Prospective sequential trials of induction weekly cisplatin followed by monthly cisplatin, doxorubicin, cyclophosphamide and paclitaxel and cisplatin in optimal (< or = 1 cm) stage III and IV ovarian cancer.

Purpose Of Investigation: This study was conduced to assess the results of paclitaxel plus cisplatin given over six months as firstline therapy in women with stage III and IV epithelial ovarian cancer with residual disease < 1 cm and compare it to our previous standard of cisplatin, adriamycin, and cyclophosphamide given over ten months in two sequential trials totaling 100 patients.

Methods: We compared induction weekly cisplatin (1 mg/kg x 4) followed by monthly cisplatin (50 mg/m2), doxorubicin (50 mg/m2) and cyclophosphamide (750 mg/m2) x 10 (n = 56) versus induction cisplatin (1 mg/kg x 4) followed by cisplatin (75 mg/m2) and paclitaxel (135 mg/m2) monthly over six months (n = 44).

Results: The two groups were similar in age, histologic subtypes, grade, performance status, and substage. The mean dose of cisplatin in the PAC patients was 617.1 (+/-92.7) mg/m2 as compared to 567.1 (+/-89.2) mg/m2 in the TP patients (p < 0.0001). Surgical response was assessed in 83.9% of the PAC and 86.4% of the TP patients. The incidence of nausea and vomiting, myelotoxicity and renal toxicity were similar in the two groups. Peripheral neuropathy occurred more frequently following TP (57% vs 16%; p = 0.001). Cardiac toxicity (grade 1) occurred in 39% of the PAC patients and in 4.5% of the TP patients (p < 0.001). The overall response rate (75% vs 88.7%), surgical response rate (67.9% vs 79.5%), complete surgical responses (37.5% vs 40.9%), estimated two-year survival (80.2% vs 79.6%), progression-free median survival (36 months vs 30.4 months) and two-year progression/recurrence rates (32.3% vs 46.9%), respectively, of PAC and TP patients were not statistically significant (p = NS).

Conclusions: Given the discussed limitations of the study, compared with PAC, TP did not improve overall and surgical response rates, two-year survival, two year disease-free survival, or median time of recurrence in patients with optimal (< 1 cm) stage III and IV ovarian cancer and resulted in higher peripheral neuropathy rates.