Hexamethylmelamine as second-line therapy in platin-resistant ovarian cancer

A total of 61 patients with recurrent or persistent clinically measurable platin-resistant epithelial ovarian carcinoma were treated with 260 mg/m2 oral hexamethylmelamine daily for 14 days, repeated at 4-week intervals. Platin resistance was defined as progression or stable disease during cis- or carboplatin treatment (used alone or in combination with other drugs), or relapse within 6 months after the end of that therapy. Fifty patients were evaluable for response and 57 for toxicity. The objective response rate was 14% (3 complete and 4 partial responses). The response rate was higher in patients with relapse within 6 months than in patients with progression or stable disease on platin-based therapy. This observation underscores the importance of defining response and time to progression after first-line chemotherapy. The median duration of response was 8 months and the median survival in responding patients was 9+ months versus 5 months for patients with progression on hexamethylmelamine. Nausea and vomiting requiring antiemetic treatment occurred in 8 (14%) patients and reversible peripheral neuropathy in 3 patients. Two patients developed agitation, insomnia, and depression during hexamethylmelamine therapy. In conclusion, the 14% objective response rate and the occurrence of complete responses with oral hexamethylmelamine treatment in a group of ovarian cancer patients with true platin resistance are noteworthy.