Hexamethylmelamine: A Review

Abstract

A review of the investigational oncolytic agent hexamethylmelamine (HMM) is presented. HMM probably acts as an antimetabolite. The value of HMM lies in its relatively mild hematologic toxicity, its ability to increase response and survival rates in combination, and in its response in patients refractory to standard chemotherapy. The greatest response is in advanced ovarian cancer: Alone (overall response, 28–42 percent) and in combination with cyclophosphamide, mediotrexate, and 5-fluorouracil (overall response, 76–79 percent). Lung cancer has shown response to HMM, with best activity exhibited in small cell carcinoma (20–28 percent). HMM alone has demonstrated activity (overall response, 39 percent) in Hodgkin's and non-Hodgkin's lymphomas, a rate equal to that of bleomycin, and without cross resistance to this agent. Its value in breast cancer is questionable. The average tolerated dose is 8 mg/kg/d. Major dose-limiting toxicities are gastrointestinal, although hematopoietic depression, peripheral neuropathies, and central nervous system disorders also occur. Pentamethylmelamine, a water soluble metabolite, is die potentially marketable form of the drug.