Protection by amifostine of cyclophosphamide-induced myelosuppression

The dose and schedule of administration of chemotherapeutic agents are often dictated by their bone marrow toxicity. Cumulative bone marrow damage may be associated with chronic exposure to chemotherapeutic agents such as alkylating agents. Amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA), a cytoprotective agent, protects bone marrow from this type of cumulative toxicity. Three well-controlled clinical trials have shown that amifostine can ameliorate cumulative bone marrow toxicity and the acute and chronic neutropenic and/or thrombocytopenic effects of cyclophosphamide. In a pivotal phase III study of cisplatin/cyclophosphamide with or without amifostine, amifostine treatment reduced course-by-course cumulative bone marrow damage when compared with the course-by-course cumulative myelosuppression experienced by those treated with cisplatin/cyclophosphamide alone. Despite this clinically significant cytoprotection, amifostine treatment did not adversely affect pathologically proven complete response, overall objective response rates, or survival duration associated with cisplatin/cyclophosphamide chemotherapy.