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 toxici ty profile of the combination of higher doses than usual of gemcitabine alo ng with cisplatin in patients with advanced NSCLC. Patients and methods: Fo rty patients with pathologically documented advanced NSCLC were included in this trial (34 men, six women; aged 34-74 years; mean 64 years). Twenty-tw o patients had unresectable stage IIIB disease and 18 had stage IV disease. Karnofsky performance status was greater than or equal to 70%. In five pat ients, surgery had previously been performed and four patients had received radiotherapy. Gemcitabine at a dose of 1200 mg/m(2) was administered weekl y (days 1, 8 and 15) and cisplatin 100 mg/m(2) on day 15 of each 28-day cyc le. Results: Responses were scored according to standard World Health Organ ization 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 haematolog ical. Seven patients (18%) had grade 4 neutropenia (one episode of febrile neutropenia). Thrombocytopenia (12.8% grade 3 and 2.6% grade 4) was not ass ociated 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. Conclusio ns: Gemcitabine can be safely administered at a dose of 1200 mg/m(2) in com bination with cisplatin. Thrombocytopenia seems to be less than in schedule s with cisplatin given on day 1. The results of this study show promising a ctivity (47.5% response rate) with modest toxicity. As this combination of gemcitabine and cisplatin deserves further evaluation in prospective random ized trials, the SLCG is comparing gemcitabine-cisplatin with etoposide-cis platin in a phase III randomized study. (C) 1998 Published by Elsevier Scie nce Ireland Ltd. All rights reserved.