Jassem Jacek, Ramlau Rodryg, Santoro Armando, Schuette Wolfgang, Chemaissani Assad, Hong Shengyan, Blatter Johannes, Adachi Susumu, Hanauske Axel, Manegold Christian
Radiotherapy and Oncology, Medical University of Gdansk, Debinki 7 St, Gdansk, Poland.
J Clin Oncol. 2008 Apr 1;26(10):1698-704. doi: 10.1200/JCO.2006.09.9887.
This multicenter, phase III study compared overall survival (OS) of second-line pemetrexed plus best supportive care (BSC) versus BSC alone in patients with advanced malignant pleural mesothelioma (MPM). Secondary end points included response rate, progression-free survival (PFS), time to tumor progression (TTP), time to treatment failure (TTF), and toxicity.
Patients with relapsed MPM after first-line chemotherapy were randomly assigned to receive pemetrexed 500 mg/m(2) plus BSC (P+BSC) every 21 days or BSC alone.
The study enrolled 243 patients (123 on P+BSC arm and 120 on BSC arm). Median OS time was not significantly different between the arms (8.4 months for P+BSC and 9.7 months for BSC; P = .74). Cox regression modeling suggested a trending survival benefit for patients who responded to first-line therapy. Time-to-event measures significantly favored P+BSC (median PFS, TTP, and TTF). Partial response was achieved in 18.7% and 1.7% of patients in P+BSC and BSC arms, respectively (P < .0001), and a disease control rate (partial response plus stable disease) was achieved in 59.3% and 19.2% of patients in P+BSC and BSC arms, respectively (P < .0001). Use of postdiscontinuation chemotherapy was significantly greater among BSC patients compared with P+BSC patients (51.7% v 28.5%, respectively; P = .0002), with more BSC patients receiving pemetrexed (18.3% v 3.3%, respectively; P = .0001). Postdiscontinuation therapy was initiated earlier for BSC than P+BSC patients (median time to initiation, 4.3 v 15.7 months, respectively; log-rank P < .0001). Chemotherapy was well tolerated, with expected modest (4% to 7%) grade 3 and 4 hematologic toxicities.
Second-line pemetrexed elicited significant tumor response and delayed disease progression compared with BSC alone in patients with advanced MPM. Improvement in OS was not seen in this study, possibly because of the significant imbalance in postdiscontinuation chemotherapy between the arms.
本多中心III期研究比较了二线培美曲塞联合最佳支持治疗（BSC）与单纯BSC对晚期恶性胸膜间皮瘤（MPM）患者总生存期（OS）的影响。次要终点包括缓解率、无进展生存期（PFS）、肿瘤进展时间（TTP）、治疗失败时间（TTF）和毒性。
一线化疗后复发的MPM患者被随机分配接受每21天一次的培美曲塞500mg/m²联合BSC（P+BSC）或单纯BSC治疗。
该研究纳入了243例患者（P+BSC组123例，BSC组120例）。两组的中位OS时间无显著差异（P+BSC组为8.4个月，BSC组为9.7个月；P = 0.74）。Cox回归模型表明，对一线治疗有反应的患者有生存获益的趋势。事件发生时间指标显著有利于P+BSC组（中位PFS、TTP和TTF）。P+BSC组和BSC组分别有18.7%和1.7%的患者获得部分缓解（P < 0.0001），P+BSC组和BSC组分别有59.3%和19.2%的患者获得疾病控制率（部分缓解加病情稳定）（P < 0.0001）。与P+BSC组患者相比，BSC组患者中停止治疗后化疗的使用率显著更高（分别为51.7%和28.5%；P = 0.0002），接受培美曲塞治疗的BSC组患者更多（分别为18.3%和3.3%；P = 0.0001）。BSC组患者停止治疗后开始治疗的时间比P+BSC组患者更早（中位开始时间分别为4.3个月和15.7个月；对数秩检验P < 0.0001）。化疗耐受性良好，有预期的适度（4%至7%）3级和4级血液学毒性。
在晚期MPM患者中，与单纯BSC相比，二线培美曲塞可引起显著的肿瘤反应并延迟疾病进展。本研究未观察到OS的改善，可能是因为两组在停止治疗后化疗方面存在显著失衡。
