Trabectedin Plus Pegylated Liposomal Doxorubicin in Recurrent Ovarian Cancer
Trabectedin Plus Pegylated Liposomal Doxorubicin in Recurrent Ovarian Cancer
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DOI：
10.1200/jco.2009.25.4037
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发表时间：
2010-07-01
影响因子：
45.3
通讯作者：
Poveda, Andres M.
中科院分区：
文献类型：
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作者：
Monk, Bradley J.;Herzog, Thomas J.;Poveda, Andres M.
目的比较曲贝替丁联合聚乙二醇化脂质体阿霉素(PLD)与单用PLD治疗复发性卵巢癌的疗效和安全性。患者年龄18岁，按疗效状态(0~1v2)和铂敏感性分级，随机分为两组，先静脉滴注PLD 30 mg/m(2)，然后每3周静滴1.1 mg/m(2)或每4周静滴PLD 50 mg/m(2)。结果672例患者随机分为Trabectedin/PLD组(337例)和PLD组(335例)。Trabectedin/PLD组的中位PFS为7.3个月，PLD组为5.8个月(风险比，0.79；95%CI，0.65~0.96；P=.0190)。对于铂敏感患者，中位PFS分别为9.2个月和7.5个月(风险比，0.73；95%CI，0.56至0.95；P=.0170)。Trabectedin/PLD组总有效率(ORR)为27.6%，PLD组为18.8%(P=0.0080)，铂类药物敏感组ORR为35.3%v22.6%(P=0.0042)。耐铂患者的ORR、PFS和总存活率无统计学差异。中性粒细胞减少症在Trabectedin/PLD中更为常见。联合用药后，3到4级转氨酶升高也更常见，但是暂时的和非累积的。结论在复发性卵巢癌的二线治疗中，与PLD联合应用时，Trabectedin可改善PFS和ORR，且耐受性可接受。
Purpose The objective of this study was to compare the efficacy and safety of trabectedin plus pegylated liposomal doxorubicin (PLD) with that of PLD alone in women with recurrent ovarian cancer after failure of first-line, platinum-based chemotherapy.Patients and Methods Women >= 18 years, stratified by performance status (0 to 1 v 2) and platinum sensitivity, were randomly assigned to receive an intravenous infusion of PLD 30 mg/m(2) followed by a 3-hour infusion of trabectedin 1.1 mg/m(2) every 3 weeks or PLD 50 mg/m(2) every 4 weeks. The primary end point was progression-free survival (PFS) by independent radiology assessment.Results Patients (N = 672) were randomly assigned to trabectedin/PLD (n = 337) or PLD (n = 335). Median PFS was 7.3 months with trabectedin/PLD v 5.8 months with PLD (hazard ratio, 0.79; 95% CI, 0.65 to 0.96; P = .0190). For platinum-sensitive patients, median PFS was 9.2 months v 7.5 months, respectively (hazard ratio, 0.73; 95% CI, 0.56 to 0.95; P = .0170). Overall response rate (ORR) was 27.6% for trabectedin/PLD v 18.8% for PLD (P = .0080); for platinum-sensitive patients, it was 35.3% v 22.6% (P = .0042), respectively. ORR, PFS, and overall survival among platinum-resistant patients were not statistically different. Neutropenia was more common with trabectedin/PLD. Grade 3 to 4 transaminase elevations were also more common with the combination but were transient and noncumulative. Hand-foot syndrome and mucositis were less frequent with trabectedin/PLD than with PLD alone.Conclusion When combined with PLD, trabectedin improves PFS and ORR over PLD alone with acceptable tolerance in the second-line treatment of recurrent ovarian cancer.