Phase II trial assessing the combination of gemcitabine and cisplatin in advanced non-small cell lung cancer (NSCLC)

Background: There is need for more active and better tolerated combinations in non-small cell lung cancer (NSCLC). The Spanish Lung Cancer Group (SLCG) therefore conducted this phase II study to define the efficacy and toxicity profile of the combination of higher doses than usual of gemcitabine along with cisplatin in patients with advanced NSCLC. Patients and methods: Forty patients with pathologically documented advanced NSCLC were included in this trial (34 men, six women; aged 34-74 years; mean 64 years). Twenty-two patients had unresectable stage IIIB disease and 18 had stage IV disease. Karnofsky performance status was greater than or equal to 70%. In five patients, surgery had previously been performed and four patients had received radiotherapy. Gemcitabine at a dose of 1200 mg/m(2) was administered weekly (days 1, 8 and 15) and cisplatin 100 mg/m(2) on day 15 of each 28-day cycle. Results: Responses were scored according to standard World Health Organization criteria. Of 40 assessable patients, 19 had a partial response for an overall response rate of 47.5% (95% confidence interval (CI) 32-64%). To date, median survival for the whole group is 10.4 months (95% CI 6.2-11.7 months), with a 1-year survival rate of 35%. Toxicity was mainly haematological. Seven patients (18%) had grade 4 neutropenia (one episode of febrile neutropenia). Thrombocytopenia (12.8% grade 3 and 2.6% grade 4) was not associated with clinical bleeding. One patient had a grade 4 transient rise in transaminase. There was no grade 3 or 4 renal toxicity. There was no grade 4 symptomatic toxicity. The most common grade 3 toxicities were nausea and vomiting (28.2%) and alopecia (10.3%) both related to cisplatin. Conclusions: Gemcitabine can be safely administered at a dose of 1200 mg/m(2) in combination with cisplatin. Thrombocytopenia seems to be less than in schedules with cisplatin given on day 1. The results of this study show promising activity (47.5% response rate) with modest toxicity. As this combination of gemcitabine and cisplatin deserves further evaluation in prospective randomized trials, the SLCG is comparing gemcitabine-cisplatin with etoposide-cisplatin in a phase III randomized study. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved.