Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer

被引:2632
作者
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
[1] Univ Turin, Orbasano, Italy
[2] San Camillo Forlanini Hosp, Rome, Italy
[3] Tata Mem Hosp, Mumbai 400012, Maharashtra, India
[4] Nizams Inst Med Sci, Hyderabad, Andhra Pradesh, India
[5] Bangalore Inst Oncol, Bangalore, Karnataka, India
[6] Asklepios Fachklin Munchen, Gauting, Germany
[7] Heidelberg Univ, Med Ctr, D-6800 Mannheim, Germany
[8] Hosp Grosshansdorf, Grosshansdorf, Germany
[9] Jeroen Bosch Ziekenhuis, sHertogenbosch, Netherlands
[10] Univ Hosp Gasthuisberg, B-3000 Leuven, Belgium
[11] Specjalistyczny Szpital Im, Szczecin, Poland
[12] Maria Sklodowska Curie Mem Inst Oncol, Krakow, Poland
[13] Natl Canc Inst, Rio De Janeiro, Brazil
[14] Natl Canc Ctr, Goyang, South Korea
[15] Samsung Med Ctr, Seoul, South Korea
[16] Herlev Univ Hosp, DK-2730 Herlev, Denmark
[17] Ege Univ, Izmir, Turkey
[18] Eli Lilly & Co, Toronto, ON, Canada
[19] Eli Lilly & Co, Indianapolis, IN 46285 USA
[20] Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA
关键词
D O I
10.1200/JCO.2007.15.0375
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 <= .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.
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页码:3543 / 3551
页数:9
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