Combination gemcitabine and oxaliplatin for advanced non small cell lung cancer (NSCLC): An Australian multicenter randomized phase II sequencing trial

Abstract

7244 Background: This multicentre trial examined a combination of Gemcitabine and Oxaliplatin, as developed in a prior phase I study, in patients with advanced NSCLC. In the phase I study the regimen was well tolerated with minimal neurotoxicity. Primary endpoint in this phase II study was efficacy. Limited data exists on the effect of sequencing of gemcitabine with platinum drugs; the sequence of administration was randomized in this study and pharmacokinetics assessed. Methods: Patients with IIIb/IV or recurrent NSCLC were eligible if they had not received prior chemotherapy other than as a neoadjuvant regimen or as part of a definitive chemoradiation schedule. Patients had to be WHO PS ≤ 2, have estimated minimum life expectancy of 12 weeks, and have measurable disease by RECIST criteria. Treatment was open label and comprised Gemcitabine (1250mg/m2) and Oxaliplatin (70mg/m2), each given day 1 and day 8 q 21 days. Patients were randomized 1:1 to the sequencing of the two drugs for the duration of the study: Gem → Oxali or Oxali → Gem. Bloods for PK analysis were taken during cycle 1. Patients were formally assessed every two cycles (maximum 6 cycles). Primary endpoint was response rate (RR). Secondary endpoints were progression-free survival, overall survival, toxicity profile and the effect of drug sequencing on toxicity, efficacy and pharmacokinetics. Results: 46 patients were enrolled in 12 months across 6 sites; 43 were evaluable for response. The RR was 26% incorporating 11/43 patients with PR as best response. PFS was 4.3 mths, and OS was 6.7 mths (95% CI 4.4 - 10.1). Toxicity was mild; notably there was little neurosensory toxicity despite a median oxaliplatin dose in excess of 500mg/m2 (1 case of grade 3 neurosensory toxicity). With regards to sequencing of agents no appreciable differences in clinical endpoints of efficacy or safety were observed. Conclusions: This Oxaliplatin/Gemcitabine regimen has shown activity in advanced NSCLC. The toxicities of established Cisplatin and Carboplatin-based ‘doublet’ regimens are well documented. The favorable toxicity profile of this doublet, in light of comparable tumour response rate, warrants its further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Lilly Oncology, Sanofi Lilly Oncology Lilly Oncology Lilly Oncology