Pemetrexed + carboplatin versus gemcitabine + carboplatin in the treatment of stage IIIB/IV non-small cell lung cancer

Abstract

7517 Background: A prospective, randomized, multicentre study was conducted to compare pemetrexed + carboplatin (PC) with a standard regimen, gemcitabine + carboplatin (GC). Methods: Chemonaive patients with verified non-small cell lung cancer, stage IIIB (ineligible for curative radiotherapy) or stage IV, WHO performance status (PS) 0–2, adequate hematology and creatinine-clearance > 45 ml/min were eligible. All patients were supplemented with folic acid 0.4 mg OD and vitamin B12 1 mg IM every 9 weeks, from >= 5 days before and through the treatment period. Patients were randomized to receive either pemetrexed 500 mg/m2 + carboplatin AUC=5 (Calvert) day 1 or gemcitabine 1,000 mg/m2 day 1 & 8 + carboplatin AUC=5 (Calvert) day 1. Maximum 4 courses every 3 weeks were given. Primary endpoints: QoL defined as global health status, nausea/vomiting, dyspnea and fatigue - measured by the EORTC QLQ-C30 and LC13 before every cycle and 3 & 11 weeks after the last cycle. Secondary endpoints: Overall survival (OS) and toxicity measured by the CTCAE v3.0. Stratification was done for age (−75 vs +75 years), stage (IIIB vs IV) and PS (0–1 vs 2). 190 evaluable patients in each arm were required to detect a 15% improvement on predefined QoL parameters with an a of 0.05 and β of 0.80. A 15% loss to follow up was expected. Results: 446 patients were included from Apr 05 - Jul 06. The two arms were well balanced with respect to age, sex, stage, PS and histological classification. 436 patients were eligible for the primary QoL-analyses. No statistical significant differences in mean score of the QoL-scales were observed between the arms. So far, 384 patients have been analysed for toxicity. Significantly more patients in the GC arm experienced grade 3–4 thrombocytopenia (48 vs 107, p<0.001), leucopenia (44 vs 89, p<0.001) and granulocytopenia (78 vs 98, p=0.02). No difference in the frequency of neutropenic fever was recorded. More patients in the GC arm received transfusion of platelets (5 vs 19, p=0.02). At present, 291 patients are deceased. We expect to present complete OS analyses for a minimum of 380 patients at the annual meeting. Conclusions: No differences were detected between the two arms with respect to the primary QoL outcome. Patients in the PC arm experienced less toxicity. No significant financial relationships to disclose.