Antineoplastic Drugs in 1990: A Review (Part I)

The drugs used to treat cancer today are a confusing array of compounds with differing origins, mechanisms of action, antitumour spectra, and toxicities. There are 5 chemically distinct types of alkylating agents; the prototypical agent is chlormethine (mustine) and the most recent addition is ifosfamide. Generally these drugs all work in the same fashion and their activity is cell cycle proliferation-dependent but phase-nonspecific. The antimetabolites consist of methotrexate, the pyrimidine and purine analogues, and pentostatin, an adenosine deaminase inhibitor and relative newcomer to the class. The individual mechanisms of action of these agents differ but cytotoxicity is generally cell cycle phase-specific. Naturally occurring antineoplastic agents include the vinca alkaloids, the antitumour antibiotics, 1-asparaginase, the epipodophyllotoxins, and homoharringtonine; it is the most diverse collection of compounds. For these drugs as well as the antimetabolites, the therapeutic and toxic effects often depend heavily on duration of exposure to the drug, an effect known as schedule dependency. Finally, the agents that do not fit one of the above categories are cisplatin (cis-platinum II) and its analogue carboplatin (which is being actively investigated), hydroxycarbamide (hydroxyurea), procarbazine, hexamethylmelamine, amsacrine, and mitoxantrone (mitozantrone). In the future we can expect not only the emergence of new antineoplastic drugs, but also further refinements in the use of existing drugs. We are beginning to understand the various types of resistance manifested by tumour cells. Our ability to use these potent and highly toxic agents safely should continue to improve.