Altretamine

Altretamine is an antitumor agent which also acts as a chemosterilant for male houseflies and other insects. Altretamine is also an antineoplastic.

Altretamine.[Pubmed:1905441]

DICP. 1991 Feb;25(2):146-52.

Altretamine is a National Cancer Institute-designated group C antineoplastic agent used in the treatment of advanced ovarian cancer. Altretamine is a highly lipid-soluble drug available only for oral administration as a capsule. The drug is activated through metabolic oxidation to intermediate methylol derivatives and formaldehyde. It is unclear which metabolite is the major species responsible for cytotoxicity or the primary mechanism of cytotoxicity. As a single agent in the treatment of ovarian cancer, Altretamine demonstrates a response rate similar to other active agents in this disease (21-39 percent). The major utility of Altretamine is in combination with other agents such as cyclophosphamide, doxorubicin, fluorouracil, melphalan, and cisplatin. However, few randomized trials have evaluated the contribution of Altretamine in these multiagent combinations. Dose-limiting toxicities include gastrointestinal (nausea, vomiting, anorexia), hematologic, and neurotoxic (peripheral neurotoxicity). The therapeutic role of Altretamine is limited because of a toxicity profile similar to that of cisplatin, one of the more active agents in ovarian cancer. Its use should be reserved for patients who are not candidates for more standard platinum-based regimens.

Altretamine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in cancer chemotherapy.[Pubmed:7641606]

Drugs. 1995 Jun;49(6):932-53.

Altretamine (hexamethylmelamine) is a cytotoxic antineoplastic agent which appears to require metabolic activation. Metabolic intermediates may act as alkylating agents; however, Altretamine is not directly cross-resistant with classical alkylating agents. Objective response rates to orally administered Altretamine as salvage therapy in patients with advanced ovarian cancer were 0 to 33%, with disease stabilisation in a further 8 to 78% of patients. Response rates appear to be higher in patients who have responded to previous alkylating agent or cisplatin-based therapy. There is some evidence that addition of Altretamine to platinum-based combination regimens used for induction therapy of advanced ovarian cancer may improve long term survival, particularly in patients with limited residual disease. Although Altretamine displays some activity in small cell lung cancer, it is unlikely to have any clinical role in the management of non-ovarian cancer. Altretamine appears to be relatively well tolerated, with gastrointestinal, neurological and haematological toxicities being the main dose-limiting adverse effects. However, assessment of accurate incidence rates for these effects is complicated by the use of Altretamine with cisplatin. On the basis of the emerging body of clinical evidence, Altretamine appears to have a limited role in the treatment of persistent or recurrent advanced ovarian cancer, primarily in patients who are potentially platinum sensitive yet intolerant of platinum analogues. Additionally, Altretamine may be added to platinum-based regimens for induction therapy of advanced ovarian cancer. At the doses currently recommended, Altretamine offers a reasonably well tolerated regimen that can be administered orally and is suitable for use on an outpatient basis.