indication

For use as a single agent in the palliative treatment of patients with persistent or recurrent ovarian cancer following first-line therapy with a cisplatin and/or alkylating agent-based combination.

pharmacology

Altretamine is a novel antineoplastic agent. The precise mechanism by which altretamine exerts its cytotoxic effect is unknown, although a number of theoretical possibilities have been studied. Structurally, altretamine resembles the alkylating agent triethylenemelamine, yet in vitro tests for alkylating activity of altretamine and its metabolitics have been negative. Altretamine has been demonstrated to be efficacious for certain ovarian tumors resistant to classical alkylating agents. Metabolism of altretamine is a requirement of cytotoxicity. Synthetic monohydroxymethylmelamines, and products of altretamine metabolism, in vitro and in vivo, can form covalent adducts with tissue macromolecules including DNA, but the relevance of these reactions to antitumor activity is unknown.

mechanism of action

The precise mechanism by which altretamine exerts its cytotoxic effect is unknown although it is classified as an alkylating anti-neoplastic agent. Through this mechanism, the drug is metabolized into alkylating agents by N-demethylation. These alkylating species consequently damage tumor cells.

half life

4.7-10.2 hours

route of elimination

Human urinary metabolites were Ndemethylated homologues of altretamine with <1% unmetabolized altretamine excreted at 24 hours.

drug interactions

Amitriptyline: Risk of severe hypotension

Amoxapine: Risk of severe hypotension

Clomipramine: Risk of severe hypotension

Desipramine: Risk of severe hypotension

Doxepin: Risk of severe hypotension

Imipramine: Risk of severe hypotension

Isocarboxazid: Risk of severe hypotension

Nortriptyline: Risk of hypotension

Phenelzine: Risk of severe hypotension

Rasagiline: Risk of severe hypotension

Trastuzumab: Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events.