一项III期研究，比较顺铂加吉西他滨与顺铂加培美曲塞用于初治晚期非小细胞肺癌患者的化疗效果。
Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer.
作者信息
Scagliotti Giorgio Vittorio, Parikh Purvish, von Pawel Joachim, Biesma Bonne, Vansteenkiste Johan, Manegold Christian, Serwatowski Piotr, Gatzemeier Ulrich, Digumarti Raghunadharao, Zukin Mauro, Lee Jin S, Mellemgaard Anders, Park Keunchil, Patil Shehkar, Rolski Janusz, Goksel Tuncay, de Marinis Filippo, Simms Lorinda, Sugarman Katherine P, Gandara David
机构信息
University of Torino, Department of Clinical and Biological Sciences, S. Luigi Hospital, Regione Gonzole, 10, Orbassano (Torino), Italy.
出版信息
J Clin Oncol. 2008 Jul 20;26(21):3543-51. doi: 10.1200/JCO.2007.15.0375. Epub 2008 May 27.
PURPOSE
Cisplatin plus gemcitabine is a standard regimen for first-line treatment of advanced non-small-cell lung cancer (NSCLC). Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting.
PATIENTS AND METHODS
This noninferiority, phase III, randomized study compared the overall survival between treatment arms using a fixed margin method (hazard ratio [HR] < 1.176) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1. Patients received cisplatin 75 mg/m(2) on day 1 and gemcitabine 1,250 mg/m(2) on days 1 and 8 (n = 863) or cisplatin 75 mg/m(2) and pemetrexed 500 mg/m(2) on day 1 (n = 862) every 3 weeks for up to six cycles.
RESULTS
Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine (median survival, 10.3 v 10.3 months, respectively; HR = 0.94; 95% CI, 0.84 to 1.05). Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma (n = 847; 12.6 v 10.9 months, respectively) and large-cell carcinoma histology (n = 153; 10.4 v 6.7 months, respectively). In contrast, in patients with squamous cell histology, there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed (n = 473; 10.8 v 9.4 months, respectively). For cisplatin/pemetrexed, rates of grade 3 or 4 neutropenia, anemia, and thrombocytopenia (P <or= .001); febrile neutropenia (P = .002); and alopecia (P < .001) were significantly lower, whereas grade 3 or 4 nausea (P = .004) was more common.
CONCLUSION
In advanced NSCLC, cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine. This is the first prospective phase III study in NSCLC to show survival differences based on histologic type.
目的
顺铂联合吉西他滨是晚期非小细胞肺癌（NSCLC）一线治疗的标准方案。培美曲塞联合铂类化合物的II期研究也显示在此情况下有活性。
患者与方法
这项非劣效性、III期随机研究采用固定界值法（风险比[HR]<1.176）比较了1725例未经化疗、IIIB期或IV期NSCLC且东部肿瘤协作组体能状态为0至1的患者治疗组之间的总生存期。患者在第1天接受顺铂75mg/m²，在第1天和第8天接受吉西他滨1250mg/m²（n = 863），或在第1天接受顺铂75mg/m²和培美曲塞500mg/m²（n = 862），每3周一次，最多六个周期。
结果
顺铂/培美曲塞的总生存期不劣于顺铂/吉西他滨（中位生存期分别为10.3个月和10.3个月；HR = 0.94；95%CI，0.84至1.05）。在腺癌患者（n = 847；分别为12.6个月和10.9个月）和大细胞癌组织学类型患者（n = 153；分别为10.4个月和6.7个月）中，顺铂/培美曲塞的总生存期在统计学上优于顺铂/吉西他滨。相比之下，在鳞状细胞组织学类型患者中，顺铂/吉西他滨对比顺铂/培美曲塞的生存期有显著改善（n = 473；分别为10.8个月和9.4个月）。对于顺铂/培美曲塞，3级或4级中性粒细胞减少、贫血和血小板减少的发生率（P≤0.001）；发热性中性粒细胞减少（P = 0.002）；以及脱发（P<0.001）显著更低，而3级或4级恶心（P = 0.004）更常见。
结论
在晚期NSCLC中，顺铂/培美曲塞与顺铂/吉西他滨疗效相似，但耐受性更好且给药更方便。这是NSCLC中第一项基于组织学类型显示生存差异的前瞻性III期研究。
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