Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: An intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada
Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: An intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada
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DOI：
10.1200/jco.20005.14.589
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发表时间：
2005-10-01
影响因子：
45.3
通讯作者：
Giaccone, G
中科院分区：
文献类型：
--
作者：
van Meerbeeck, JP;Gaafar, R;Giaccone, G
目的我们进行了一项III期临床试验，以确定在恶性胸膜间皮瘤（MPM）患者中，与单独使用顺铂相比，雷替曲塞（一种胸苷合成酶抑制剂）和顺铂的一线治疗是否会导致上级结局。肝功能正常的受试者被随机分配接受顺铂80 mg/m2静脉给药，第1天单独给药（A组）或联合雷替曲塞3 mg/m2（B组）。在具有可测量疾病的患者中，使用实体瘤疗效评价标准监测疗效。健康相关的生活质量（HRQOL）采用欧洲癌症研究和治疗组织QLQ-C30和肺部模块（QLQ-LC 13）进行测量。结果250例患者随机分组：80%男性;中位年龄58岁; WHO PS为0，1，2的病例分别为25，62和13%。没有中毒死亡。观察到的主要3级或4级毒性反应为中性粒细胞减少和呕吐，联合用药组的报告率为2倍，在213例可测量疾病的患者中，缓解率为13.6%（A组）和23.6%（B组; P = 0.056）。在任何量表上均未观察到HRQOL差异。A组和B组的中位总生存期和1年生存期分别为8.8个月（95%CI，7.8 ~ 10.8）和11.4个月（95%CI，10.1 ~ 15），分别为40%和46%（P = 0.048）。这项研究证实，顺铂和叶酸拮抗剂的组合是上级顺铂单独与MPM患者，没有有害的影响HRQOL。
Purpose We conducted a phase III trial to determine whether first-line treatment with raltitrexed, a thymidine synthase inhibitor, and cisplatin results in superior outcome compared with cisplatin alone in patients with malignant pleural mesothelioma (MPM).Patients and Methods Eligible patients with histologically proven advanced MPM, not pretreated with chemotherapy, WHO performance status (PS) 0 to 2, and adequate hematological, renal, and hepatic function were randomly assigned to receive cisplatin 80 mg/m(2) IV on day 1, alone (arm A) or combined with raltitrexed 3 mg/m(2) (arm B). In patients with measurable disease, response was monitored using the Response Evaluation Criteria in Solid Tumors criteria. Health related quality of life (HRQOL) was measured using the European Organisation for Research and Treatment of Cancer QLQ-C30 and Lung Module (QLQ-LC13).Results Two hundred fifty patients were randomized: 80% male; median age, 58 years; and WHO PS, 0, 1, 2 in 25, 62, and 13% of cases, respectively. There were no toxic deaths. The main grade 3 or 4 toxicities observed were neutropenia and emesis, reported twice as often in the combination arm. Among 213 patients with measurable disease, response rate was 13.6% (arm A) versus 23.6% (arm B; P =.056). No difference in HRQOL was observed on any of the scales. Median overall and 1-year survival in arms A and B were 8.8 (95% Cl, 7.8 to 10.8) v 11.4 months (95% Cl, 10.1 to 15), respectively, and 40% v 46%, respectively (P =.048).Conclusion A combination of raltitrexed and cisplatin improves overall survival compared with cisplatin alone. This study confirms that a combination of cisplatin and an antifolate is superior to cisplatin alone in patients with MPM, without harmful effect on HRQOL.