A randomized phase II trial using two different treatment schedules of gemcitabine and carboplatin in patients with advanced non-small-cell lung cancer

BACKGROUND: Gemcitabine and carboplatin combination therapy is an active and tolerable regimen in the treatment of non-small-cell lung cancer (NSCLC). Twenty-eight- and 21-day regimens without day-15 administration of gemcitabine are common; however, it remains unclear which offers the optimal therapeutic index. METHODS: This trial evaluated two schedules of the combination of gemcitabine and carboplatin: gemcitabine (1100 mg/m on days 1 and 8) plus carboplatin (area under the curve = 5 on day 8) every 28 days, or gemcitabine (1000 mg/m on days 1 and 8) plus carboplatin (area under the curve = 5 on day 1) every 21 days. Eligible patients in this trial had stage IIIB (with malignant pleural effusion) or stage IV NSCLC with no prior chemotherapy. The primary objective was to evaluate progression-free survival, with secondary objectives of overall survival, response rate, and toxicity. RESULTS: One hundred patients were randomized and enrolled from October of 2000 to January of 2002 into this multi-institutional study (48 for the 28-day regimen and 52 for the 21-day regimen). Baseline demographics were well matched, and a majority of patients (85%) enrolled with stage IV disease. Median progression-free survival and response rates were 3.8 months and 22.9%, respectively, with the 28-day regimen, and 4.9 months and 40.4%, respectively, with the 21-day regimen. Median survival was 8.7 months with the 28-day regimen and 8.0 months for the 21-day regimen. One- and 2-year survival rates were 34.7% and 8.7%, respectively, with the 28-day regimen, and 36.5% and 16.8%, respectively, with the 21-day regimen. Differences in progression-free survival (log-rank statistic, p = 0.5786), response rate (Fisher's exact test, p = 0.0859) and overall survival (log-rank statistic, p = 0.3568) were not statistically significant. Grade 3 to 4 hematologic toxicities occurred with a greater frequency in the 21-day regimen. No grade 3 to 4 nonhematologic toxicity (except nausea/vomiting with the 28-day regimen) was observed in more than 10% of patients in either treatment arm. CONCLUSION: Gemcitabine plus carboplatin is active and well tolerated in advanced NSCLC. Both regimens may be considered for further study. Although the 21-day regimen appeared to be associated with preferable outcomes, differences between treatment groups were not statistically significant.