Pemetrexed plus cisplatin or pemetrexed plus carboplatin for chemonaive patients with malignant pleural mesothelioma: Results of the International Expanded Access Program
Pemetrexed plus cisplatin or pemetrexed plus carboplatin for chemonaive patients with malignant pleural mesothelioma: Results of the International Expanded Access Program
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DOI：
10.1097/jto.0b013e31817c73d6
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发表时间：
2008-07-01
影响因子：
20.4
通讯作者：
Manegold, Christian
中科院分区：
文献类型：
--
作者：
Santoro, Armando;O'Brien, Mary E.;Manegold, Christian
简介：先前发表的一项培美曲塞联合顺铂治疗恶性胸膜间皮瘤（MPM）患者的随机III期研究结果显示，与顺铂相比，培美曲塞联合顺铂具有显著的生存获益和更高的缓解率。尽管培美曲塞正在接受监管机构的审查，但国际扩大用药计划（EAP）为13个国家的3000多名间皮瘤患者提供了培美曲塞或培美曲塞单药联合顺铂或卡铂治疗。本文报道了非随机开放标签研究中接受培美曲塞联合铂类药物治疗的化疗无效患者的安全性和有效性数据。方法：组织学证实的MPM患者，不适合根治性手术，接受培美曲塞500 mg/m2联合顺铂75 mg/m2或卡铂AUC 5，每21天一次，标准术前用药。在研究结束时记录疗效数据。结果：共有1704例化疗患者接受培美曲塞+顺铂（n = 843）或培美曲塞+卡铂（n = 861），并进行安全性评价。疗效可评价人群包括培美曲塞+顺铂组的745例患者和培美曲塞+卡铂组的752例患者，医生报告的肿瘤缓解可用。培美曲塞联合顺铂组的缓解率为26.3%，培美曲塞联合卡铂组为21.7%，1年生存率（63.1% vs 64.0%）和中位至疾病进展时间（7个月vs 6.9个月）相似。最常见的3/4级血液学毒性是中性粒细胞减少，培美曲塞加顺铂组为23.9%，培美曲塞加卡铂组为36.1%。结论：这一大型EAP证实了培美曲塞加顺铂和培美曲塞加卡铂在化疗无效的MPM患者中的活性，表现出临床相似的疾病进展时间和1年生存率。
Introduction: Previously published results from a randomized phase III study of pemetrexed plus cisplatin in patients with malignant pleural mesothelioma (MPM) demonstrated a significant survival benefit and higher response rate compared with cisplatin. Although pernetrexed was under review by regulatory agencies, an International Expanded Access Program (EAP) provided more than 3000 mesothelioma patients with access to single-agent pemetrexed or pernetrexed in combination with cisplatin or carboplatin in 13 countries. This manuscript reports the safety and efficacy data from the nonrandomized open-label study in chemonaive patients receiving pernetrexed plus platinum under the EAP.Methods: Patients with histologically confirmed MPM, not amenable to curative surgery, received pemetrexed 500 mg/m(2) in combination with either cisplatin 75 mg/m(2) or carboplatin AUC 5, once every 21 days with standard premedication. Efficacy data were recorded at the end of study participation.Results: A total of 1704 chemonaive patients received pemetrexed plus cisplatin (n = 843) or pemetrexed plus carboplatin (n = 861) and were evaluated for safety. The efficacy evaluable population consisted of 745 patients in the pernetrexed plus cisplatin group and 752 patients in the pemetrexed plus carboplatin group for whom physician-reported tumor response was available. The pemetrexed plus cisplatin group demonstrated a response rate of 26.3% compared with 21.7% for the pernetrexed plus carboplatin group, with similar 1-year survival rates (63.1% versus 64.0%) and median time to progressive disease (7 months versus 6.9 months). The most common grade 3/4 hematologic toxicity was neutropenia in 23.9% of the pernetrexed plus cisplatin group and 36.1% of the pemetrexed plus carboplatin group.Conclusion: This large EAP confirmed the activity of pemetrexed plus cisplatin and pemetrexed plus carboplatin in chemonaive patients with MPM, demonstrating clinically similar time to progressive disease and 1-year survival rates.