Hexamethylmelamine and Pentamethylmelamine: An Update

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Abstract
An updated review of the anticancer agents hexamethylmelamine (HMM) and its water-soluble analog pentamethylmelamine (PMM) is presented. Severe gastrointestinal and hematologic toxicity have limited the use of HMM drug combinations in ovarian cancer. Combinations involving HMM, cyclophosphamide, cisplatin, and doxorubicin in advanced ovarian cancer have resulted in only moderate response rates, with little to no change in median survival of previously treated patients. HMM now is being studied in previously untreated patients with advanced disease, in combination with these agents. In lung cancer, HMM continues to be a part of intensive and other regimens for the treatment of small-cell and non-small-cell carcinoma, although the value of the HMM is yet to be determined. Future trials have been recommended to determine whether HMM has a role in the treatment of endometrial and prostatic carcinomas. Five phase I studies of PMM have demonstrated severe, dose-limiting gastrointestinal and central nervous system toxicities. Thus, this agent may offer little advantage over HMM. Further phase I studies, with different PMM dosage schedules, are necessary before phase II studies can be recommended.