Erlotinib in combination with pemetrexed for patients with advanced non-small-cell lung cancer (NSCLC): a phase I dose-finding study.

BACKGROUND Erlotinib and pemetrexed are approved single agents for second-line treatment of non-small-cell lung cancer (NSCLC) and, in combination, have shown synergistic antitumor activity in NSCLC cell lines. We investigated the safety, pharmacokinetics and preliminary efficacy of combined erlotinib-pemetrexed in patients with refractory advanced NSCLC. PATIENTS AND METHODS A nonrandomized, open-label, phase IB study was performed in patients with advanced NSCLC whose disease had progressed on or following first-line chemotherapy with a platinum-containing regimen or for whom the erlotinib-pemetrexed combination was considered appropriate. Patients received i.v. pemetrexed 500-700 mg/m² every 3 weeks and oral erlotinib 100-150 mg/day. RESULTS Twenty patients were recruited. The most common adverse events (AEs) were rash, diarrhea and fatigue. Serious AEs occurred in eight patients (three treatment related) and there were eight deaths (none treatment related). Dose-limiting toxic effects were not experienced up to erlotinib 150 mg/day plus pemetrexed 600 mg/m². Concurrent administration did not affect pharmacokinetic parameters. Two patients achieved partial responses and nine had stable disease. CONCLUSIONS Erlotinib-pemetrexed combination is well tolerated at doses equal to the licensed single-agent doses (150 mg/day and 500 mg/m², respectively). The good tolerability profile and promising efficacy indicate that this combination warrants further investigation for patients with advanced NSCLC.