Purpose: Gemcitabine and vinorelbine have demonstrated clinical efficacy both as single agents and in combination in patients with metastatic non-small cell lung cancer (NSCLC). This phase II trial evaluated biweekly gemcitabine and vinorelbine in NSCLC patients who have had one prior chemotherapeutic regimen and have had disease progression.
Methods: Gemcitabine (1,200 mg/m(2) IV over 30 min) was followed by vinorelbine (30 mg/m(2) IV over 6-10 min) on days 1 and 15 of each 28 day cycle. Chemotherapy was given for six cycles unless disease progression or unacceptable toxicity was seen.
Results: From 11/1998 to 10/2000, 15 of 20 patients enrolled (6 males, 9 females) were evaluable for response and survival. Two patients had grade 4 neutropenia, and one patient had grade 4 thrombocytopenia. The only non-hematologic grade 3 toxicities were fatigue, phlebitis, and arthralgias. No objective responses were observed, but 11 patients had stable disease for a mean of 6 months. The median survival time was 9.4 months (95% CI = 4.2, 14.8), with a median time to progression of 4.2 months (95% CI = 1.9, 5.6). The 1 year survival was 47%.
Conclusions: While this schedule of gemcitabine and vinorelbine was well tolerated, it was felt to be inactive. In vitro and pharmacokinetic studies published after the completion of our trial, suggest gemcitabine followed by vinorelbine may have antagonistic effects leading to lower dose delivery of both drugs. Our study was the only study of gemcitabine and vinorelbine in second-line NSCLC in the literature without an objective response. Our study was the only second-line study that administered gemcitabine prior to vinorelbine. First-line studies in the literature that administered vinorelbine prior to gemcitabine had, on average, a 1.7 month higher median survival (10.0 vs. 8.3 mos; P value <0.001). Because of the lack of response, further studies using this drug sequence, dose, and schedule for gemcitabine and vinorelbine are not recommended.