Fraiser L H, Kanekal S, Kehrer J P
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas, Austin.
Drugs. 1991 Nov;42(5):781-95. doi: 10.2165/00003495-199142050-00005.
Cyclophosphamide, an orally active alkylating agent, is widely used to treat a variety of malignant and nonmalignant disorders. Although it has some tumour selectivity, it also possesses a wide spectrum of toxicities. The requirement of metabolic activation before cyclophosphamide exerts either its therapeutic or toxic effects is well established, but has not led to effective counter-measures. Clinically, damage to the bladder (haemorrhagic cystitis), immunosuppression (when not desired) and alopecia are the most significant toxicities associated with cyclophosphamide. Cardiotoxicity is also a possibility when very high doses are given. Preventing these toxicities has focused on modifications of the treatment regimens and, in the case of haemorrhagic cystitis, the administration of a drug which is excreted in the urine where it inactivates the bladder-toxic species. As treatment regimens for cancer become more effective in prolonging a patient's life, and as cyclophosphamide receives increasing use for nonmalignant disorders, the potential for cyclophosphamide-induced cancers, particularly in the bladder, must be recognised. Although the toxicities associated with cyclophosphamide are serious, this agent remains a highly effective drug in many situations. Research on the pathways which play an important role in activating this drug may improve our ability to target particular diseases and decrease unwanted side effects.
环磷酰胺是一种口服活性烷化剂，广泛用于治疗各种恶性和非恶性疾病。尽管它具有一定的肿瘤选择性，但也具有广泛的毒性。环磷酰胺在发挥其治疗或毒性作用之前需要代谢活化，这一点已得到充分证实，但尚未导致有效的应对措施。临床上，膀胱损伤（出血性膀胱炎）、免疫抑制（在不需要时）和脱发是与环磷酰胺相关的最显著毒性。给予非常高剂量时也可能出现心脏毒性。预防这些毒性主要集中在调整治疗方案，对于出血性膀胱炎，则是给予一种经尿液排泄的药物，该药物可使膀胱毒性物质失活。随着癌症治疗方案在延长患者生命方面变得更加有效，以及环磷酰胺在非恶性疾病中的使用越来越多，必须认识到环磷酰胺诱发癌症的可能性，尤其是在膀胱。尽管与环磷酰胺相关的毒性很严重，但在许多情况下，这种药物仍然是一种高效药物。对激活这种药物起重要作用的途径进行研究，可能会提高我们针对特定疾病的能力，并减少不必要的副作用。
