Santoro Armando, O'Brien Mary E, Stahel Rolf A, Nackaerts Kristiaan, Baas Paul, Karthaus Meinolf, Eberhardt Wilfried, Paz-Ares Luis, Sundstrom Stein, Liu Yushan, Ripoche Veronique, Blatter Johannes, Visseren-Grul Carla M, Manegold Christian
Istituto Clinico Humanitas, Rozzano, Italy.
J Thorac Oncol. 2008 Jul;3(7):756-63. doi: 10.1097/JTO.0b013e31817c73d6.
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 pemetrexed 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 pemetrexed in combination with cisplatin or carboplatin in 13 countries. This manuscript reports the safety and efficacy data from the nonrandomized open-label study in chemonaïve patients receiving pemetrexed plus platinum under the EAP.
Patients with histologically confirmed MPM, not amenable to curative surgery, received pemetrexed 500 mg/m in combination with either cisplatin 75 mg/m or carboplatin AUC 5, once every 21 days with standard premedication. Efficacy data were recorded at the end of study participation.
A total of 1704 chemonaïve 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 pemetrexed 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 pemetrexed 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 pemetrexed plus cisplatin group and 36.1% of the pemetrexed plus carboplatin group.
This large EAP confirmed the activity of pemetrexed plus cisplatin and pemetrexed plus carboplatin in chemonaïve patients with MPM, demonstrating clinically similar time to progressive disease and 1-year survival rates.
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期研究结果表明,与顺铂相比,其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,但一项国际扩大可及项目(EAP)在13个国家为3000多名间皮瘤患者提供了使用单药培美曲塞或培美曲塞联合顺铂或卡铂的机会。本手稿报告了在EAP下接受培美曲塞加铂类药物治疗的初治患者的非随机开放标签研究的安全性和疗效数据。
组织学确诊为MPM且不宜进行根治性手术的患者,接受培美曲塞500mg/m²联合顺铂75mg/m²或卡铂AUC 5,每21天一次,并给予标准预处理。在研究参与结束时记录疗效数据。
共有1704例初治患者接受了培美曲塞联合顺铂(n = 843)或培美曲塞联合卡铂(n = 861)治疗,并进行了安全性评估。疗效可评估人群包括培美曲塞联合顺铂组的745例患者和培美曲塞联合卡铂组的752例患者,这些患者有医生报告的肿瘤反应数据。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年生存率相似(63.1%对64.0%),疾病进展中位时间相似(7个月对6.9个月)。最常见的3/4级血液学毒性是中性粒细胞减少,培美曲塞联合顺铂组为23.9%,培美曲塞联合卡铂组为36.1%。
这项大型EAP证实了培美曲塞联合顺铂和培美曲塞联合卡铂在初治MPM患者中的活性,显示出疾病进展时间和1年生存率在临床上相似。