Combination chemotherapy with or without hexamethylmelamine in alkylating-agent resistant ovarian carcinoma

The study was designed to determine the efficacy of a two-drug and three-drug combination chemotherapy regimen for patients with advanced epithelial ovarian carcinoma resistant to alkylating monotherapy. Patients were randomized to receive either Adriamycin (doxorubicin) and cis-diamminedichloroplatinum(II) (AP) repeated every 3 weeks, or AP plus hexamethylmelamine (HAP) repeated every 5 weeks. Forty-five patients were evaluable for response and 49 for survival. No significant differences were found between the treatment groups as to response rate, progression-free survival, and survival. A remission was achieved in 20% of the patients and stable disease in another 20%. Median progression-free survival of all patients was only 4 months (median survival, 6 months). All patients showed progressive disease within 13 months after the onset of chemotherapy. Patients responding to treatment and those with an interval of more than 2 years between the initial diagnosis and cancer recurrence, experienced prolonged survival. Two conclusions can be drawn from the results of this study; neither of the regimens is superior to the other, and the effect of both in alkylator-resistant patients with ovarian cancer are meager. In studies on salvage chemotherapy, to the contrary, these combinations induced remissions in more than 40% of the patients. This difference in response rate might be due to differences between the prognostic factors of the patient populations. Better results are to be expected when these drugs are used in initial drug programs for previously untreated patients.