Induction chemotherapy with gemcitabine-carboplatin-paclitaxel (GEMCAP) in stage III non-small cell lung cancer (NSCLC).

Abstract

7063 Background: The addition of gemcitabine (G) to doublet chemotherapy with carboplatin (C) and paclitaxel (P) has demonstrated to improve clinical outcome of advanced stage IIIB and IV NSCLC in a phase II-III study, albeit with significant hematologic toxicity. In a previous dose finding study, we identified a safe GEMCAP regimen based on dose-limiting toxicities. Methods: Patients aged 18-75 years, with ECOG PS 0-1, and unresectable clinical stage IIIA NSCLC, or stage IIIB suitable for definitive radiation treatment were treated in a phase II study with C AUC 5 i.v., P 175 mg/m2 i.v. on day 1, and G 800 mg/m2 i.v. on days 1 and 8, every 3 weeks for 3 cycles. Patients with stage IIIA disease in response following GEMCAP were reassessed for surgery; those with unresectable stage IIIA disease and stage IIIB, were treated with radiotherapy. Primary endpoint was response rate. Secondary endpoints included: toxicity, progression-free survival (PFS), resection rate, and overall survival (OS). Results: Of the 53 enrolled patients, 42 were males, 11 females, 29 (55%) had stage IIIA, 24 (45%) stage IIIB NSCLC, 47 (89%) had a PS 0. Forty partial responses and one complete response were observed, for an overall response rate of 80%. G3-4 and G2 toxicities, occurring in ≥ 5% of patients, included: neutropenia (19-8%), hypertransaminemia (11-2%), diarrhoea (6-0%), G3-4 toxicities; neutropenia (34%), asthenia (25%), diarrhoea (15%), peripheral neuropathy (13%), osteomialgya (11%), hypertransaminemia (6%), nausea/vomiting (9%), G2 toxicity. With a median follow-up of 20 months (range, 6-77) PFS was 10.5 months (95% CI, 9.9-11.4); OS was 21.1 months (95% CI, 19.6-22.9). Thirteen patients were operated, for a resection rate of 44%. Conclusions: The GEMCAP regimen at the dose employed produced high response and resection rate, with acceptable toxicity, as induction chemotherapy for clinical stage III NSCLC. PFS and OS compared favourably with that expected for clinical stage III disease.