Paclitaxel (175 mg/m(2)) plus carboplatin (6 AUC) versus paclitaxel (225 mg/m(2))plus carboplatin (6 AUG) in advanced non-small-cell lung cancer (NSCLC): A multicenter randomized trial

Purpose: The combination of paclitaxel and carboplatin has become a widely used regimen in NSCLC due to phase II reports of moderate toxicity, reasona ble activity and easy outpatient administration. Purpose of our present pro spective study was to evaluate the dose-response relationship of paclitaxel . Patients and methods: Since July 1996, 198 patients with non-operable NSCLC and measurable disease without previous chemotherapy entered the trial. Ni nety nine patients (group A) were randomized to receive paclitaxel 175 mg/m (2) in three-hour infusion plus carboplatin dosed to an area under the conc entration-time curve of 6 every 3 weeks and 99 (group B) to receive the sam e regimen with paclitaxel increased to 225 mg/m(2). Eligibility criteria in cluded WHO performance status 0-2, documented inoperable stage IIIA and III B, IV, no brain metastasis, no prior chemotherapy and adequate renal and he patic function. Patients in both groups were well-matched with baseline dis ease characteristics. Results. In group A with 90 evaluable patients, the response rate was 25.6% (6 CR, 17 PR) whereas in group B with 88 evaluable patients, the response rate was 31.8% (3 CR, 25 PR), P = 0.733. Median time to progression favored the high-dose paclitaxel (4.3 vs. 6.4 months, P = 0.044). The median survi val was 9.5 months for group A versus 11.4 months for group B (P = 0.16). T he one-year survival was 37% for group A and 44% for group B (P = 0.35). Th e best prognostic factor for one-year survival was the response rate (P < 0 .0001). With a relative dose intensity of paclitaxel 0.94 in both groups, n eurotoxicity (P = 0.025) and leucopenia (P = 0.038) were more pronounced in group B patients. No toxic death was observed. Conclusions: Higher dose paclitaxel prolongs the median time to progression but causes more neurotoxicity and leucopenia. The better response rate, th e longer overall and better one-year survival seen with the higher dose of paclitaxel are not statistically significant.