Cerny T, Küpfer A, Zeugin T, Brunner K W
Institut für Medizinische Onkologie, Universität Bern, Switzerland.
Ann Oncol. 1990 Sep;1(5):365-8. doi: 10.1093/oxfordjournals.annonc.a057775.
The oxazaphosphorine prodrug Ifosfamide (IFO) in conjunction with the uroprotective agent Mesna is becoming a standard alkylating agent. It has an increased therapeutic index when given as a fractionated dosage over 3-5 days. Maximal fractionation is achieved by continuous infusion over several days and has been shown to be less emetic and neurotoxic than regimens with bolus infusions. We have studied in patients with advanced cancer the feasibility and bioavailability of a subcutaneously administered isotonic and neutral (pH 7) IFO solution given continuously over 10 h for up to 5 days. A portable disposable gas-driven infusor syringe was used. Our results show 90-100% bioavailability of sc administered IFO. The isotonic solution of IFO (pH 7) showed no significant local toxicity during or after sc administration. Haematotoxicity was equal for sc and iv application. No uro- or neurotoxicity has been observed in 24 sc cycles. We conclude that this novel continuous sc IFO infusion over several days is a rational, well-tolerated and economical way of delivering this drug on an outpatient basis.
恶唑磷前体药物异环磷酰胺（IFO）与尿路保护剂美司钠联合使用正成为一种标准的烷化剂。当以分次给药的方式在3 - 5天内给药时，其治疗指数会提高。通过连续输注数天可实现最大程度的分次给药，并且已证明与推注输注方案相比，其催吐和神经毒性更小。我们在晚期癌症患者中研究了皮下注射等渗中性（pH 7）的IFO溶液，连续10小时给药，持续5天的可行性和生物利用度。使用了便携式一次性气体驱动输注注射器。我们的结果显示皮下注射IFO的生物利用度为90 - 100%。IFO的等渗溶液（pH 7）在皮下给药期间或之后未显示出明显的局部毒性。皮下给药和静脉给药的血液毒性相同。在24个皮下给药周期中未观察到尿路或神经毒性。我们得出结论，这种连续数天皮下注射IFO的新方法是一种在门诊基础上给药的合理、耐受性良好且经济的方式。
