Hexamethylmelamine in ovarian cancer after failure of cisplatin-based multiple-agent chemotherapy

A prospective study was initiated in 1979 to investigate the effect of hexamethylmelamine (HMM) as a second-line chemotherapeutic agent in the treatment of advanced adenocarcinoma of the ovary after failure of cisplatin-based multiple-agent chemotherapy. Of 20 evaluable patients, there were 5 patients (25%) who had objective responses (4 complete and 1 partial). Four additional patients have remained without evidence of disease. Six of these 9 patients are still alive, disease free. There were significant differences (P < 0.001) in both the progression-free interval and survival time for these 9 patients, 13.3 and 15.1 months, respectively, as compared to the 15 nonresponders, 0.8 and 5.8 months, respectively. There was no significant difference in survival between the 4 patients with stable disease and the 11 patients with progressive disease. Performance status less than 2 (P < 0.05) and absence of clinically measurable disease at the time of entry into the study (P < 0.05) were found to be significant variables with regard to determining outcome. Only 2 of 24 patients suffered severe enough side effects from the HMM to warrant its discontinuation. This study demonstrates that HMM at doses of 6-8 mg/kg/day for 21 out of every 28 days can induce a complete response and provide an extended disease-free interval and prolonged survival with tolerable side effects in a significant number of patients with ovarian cancer who have previously failed cisplatin-based multiple-agent chemotherapy.