Paclitaxel (175 mg/m2) plus carboplatin (6 AUC) versuspaclitaxel (225 mg/m2) plus carboplatin (6 AUC) in advanced non-small-cell lung cancer (NSCLC): A multicenter randomized trial

Purpose:The combination of paclitaxel and carboplatin has becomea widely used regimen in NSCLC due to phase II reports of moderate toxicity,reasonable activity and easy outpatient administration. Purpose of our presentprospective study was to evaluate the dose–response relationship ofpaclitaxel.Patients and methods:Since July 1996, 198 patients withnon-operable NSCLC and measurable disease without previous chemotherapyentered the trial. Ninety nine patients (group A) were randomized to receivepaclitaxel 175 mg/m² in three-hour infusion plus carboplatin dosedto an area under the concentration–time curve of 6 every 3 weeks and 99(group B) to receive the same regimen with paclitaxel increased to 225mg/m². Eligibility criteria included WHO performance status0–2, documented inoperable stage IIIA and IIIB, IV, no brain metastasis,no prior chemotherapy and adequate renal and hepatic function. Patients inboth groups were well-matched with baseline disease characteristics.Results:In group A with 90 evaluable patients, the response ratewas 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. Mediantime to progression favored the high-dose paclitaxel (4.3 vs. 6.4 months,P = 0.044). The median survival was 9.5 months for group A versus11.4 months for group B (P = 0.16). The one-year survival was37% for group A and 44% for group B (P = 0.35). Thebest prognostic factor for one-year survival was the response rate (P< 0.0001). With a relative dose intensity of paclitaxel 0.94 in bothgroups, neurotoxicity (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 toprogression but causes more neurotoxicity and leucopenia. The better responserate, the longer overall and better one-year survival seen with the higherdose of paclitaxel are not statistically significant.