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Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2

Clinical Trial

. 2013 Aug 10;31(23):2849-53. doi: 10.1200/JCO.2012.48.1911. Epub 2013 Jun 17. Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2 Carlos H BarriosJose Rodrigues PereiraRonaldo De Albuquerque RibeiroCarlos Augusto de Mendonça BeatoYeni Neron do NascimentoAndre MuradFabio A FrankeMaristela PrecivaleLuiz Henrique de Lima AraujoClarissa Serodio Da Rocha BaldottoFernando Meton VieiraIsabele A SmallCarlos G FerreiraRogerio C Lilenbaum

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Clinical Trial

Randomized phase III trial of single-agent pemetrexed versus carboplatin and pemetrexed in patients with advanced non-small-cell lung cancer and Eastern Cooperative Oncology Group performance status of 2

Mauro Zukin et al. J Clin Oncol. 2013.

. 2013 Aug 10;31(23):2849-53. doi: 10.1200/JCO.2012.48.1911. Epub 2013 Jun 17. Authors Mauro Zukin  1 Carlos H BarriosJose Rodrigues PereiraRonaldo De Albuquerque RibeiroCarlos Augusto de Mendonça BeatoYeni Neron do NascimentoAndre MuradFabio A FrankeMaristela PrecivaleLuiz Henrique de Lima AraujoClarissa Serodio Da Rocha BaldottoFernando Meton VieiraIsabele A SmallCarlos G FerreiraRogerio C Lilenbaum Affiliation

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Abstract

Purpose: To compare single-agent pemetrexed (P) versus the combination of carboplatin and pemetrexed (CP) in first-line therapy for patients with advanced non-small-cell lung cancer (NSCLC) with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2.

Patients and methods: In a multicenter phase III randomized trial, patients with advanced NSCLC, ECOG PS of 2, any histology at first and later amended to nonsquamous only, no prior chemotherapy, and adequate organ function were randomly assigned to P alone (500 mg/m(2)) or CP (area under the curve of 5 and 500 mg/m(2), respectively) administered every 3 weeks for a total of four cycles. The primary end point was overall survival (OS).

Results: A total of 205 eligible patients were enrolled from eight centers in Brazil and one in the United States from April 2008 to July 2011. The response rates were 10.3% for P and 23.8% for CP (P = .032). In the intent-to-treat population, the median PFS was 2.8 months for P and 5.8 months for CP (hazard ratio [HR], 0.46; 95% CI, 0.35 to 0.63; P < .001), and the median OS was 5.3 months for P and 9.3 months for CP (HR, 0.62; 95% CI, 0.46 to 0.83; P = .001). One-year survival rates were 21.9% and 40.1%, respectively. Similar results were seen when patients with squamous disease were excluded from the analysis. Anemia (grade 3, 3.9%; grade 4, 11.7%) and neutropenia (grade 3, 1%; grade 4, 6.8%) were more frequent with CP. There were four treatment-related deaths in the CP arm.

Conclusion: Combination chemotherapy with CP significantly improves survival in patients with advanced NSCLC and ECOG PS of 2.

Trial registration: ClinicalTrials.gov NCT01836575.

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