Pratt C B, Meyer W H, Douglass E C, Bowman L, Wilimas J, Ochs J, Marina N, Avery L, Thompson E I
Department of Hematology/Oncology, St. Jude Children's Research Hospital, Memphis, TN 38101-0318.
Cancer. 1993 Jun 1;71(11):3661-5. doi: 10.1002/1097-0142(19930601)71:11<3661::aid-cncr2820711131>3.0.co;2-w.
The authors conducted a Phase I dose escalation trial of ifosfamide given daily for 3 consecutive days to 29 children with malignant solid tumors. Twenty-eight of these children had received prior chemotherapy.
Patients were assigned to dosage cohorts separately on the basis of prior exposure to the platinum alkylating agents cisplatin or carboplatin (n = 20) or the absence of such exposure (n = 9). At least three patients in each category were treated at a starting dosage of 2133 mg/m2/d for 3 days. This dosage represented 80% of the total dose delivered in the prior study of ifosfamide given daily over 5 days with dosage escalation of 20% in subsequent cohorts.
Myelosuppression was dose-limiting at the second dosage level (2560 mg/m2/d) for patients previously treated with platinum and at the third dosage level (3072 mg/m2/d) for those not previously treated with platinum. Dose-limiting neurotoxicity was seen at 2560 mg/m2/d for the former group, but was not encountered in the latter group.
Delivery of ifosfamide daily for 3 days is feasible and safe at recommended dosages of 2133 mg/m2/d for children with prior exposure to platinum and 3000 mg/m2/d for those without prior exposure.
作者对29例患有恶性实体瘤的儿童进行了一项异环磷酰胺的I期剂量递增试验，异环磷酰胺连续3天每日给药。这些儿童中有28例曾接受过先前的化疗。
根据先前是否接触过铂类烷化剂顺铂或卡铂（n = 20）或未接触过此类药物（n = 9），将患者分别分配到不同的剂量组。每组至少有3名患者以2133 mg/m²/d的起始剂量治疗3天。该剂量相当于先前研究中5天每日给予异环磷酰胺的总剂量的80%，后续组剂量递增20%。
对于先前接受过铂类治疗的患者，骨髓抑制在第二个剂量水平（2560 mg/m²/d）时成为剂量限制性毒性；对于未接受过铂类治疗的患者，骨髓抑制在第三个剂量水平（3072 mg/m²/d）时成为剂量限制性毒性。对于前一组患者，在2560 mg/m²/d时出现剂量限制性神经毒性，但后一组未出现。
对于先前接触过铂类的儿童，以2133 mg/m²/d的推荐剂量连续3天每日给予异环磷酰胺是可行且安全的；对于未接触过铂类的儿童，推荐剂量为3000 mg/m²/d。
