van Oosterom A T, Mouridsen H T, Nielsen O S, Dombernowsky P, Krzemieniecki K, Judson I, Svancarova L, Spooner D, Hermans C, Van Glabbeke M, Verweij J
Department of Oncology, University Hospitals Leuven, Herestraat 49, B-3000 Leuven, Belgium.
Eur J Cancer. 2002 Dec;38(18):2397-406. doi: 10.1016/s0959-8049(02)00491-4.
The aim of this phase II study was to evaluate the efficacy and toxicity of two regimens of ifosfamide in metastatic soft tissue sarcoma patients given as first- and second-line chemotherapy. Two different schedules of ifosfamide were investigated in a randomised manner: Ifosfamide was given either at a dose of 5 g/m(2) over 24 h (5 g/m(2)/1 day), every 3 weeks or at a dose of 3 g/m(2) per day, administered over 4 h on three consecutive days (3 g/m(2)/3 days), every 3 weeks. Both schedules were given as first-line or second-line chemotherapy. A total of 182 patients was entered, 103 in first- and 79 in second-line, of whom 8 patients were ineligible, 5 in the first- and 3 in the second-line study. Most patients had a leiomyosarcoma, 46 of the 98 in the first-line and 34 of the 76 in the second-line. The two study arms were well balanced in both the first- and second-lines with respect to sex, age and performance status. In first-line treatment, 5 g/m(2)/1 day yielded five partial responses (PR) (Response Rate (RR) 10%), versus 12 PR (RR 25%) for the 3 g/m(2)/3 days. As second-line treatment, the 24-h infusion yielded: one CR and one PR (RR 6%) and the 3-day schedule one CR and two PR (RR 8%). Survival did not differ between the two regimens. The major World Health Organization (WHO) grade 3 and 4 toxicities encountered were: leucopenia in 19% of all courses in the first-line and 32% in the second-line with the 5 g/m(2)/1 day, while for the 3 g/m(2)/3 days schedule the rates were 57 and 63% respectively. Grade 3 or 4 infections were seen in 4% of patients treated with 5 g/m(2)/1 day first-line and 10% of patients given 3 g/m(2)/3 days, both as first- and second-lines. No such infections were seen in patients receiving 5 g/m(2)/1 day as second line treatment. In advanced soft-tissue sarcomas in the first-line, ifosfamide 3 g/m(2), given over 4 h on three consecutive days, is an active regimen with acceptable toxicity while the 5 g/m(2) over 24 hours schedule resulted in a disappointing response rate.
本II期研究的目的是评估异环磷酰胺两种给药方案作为一线和二线化疗用于转移性软组织肉瘤患者时的疗效和毒性。以随机方式研究了两种不同的异环磷酰胺给药方案：异环磷酰胺以5 g/m²的剂量在24小时内给药（5 g/m²/1天），每3周一次，或以3 g/m²/天的剂量，连续三天每天给药4小时（3 g/m²/3天），每3周一次。两种方案均作为一线或二线化疗给药。共纳入182例患者，其中103例为一线治疗，79例为二线治疗，其中8例不符合入组标准，一线治疗组5例，二线治疗组3例。大多数患者患有平滑肌肉瘤，一线治疗的98例中有46例，二线治疗的76例中有34例。两个研究组在一线和二线治疗中，在性别、年龄和体能状态方面均具有良好的平衡性。在一线治疗中，5 g/m²/1天方案产生了5例部分缓解（PR）（缓解率（RR）为10%），而3 g/m²/3天方案为12例PR（RR为25%）。作为二线治疗，24小时输注方案产生：1例完全缓解（CR）和1例PR（RR为6%），3天给药方案产生1例CR和2例PR（RR为8%）。两种方案的生存率无差异。所遇到的主要世界卫生组织（WHO）3级和4级毒性反应为：一线治疗中，5 g/m²/1天方案在所有疗程中有19%发生白细胞减少，二线治疗中有32%发生；而3 g/m²/3天方案的发生率分别为57%和63%。一线治疗中，5 g/m²/1天方案治疗的患者有4%发生3级或4级感染，3 g/m²/3天方案治疗的患者有10%发生，一线和二线治疗均如此。接受5 g/m²/1天方案作为二线治疗的患者未发生此类感染。在一线晚期软组织肉瘤中，异环磷酰胺3 g/m²连续三天每天给药4小时是一种有效的方案，毒性可接受，而24小时内给予5 g/m²的方案缓解率令人失望。
