Articles www.thelancet.com Vol 378 September 17, 2011 1079 Lancet 2011; 378: 1079–88 Published Online August 9, 2011 DOI:10.1016/S0140- 6736(11)60780-0 See Comment page 1055 Service de Pneumologie, Hôpitaux Universitaires de Strasbourg, Université de Strasbourg, Strasbourg, France (Prof E Quoix MD); Service de Pneumologie CHU de Caen, Caen, Université de Caen Basse-Normandie, Caen, France (Prof G Zalcman MD); Service de Pneumologie de l’Hôpital de Colmar, Colmar, France (J-P Oster MD); Service de Pneumologie, CHU de Besançon, Besançon, France (Prof V Westeel MD); Service de Pneumologie, CHRU de Tours, Tours, France (E Pichon MD); Service de Pneumologie, Hôpital Tenon, Paris, France (A Lavolé MD, B Milleron MD); Service d’Oncologie Médicale, Hôpital Layné, Mont-de-Marsan, France (J Dauba MD); Service de Pneumologie, Centre Hospitalier Paul Morel, Vesoul, France (D Debieuvre MD); Service de Pneumologie-Centre Hospitalier Lyon-Sud, Pierre-Bénite, France (P-J Souquet MD); Service de Pneumologie, Hôpital Larrey, Toulouse, France (L Bigay-Game MD); Département d’Oncologie Médicale, Centre Oscar Lambret, Lille, France (E Dansin MD); Centre Antoine Lacassagne, Nice, France (M Poudenx MD); Service des Maladies Respiratoires, Centre Hospitalier, Le Mans, France (O Molinier MD); Service des Maladies Respiratoires, Hôpital d’Instruction des Armées Percy, Clamart, France (F Vaylet MD); Carboplatin and weekly paclitaxel doublet chemotherapy compared with monotherapy in elderly patients with advanced non-small-cell lung cancer: IFCT-0501 randomised, phase 3 trial Elisabeth Quoix, Gérard Zalcman, Jean-Philippe Oster, Virginie Westeel, Eric Pichon, Armelle Lavolé, Jérôme Dauba, Didier Debieuvre, Pierre-Jean Souquet, Laurence Bigay-Game, Eric Dansin, Michel Poudenx, Olivier Molinier, Fabien Vaylet, Denis Moro-Sibilot, Dominique Herman, Jaafar Bennouna, Jean Tredaniel, Alain Ducoloné, Marie-Paule Lebitasy, Laurence Baudrin, Silvy Laporte, Bernard Milleron, on behalf of Intergroupe Francophone de Cancérologie Thoracique Summary Background Platinum-based doublet chemotherapy is recommended to treat advanced non-small-cell lung cancer (NSCLC) in fit, non-elderly adults, but monotherapy is recommended for patients older than 70 years. We compared a carboplatin and paclitaxel doublet chemotherapy regimen with monotherapy in elderly patients with advanced NSCLC. Methods In this multicentre, open-label, phase 3, randomised trial we recruited patients aged 70–89 years with locally advanced or metastatic NSCLC and WHO performance status scores of 0–2. Patients received either four cycles (3 weeks on treatment, 1 week off treatment) of carboplatin (on day 1) plus paclitaxel (on days 1, 8, and 15) or five cycles (2 weeks on treatment, 1 week off treatment) of vinorelbine or gemcitabine monotherapy. Randomisation was done centrally with the minimisation method. The primary endpoint was overall survival, and analysis was done by intention to treat. This trial is registered, number NCT00298415. Findings 451 patients were enrolled. 226 were randomly assigned monotherapy and 225 doublet chemotherapy. Median age was 77 years and median follow-up was 30·3 months (range 8·6–45·2). Median overall survival was 10·3 months for doublet chemotherapy and 6·2 months for monotherapy (hazard ratio 0·64, 95% CI 0·52–0·78; p<0·0001); 1-year survival was 44·5% (95% CI 37·9–50·9) and 25·4% (19·9–31·3), respectively. Toxic effects were more frequent in the doublet chemotherapy group than in the monotherapy group (most frequent, decreased neutrophil count (108 [48·4%] vs 28 [12·4%]; asthenia 23 [10·3%] vs 13 [5·8%]). Interpretation Despite increased toxic effects, platinum-based doublet chemotherapy was associated with survival benefits compared with vinorelbine or gemcitabine monotherapy in elderly patients with NSCLC. We feel that the current treatment paradigm for these patients should be reconsidered. Funding Intergroupe Francophone de Cancérologie Thoracique, Institut National du Cancer. Introduction Lung cancer is the leading cause of cancer-related death in men worldwide 1 and in women in the USA it has been the leading cause since 1987. 2 A substantial increase in life expectancy in the general population, with its concomitant increase in the risk of cancer, has led to a notable rise in the incidence of lung cancer in elderly people. As a result, median ages at diagnosis of lung cancer in developed countries are currently 63–70 years. 3–5 Elderly people are under-represented in clinical trials 6,7 and, therefore, might not receive the most appropriate treatment in practice, possibly because of the pessimism of the doctors, patients, and their relatives about the relevance of treatment or drug-related toxic effects. 8 As a consequence, the proportion that receives first- line chemotherapy is small. In one study in the USA, among 21 285 patients aged 66 years or older and diag- nosed in 1997–2002 as having advanced non-small-cell lung cancer (NSCLC), only 5492 (25·8%) received first- line chemotherapy. 9 A randomised trial of chemotherapy with vinorelbine compared with best supportive care in patients aged 70 years or older who had advanced NSCLC showed better results in the vinorelbine group. 10 In the same group of elderly patients, however, combined vinorelbine and gemcitabine did not yield better results than either agent alone. 11 Consequently, the 2004 American Society of Clinical Oncology guidelines, 12 recommended monotherapy in elderly patients with advanced NSCLC, 12 whereas in younger patients with performance status scores of 0–1, platinum-based doublet chemotherapy was recommended as the first-line treat- ment. Post-hoc subgroup analyses of elderly patients in phase 3 trials have suggested, however, that overall survival after combined chemotherapy in carefully selected subgroups of elderly patients can be similar to those in younger patients. 13–15 In a phase 2 trial of a 4-week cycle in which patients received 90 mg/m² paclitaxel on