A multi-centre randomized, open-label phase II trial of continuous erlotinib plus gemcitabine or gemcitabine as first-line therapy in ECOG PS2 patients with advanced non-small cell lung cancer

Erlotinib and gemcitabine are active in NSCLC and have synergy in other cancers. This study investigated the activity and tolerability of this combination as first-line therapy in ECOG PS 2 patients. Chemotherapy-naïve patients with NSCLC, either stage IIIB (with plural effusion) or stage IV, with measurable disease and ECOG PS 2, and adequate organ function were randomized to receive either erlotinib (150 mg/day p.o.) plus gemcitabine (1000 mg/m(2), days 1, 8, 15, every 4 weeks) in Arm A or gemcitabine monotherapy (Arm B). The primary end-point was progression-free survival. Seventeen patients of a planned 120 patients were randomized (12 males; 16 Caucasians, 4 large cell, 9 adenocarcinoma; 13 former and 1 never smokers); 16 patients received treatment (8 in each arm). The incidence of treatment-related adverse events (AEs) was 8/8 in Arm A and 6/8 in Arm B; most AEs were grade 1 or 2. The most common treatment-related non-hematological AEs were grade 1 or 2 rash (7/8) and diarrhea (7/8) in Arm A. Two patients in Arm A had partial responses, with durations of 16 and 47 weeks, respectively. Overall disease control rate (N=15) was 86% in Arm A versus 50% for the control arm. Erlotinib plus gemcitabine for the treatment of ECOG 2 NSCLC patients warrants further investigation including intermittent erlotinib regimens.