Efficacy and Safety of Trabectedin in Patients With Advanced or Metastatic Liposarcoma or Leiomyosarcoma After Failure of Prior Anthracyclines and Ifosfamide: Results of a Randomized Phase II Study of Two Different Schedules
Efficacy and Safety of Trabectedin in Patients With Advanced or Metastatic Liposarcoma or Leiomyosarcoma After Failure of Prior Anthracyclines and Ifosfamide: Results of a Randomized Phase II Study of Two Different Schedules
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DOI：
10.1200/jco.2008.21.0088
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发表时间：
2009-09-01
影响因子：
45.3
通讯作者：
Le Cesne, Axel
中科院分区：
文献类型：
--
作者：
Demetri, George D.;Chawla, Sant P.;Le Cesne, Axel
目的评价曲贝替丁在成人不能切除/转移性脂肪肉瘤或平滑肌肉瘤患者中的安全性和有效性，该研究是一项开放、多中心、随机的研究。患者和方法将患者随机分为两种方案(经中心静脉途径)：1.5 mg/m(2)24小时静脉滴注，每3周一次(q3周24小时)，与0.58 mg/m(2)每周3-h静脉滴注(qwk 3-h)。结果270名患者被随机分配；136名(Q3周24小时)与134名(QWK 3小时)。中位TTP为3.7月对2.3月(风险比[HR]，0.734；95%CI，0.554至0.974；P=.0302)，倾向于Q3周24小时组。中位无进展生存期分别为3.3月和2.3月(HR，0.755；95%CI，0.574至0.992；P=.0418)。中位总生存期(n=235)分别为13.9个月和11.8个月(HR，0.843；95%CI，0.653~1.090；P=.1920)。虽然中性粒细胞减少、AST/ALT升高、呕吐和疲劳在Q3周24小时内发生，但该方案耐受性良好。发热的中性粒细胞减少是罕见的(0.8%)。结论先前的研究表明，标准化疗失败后使用曲贝替丁对肉瘤患者有临床益处。这项试验记录了Q3周24小时Trabectedin方案在脂肪肉瘤和平滑肌肉瘤中的卓越疾病控制，尽管QWK 3小时方案也显示出相对于历史比较的活性。在现有的标准治疗失败后，Trabectedin现在可能被认为是控制患者晚期肉瘤的重要新选择。
PurposeTo evaluate the safety and efficacy of trabectedin in a phase II, open-label, multicenter, randomized study in adult patients with unresectable/metastatic liposarcoma or leiomyosarcoma after failure of prior conventional chemotherapy including anthracyclines and ifosfamide.Patients and MethodsPatients were randomly assigned to one of two trabectedin regimens (via central venous access): 1.5 mg/m(2) 24-hour intravenous infusion once every 3 weeks (q3 weeks 24-hour) versus 0.58 mg/m(2) 3-hour IV infusion every week for 3 weeks of a 4-week cycle (qwk 3- hour). Time to progression (TTP) was the primary efficacy end point, based on confirmed independent review of images.ResultsTwo hundred seventy patients were randomly assigned; 136 (q3 weeks 24-hour) versus 134 (qwk 3-hour). Median TTP was 3.7 months versus 2.3 months (hazard ratio [HR], 0.734; 95% CI, 0.554 to 0.974; P = .0302), favoring the q3 weeks 24-hour arm. Median progression-free survival was 3.3 months versus 2.3 months (HR, 0.755; 95% CI, 0.574 to 0.992; P = .0418). Median overall survival (n = 235 events) was 13.9 months versus 11.8 months (HR, 0.843; 95% CI, 0.653 to 1.090; P = .1920). Although somewhat more neutropenia, elevations in AST/ALT, emesis, and fatigue occurred in the q3 weeks 24-hour, this regimen was reasonably well tolerated. Febrile neutropenia was rare (0.8%). No cumulative toxicities were noted.ConclusionPrior studies showed clinical benefit with trabectedin in patients with sarcomas after failure of standard chemotherapy. This trial documents superior disease control with the q3 weeks 24-hour trabectedin regimen in liposarcomas and leiomyosarcomas, although the qwk 3- hour regimen also demonstrated activity relative to historical comparisons. Trabectedin may now be considered an important new option to control advanced sarcomas in patients after failure of available standard-of-care therapies.