C. C. Cheng

Chapter 14. Antineoplastic Agents

Publisher Summary This chapter presents an overview of antineoplastic agents. Isophosphamide, an analog of cyclophosphamide, inhibits Lewis lung carcinoma, Ehrlich ascites sarcoma, and Yoshida sarcoma. Isophosphamide generates the cytotoxic aldehyde acrolein in vitro and the latter is proposed as a component of a universal cell-growth regulatory system. Clinically, it is active in oat cell tumors of the lung, ovarian cancer, breast cancer, and lymphomas. Toxicities of both compounds are similar; they cause cardiovascular alterations in rhesus monkeys with isophosphamide being twice as potent. The hypotension and bradycardia observed after administration of these compounds may be due to a direct nonspecific cardiac depression in conjunction with possible histamine release. Bis(4-methanesulfonoxybutyl) ether and many related δ-oxygen substituted butyl ethers are effective inhibitors of the Walker rat carcinoma. Phenesterin, an alkylating cholesterol ester, is at least as effective as cyclophosphamide and about three times that of chlorambucil. The drug is more effective when given orally rather than sc or ip administration. Mode of decomposition of DIC [5-(3,3-Dimeth∼l-1-triazeno)imidazole-4-carboxamide] was studied in Bacillus subtilis and in mammalian cell cultures. In the presence of light, DIC decomposed into dimethylamine and 5-diazoimidazole-4-carboxamide, the latter enters the cells and interacts with nucleic acids in an obscure manner.