Manegold C, Bischoff H, Fischer J R, Löchner S, Peukert M, Schmähl A, Drings P
Thorax Hospital Heidelberg-Rohrbach, Germany.
Ann Oncol. 1992 Nov;3(9):723-6. doi: 10.1093/oxfordjournals.annonc.a058327.
The purpose of this study was to evaluate the toxicity and response efficacy of fixed-dose oral ifosfamide (OI)-mesna (M) in advanced, non-small-cell lung cancer (NSCLC). OI was given in four different fractionated-dose treatment schedules with a total dose per cycle of either 3.0 g/m2, 6.0 g/m2, 7.5 g/m2 or 10 g/m2 (equivalent to a daily dose of either 750 mg, 1000 mg or 1250 mg.) M was given p.o. by drinking ampules. In the 64 patients (pts) included, a total of 305 treatment cycles were administered with no evidence of severe neurotoxicity. Twenty-two pts (37%) developed mild to moderate CNS toxicity. Neither myelosuppression, alopecia, gastrointestinal toxicity nor urotoxicity were clinical problems. On schedule 2 (6 g/m2), 3 of 14 evaluable pts (21%) had partial remissions (PR), and on schedule 3 (7.5 g/m2) 4 pts (25%) showed PRs. The median duration of response was 9 months (mts) for pts on schedule 2, and 8 mts for pts on schedule 3. We conclude that OIM can easily be tolerated in the same dose usually given intravenously (7.5 g/m2/mts), when patients at high risk for developing CNS toxicity have been previously excluded from therapy. In order to reduce CNS toxicity, it is suggested that the total dose per cycle should not exceed 7.5 g/m2 (1000 mg daily) within a fractionated-dose, 14-day treatment schedule. We further conclude that the tumor response efficacy of OIM in NSCLC is comparable to the one achieved by intravenously-administered IM, whereby the total monthly OI dose should not be less than 6.0 g/m2 (750 mg daily).
本研究的目的是评估固定剂量口服异环磷酰胺（OI）-美司钠（M）治疗晚期非小细胞肺癌（NSCLC）的毒性和反应疗效。OI采用四种不同的分次剂量治疗方案，每个周期的总剂量分别为3.0 g/m²、6.0 g/m²、7.5 g/m²或10 g/m²（相当于每日剂量750 mg、1000 mg或1250 mg）。M通过饮用安瓿口服给药。在纳入的64例患者中，共进行了305个治疗周期，未发现严重神经毒性的证据。22例患者（37%）出现轻度至中度中枢神经系统毒性。骨髓抑制、脱发、胃肠道毒性和尿路毒性均未成为临床问题。在方案2（6 g/m²）中，14例可评估患者中有3例（21%）出现部分缓解（PR），在方案3（7.5 g/m²）中，4例患者（25%）出现PR。方案2患者的中位缓解持续时间为9个月，方案3患者为8个月。我们得出结论，当先前已将发生中枢神经系统毒性高风险的患者排除在治疗之外时，OI-M可以很容易地耐受通常静脉给予的相同剂量（7.5 g/m²/月）。为了降低中枢神经系统毒性，建议在14天分次剂量治疗方案中，每个周期的总剂量不应超过7.5 g/m²（每日1000 mg）。我们进一步得出结论，OI-M在NSCLC中的肿瘤反应疗效与静脉注射IM相当，每月OI总剂量不应低于6.0 g/m²（每日750 mg）。
