A randomised phase III study comparing high-dose chemotherapy to conventionally dosed chemotherapy for stage III ovarian cancer: the Finnish Ovarian Cancer (FINOVA) study.

Women with stage III ovarian cancer and with < or = 2 cm residual tumour were randomly assigned to receive either conventionally dosed chemotherapy (group A) or HDCT (group B). Patients allocated to group A received 6 cycles of paclitaxel (T) 135 mg/m2 and cisplatin (P) 75 mg/m2 every 3 weeks, and those allocated to HDCT received 3 TP cycles followed by peripheral blood stem cell mobilisation with cyclophosphamide (C) 3000 mg/m2 and T 175 mg/m2, and subsequently HDCT with carboplatin 1500 mg/m2, C 120 mg/kg, and mitoxantrone 75 mg/m2. The trial was closed early after 42 patients were entered due to slow accrual. The median follow-up time of patients who were alive was 81 months. The median progression-free survival time was 15.9 and 16.6 months (hazard ratio, HR 0.83; 95% CI 0.41-1.69, P = 0.61) and the median overall survival time was 43.7 and 64.3 months (HR, 0.74; 95% CI 0.34-1.61, P = 0.44) in groups A and B, respectively. Although one patient died of HDCT-related toxicity, the regimen was otherwise relatively well tolerated. We conclude that the HDCT regimen used was feasible, but did not result in significantly improved survival in this prematurely closed trial. A clinically important survival benefit cannot be excluded due to the small sample size.

Sequential gemcitabine-carboplatin followed by paclitaxel-carboplatin in the first-line treatment of advanced ovarian cancer: A phase II study.

OBJECTIVE: To determine the feasibility and efficacy of sequential gemcitabine-carboplatin followed by paclitaxel-carboplatin in the first-line treatment of advanced epithelial ovarian cancer, with the response rate as the primary endpoint. METHODS: After primary laparotomy, 56 patients with FIGO Stages III-IV disease were given 4 cycles of gemcitabine 1000 mg/m2 d1,8 and carboplatin AUC5 (44 patients) or AUC6 (12 patients) d1 q3wk followed by 4 cycles of paclitaxel 175 mg/m2 d1 and carboplatin AUC5/6 q3wk. Of the tumors, 43 were serous, 6 clear cell, 4 endometrioid, and 3 anaplastic type. Thirty-seven (66.1%) of the patients were suboptimally debulked. RESULTS: Forty-seven patients were evaluable for response by CA-125 criteria, and 46 (98%) responded. Thirty patients (after gemcitabine-carboplatin) and 24 (after paclitaxel-carboplatin) were evaluable for response by CT (RECIST criteria), respectively. After the four gemcitabine-carboplatin cycles, the objective response rate was 83% (6 CR, 19 PR). Following completion of the whole sequential regimen, 7 patients showed a CR and 15 a PR, respectively, giving a response rate of 92%. The median progression-free survival was 12.8 months after a median follow-up of 19 months (range 7-35 months). The median overall survival has not been reached yet. The main toxicity was neutropenia as 139/221 (62.9%) of the gemcitabine-carboplatin cycles and 92/181 (50.8%) of the paclitaxel-carboplatin cycles, respectively, were associated with Grades 3-4 neutropenia. Neutropenia was reported as a serious adverse event in 5.7% of the cycles, and G-CSF support was needed in 18.4% of the cycles. Only the gemcitabine-carboplatin cycles were associated with a marked thrombocytopenia (32.1% Grades 3-4). Of the other side effects, marked allergy occurred in 14/52 (27%) exposed to paclitaxel. A total of 14 patients discontinued the treatment prematurely: 3 due to lack of efficacy, 1 due to protocol violation, and 10 due to toxicity (4 allergic reactions to paclitaxel, 3 complicated neutropenias, 1 fever, and 2 unspecified toxicities). The mean relative dose intensities were: gemcitabine 84.0%, paclitaxel 85.4%, and carboplatin 96.5%. Of the gemcitabine-carboplatin cycles and paclitaxel-carboplatin cycles, 32% and 38% were delayed, respectively. Gemcitabine d8 dose had to be omitted in 8% of the cycles. CONCLUSION: The sequential regimen of gemcitabine-carboplatin followed by paclitaxel-carboplatin is feasible in chemotherapy-naive ovarian cancer. Although its use is associated with a marked neutropenia, the neutropenia is manageable.