%; 95% confidence interval: 32%-60%). The median duration of response was 8+ months (range: 5-25 months). The median duration of survival of all patients was 10 months (range: 1-25+ months). Toxicities > grade 2 included vomiting grade 3 (31%), leucopenia grade 4 (18%) and thrombocytopenia grade 4 (4%). Treatment postponement or dose reduction for hematologic toxicity was necessary in 54% of patients. Median survival was 10 months. In conclusion, the FEMTX-P regimen is an active treatment in advanced gastric carcinoma with acceptable toxicity.