Phase II study of gemcitabine and vindesine in patients with previously untreated non-resectable non-small-cell lung cancer

Abstract

Summary Because both vindesine and gemcitabine are active drugs in advanced non-small-cell lung cancer (NSCLC), with different modes of action and only partly overlapping toxicity, a phase II study was performed. Gemcitabine 1000 mg m -2 was given on days 1, 8 and 15 every 4 weeks, while vindesine 3 mg m -2 was administered weekly for 7 weeks, then every 2 weeks. A total of 42 patients with nonresectable NSCLC were included. The median age of patients was 56 years; 57% were men, 52% had adenocarcinoma, 31% squamous cell carcinoma and 17% had large-cell carcinoma. The performance status ranged from 0 to 2 with 83% in performance status 1. The majority (55%) had stage IV disease, while 40% had stage III B and 5% stage III A disease. WHO grade 3-4 leucopenia occurred in five patients (12%) and 9% had grade 4 neutropenia. Thrombocytopenia grade 3-4 was observed in six patients (15%). There were no septic death or bleeding episodes. One patient had a transient WHO grade 4 increase in bilirubin, and four patients had a decrease in glomerular filtration rate below the normal limit; one of these patients developed a non-reversible renal insufficiency. Ten patients (24%) complained of dyspnoea of uncertain mechanism, possibly involving bronchoconstriction. There were one complete and seven partial responses among 40 assessable patients (20%, 95% confidence limits 9-36%). Median response duration was 31 weeks (range 11-83 weeks) and median survival time 31 weeks (range 2-171 weeks). The current combination of gemcitabine and vindesine does not appear to be promising for further examination because of the toxicity and somewhat disappointing activity.

Gemcitabine (GEM) and Vindesine (VDS) in advanced non-small cell lung cancer (NSCLC): A phase II study in elderly or poor performance status patients

“…Our results contrast with those reported by Sorensen et al [14], who tested GEM and VDS in previously untreated NSCLC patients and reported an overall response rate of 20% and a median survival of 31 weeks, with greater hematological and non-hematological toxicity, and a worse quality of life. However, their schedule consisted of GEM 1000 mg/m 2 on day 1,8 and 15, and VDS 3 mg/m 2 every week for the first 7 weeks and then every other week.…”

“…This variation of the Sorensen regimen [14] was designed to reduce the risk of hematological (neutropenia and thrombocytopenia) and non-hematological toxicity (paresthesias).…”