Failure of hexamethylmelamine as salvage therapy in ovarian epithelial adenocarcinoma resistant to combination chemotherapy.

Favorable responses to hexamethylmelamine (HMM) have been documented in untreated as well as in alkylating agent-resistant ovarian epithelial adenocarcinoma (OvCa). Platinum-based combination therapy for OvCa has been used since 1976. Eighteen patients with OvCa were treated with HMM as salvage therapy between February 1979 and October 1981. All patients had histologically confirmed OvCa. Eleven tumors were grade III/III and seven tumors were grade II/III. Sixteen patients had received cisplatin-based combination therapy, whereas two had received doxorubicin/cyclophosphamide because of other medical conditions. HMM was used alone in 16 patients and in combination with other drugs in two patients. The initial dose of HMM was 300 mg/m2/day X 14 days when used alone and 130 mg/m2/day X 14 days when used in combination with other drugs. Six patients were treated at a reduced initial dose because of prior marrow toxicity. Adverse effects were tolerable, with 14 patients experiencing hematologic toxicity (5 mild, 5 moderate, 3 severe, 1 life threatening) and 15 patients experiencing GI toxicity (5 mild, 7 moderate, 3 severe). Only 2 patients experienced no toxicity. No objective tumor responses were observed. Four patients had progression of tumor within 4 weeks of starting therapy and 14 patients had stable disease with a mean progression-free interval of 21 weeks. Although HMM is an active drug in untreated and alkylating agent-resistant OvCa, experience suggests that HMM at the dose and schedule tested has insignificant activity in patients who have failed cisplatin-based combination therapy.