A pilot study of alternating courses of cisplatin/cyclophosphamide and carboplatin/etoposide in advanced ovarian cancer

Objectives: Platinum based chemotherapy is standard therapy for advanced epithelial ovarian cancer. Dose limiting side effects often result in dose reduction or premature cessation of therapy. Cisplatin and carboplatin have similar efficacy in ovarian cancer but different toxicity profiles. By alternating therapy, dose intensity may be achieved with a reduction in side effects. Methods: Over an 11 month period, patients with advanced or recurrent epithelial ovarian cancer were entered in an adjuvant trial of alternating cisplatin and carboplatin based chemotherapy. The cancer was optimally debulked in 7 of the 9 evaluable patients. An average of 6.1 courses of chemotherapy was prescribed to each patient. Results: Response to therapy included 3 partial and 4 complete clinical responses whereas 2 patients had progressive disease. Four of 6 eligible patients underwent second look laparotomy and one presented a complete pathological response. Fifty seven treatment cycles were evaluable for toxicity assessment. Hemoglobin toxicity was limited to grade 1 toxicity in 72% of cycles and grade 2 in 18% of cycles. Thirty nine percent of cycles were complicated by grade 3 or 4 white cell toxicity. Significant platelet toxicity (less than 50,000 x 10⁹L) was observed in only 8% of cycles. Ninety eight percent of the projected cisplatin dose and 102% of the projected carboplatin dose was able to be given. This was associated with a modest delay in giving the next course, with an average 4.4 weeks between courses per patient. The median survival of the study group was 17.3 months (range 5.9-32.2). Patients with optimal cytoreduction had a median survival of 18 months and those with a complete clinical response at the completion of therapy had a median survival of 27.1 months. Conclusions: This study demonstrated that alternating courses of cisplatin/cyclophosphamide and carboplatin/etoposide is well tolerated. It allows over 98% of the projected dose of the platinum agent to be given with acceptable response and survival rates.