Alberts D S
Department of Medicine and Arizona Cancer Center, College of Medicine, University of Arizona, Tucson, USA.
Semin Oncol. 1999 Apr;26(2 Suppl 7):37-40.
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.
化疗药物的给药剂量和方案通常取决于其骨髓毒性。累积性骨髓损伤可能与长期接触化疗药物（如烷化剂）有关。氨磷汀（Ethyol；Alza制药公司，美国加利福尼亚州帕洛阿尔托/美国生物科学公司，宾夕法尼亚州韦斯特康舍霍肯）是一种细胞保护剂，可保护骨髓免受此类累积毒性的影响。三项严格对照的临床试验表明，氨磷汀可改善累积性骨髓毒性以及环磷酰胺的急慢性中性粒细胞减少和/或血小板减少效应。在一项关于顺铂/环磷酰胺联合或不联合氨磷汀的关键III期研究中，与单独接受顺铂/环磷酰胺治疗的患者逐疗程累积骨髓抑制相比，氨磷汀治疗减少了逐疗程累积骨髓损伤。尽管有这种临床上显著的细胞保护作用，但氨磷汀治疗并未对经病理证实的完全缓解、总体客观缓解率或与顺铂/环磷酰胺化疗相关的生存期产生不利影响。
