Vogelzang Nicholas J, Rusthoven James J, Symanowski James, Denham Claude, Kaukel E, Ruffie Pierre, Gatzemeier Ulrich, Boyer Michael, Emri Salih, Manegold Christian, Niyikiza Clet, Paoletti Paolo
University of Chicago, Cancer Research Center, 5841 South Maryland Ave, Chicago, IL 60637, USA.
J Clin Oncol. 2003 Jul 15;21(14):2636-44. doi: 10.1200/JCO.2003.11.136.
Patients with malignant pleural mesothelioma, a rapidly progressing malignancy with a median survival time of 6 to 9 months, have previously responded poorly to chemotherapy. We conducted a phase III trial to determine whether treatment with pemetrexed and cisplatin results in survival time superior to that achieved with cisplatin alone.
Chemotherapy-naive patients who were not eligible for curative surgery were randomly assigned to receive pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 on day 1, or cisplatin 75 mg/m2 on day 1. Both regimens were given intravenously every 21 days.
A total of 456 patients were assigned: 226 received pemetrexed and cisplatin, 222 received cisplatin alone, and eight never received therapy. Median survival time in the pemetrexed/cisplatin arm was 12.1 months versus 9.3 months in the control arm (P =.020, two-sided log-rank test). The hazard ratio for death of patients in the pemetrexed/cisplatin arm versus those in the control arm was 0.77. Median time to progression was significantly longer in the pemetrexed/cisplatin arm: 5.7 months versus 3.9 months (P =.001). Response rates were 41.3% in the pemetrexed/cisplatin arm versus 16.7% in the control arm (P <.0001). After 117 patients had enrolled, folic acid and vitamin B12 were added to reduce toxicity, resulting in a significant reduction in toxicities in the pemetrexed/cisplatin arm.
Treatment with pemetrexed plus cisplatin and vitamin supplementation resulted in superior survival time, time to progression, and response rates compared with treatment with cisplatin alone in patients with malignant pleural mesothelioma. Addition of folic acid and vitamin B12 significantly reduced toxicity without adversely affecting survival time.
恶性胸膜间皮瘤患者病情进展迅速，中位生存时间为6至9个月，此前对化疗反应不佳。我们进行了一项III期试验，以确定培美曲塞和顺铂联合治疗是否能带来优于单纯顺铂治疗的生存时间。
未接受过化疗且不符合根治性手术条件的患者被随机分配，一组在第1天接受培美曲塞500mg/m²和顺铂75mg/m²，另一组在第1天仅接受顺铂75mg/m²。两种方案均每21天静脉给药一次。
总共分配了456例患者：226例接受培美曲塞和顺铂联合治疗，222例仅接受顺铂治疗，8例未接受任何治疗。培美曲塞/顺铂组的中位生存时间为12.1个月，而对照组为9.3个月（P = 0.020，双侧对数秩检验）。培美曲塞/顺铂组患者死亡的风险比相对于对照组为0.77。培美曲塞/顺铂组的中位疾病进展时间明显更长：5.7个月对3.9个月（P = 0.001）。培美曲塞/顺铂组的缓解率为41.3%，而对照组为16.7%（P < 0.0001）。在117例患者入组后，添加了叶酸和维生素B12以降低毒性，培美曲塞/顺铂组的毒性显著降低。
与单纯顺铂治疗相比，培美曲塞联合顺铂及维生素补充剂治疗可使恶性胸膜间皮瘤患者获得更长的生存时间、疾病进展时间和更高的缓解率。添加叶酸和维生素B12可显著降低毒性，且不影响生存时间。
