Concomitant chemoradiotherapy using pemetrexed and carboplatin for unresectable stage III non-small cell lung cancer (NSCLC): preliminary results of a phase II study.

BACKGROUND: Concomitant chemoradiotherapy is the standard treatment of unresectable stage III non-small cell lung cancer (NSCLC). However, the optimal chemotherapy regimen is still controversial. We have conducted a phase II clinical trial in a Chinese population to evaluate concomitant treatment using pemetrexed/carboplatin chemotherapy and thoracic radiotherapy followed by pemetrexed/carboplatin consolidation chemotherapy in these patients. The purpose of this study is to evaluate the feasibility and activity, and also assess its impact on progression-free survival (PFS).

PATIENTS AND METHODS: A total of 21 patients were enrolled between January 2008 and October 2009. Patients received concomitant pemetrexed 500 mg/m(2), carboplatin area under the curve (AUC) 5 chemotherapy on day 1 repeated every 3 weeks for 2 cycles and thoracic radiotherapy, followed by pemetrexed/carboplatin for 3 cycles as consolidation therapy. Objective response rate according to the RECIST criteria was recorded and toxicity was evaluated using the NCI Common Toxicity Criteria. The Kaplan-Meier method was used to evaluate patient survival. Univariate analysis of patient characteristics and tumor responses was conducted using the Chi-square and Fisher's exact test.

RESULTS: Five (23.8%) and 13 patients (61.9%) had a complete or partial response, respectively, while 2 patient's disease remained stable and 1 patient had progression of the disease. The overall response rate (85.7%, 95% confidence interval (CI): 61-97%) exceeded the goal per study design. The median PFS was 12.0 months (95% CI: 10.6-13.4 months). The statistical analysis of predictive factors of efficacy revealed that the response rate and PFS seemed to a trend favoring adenocarcinoma histology. Main toxicity (grade 3 or greater, %): neutropenia 6 (28.5%); thrombocytopenia 4 (19%); anaemia 5 (23.8%); nausea/vomiting 1 (4.8%); anorexia 1 (4.8%), dysphagia 2 (9.5%), radiation pneumonitis 1 (4.8%) and fatigue 2 (9.5%).

CONCLUSION: This data suggests that concomitant treatment with pemetrexed/carboplatin at full systemic doses and thoracic radiotherapy was well tolerated, with promising activity in a Chinese population with unresectable stage III NSCLC. Better outcomes were observed in patients with adenocarcinoma in this study. Although the data presented herewith appears promising, this study is relatively small, and more data from randomized trials are needed to further validate this regimen.