Phase I/II dose finding study of paclitaxel and carboplatin in advanced non-small cell lung cancer

Abstract

Introduction: This phase I study was designed to establish the maximum tolerated dose (MTD) of the carboplatin–paclitaxel combination, given without routine growth factor support to previously untreated patients with stage IIIB and IV non-small cell lung cancer. Patients and methods: Fifty patients (one stage IIIa, 31 stage IIIb and 18 stage IV) were sequentially assigned to one of 14 treatment groups in which paclitaxel and carboplatin were administered in doses ranging from 130 to 235 mg/m 2 and from 230 to 375 mg/m 2 , respectively. Paclitaxel was administered as a 3-h intravenous infusion using non-polyvinylchloride tubing and connectors. The carboplatin infusion, over 30 min, was administered at the completion of the paclitaxel infusion. Results: The MTD for the combination has been reached at 235 mg/m 2 of paclitaxel and at 375 mg/m 2 of carboplatin. The combination shows a good safety profile with very few and brief episodes of neutropenia without any infectious episodes. At the doses tested thrombocytopenia did not occur at all. Among 47 assessable patients there was one complete response and 17 partial responses for an overall response rate of 38%. There has been a tendency to a dose–response relationship for the combination with only six partial responses (27%) reported in 22 patients who received paclitaxel at doses ≤195 mg/m 2 and carboplatin at doses <350 mg/m 2 and 12 partial responses in 25 patients (48%) receiving paclitaxel >195 mg/m 2 and carboplatin ≥350 mg/m 2, respectively. The median event-free survival time is 33 weeks (range, 4–156+). With a minimum follow up duration of 57 weeks the median overall survival time is 51.81 weeks (range, 7–162+) and the 1-year survival rate is 49%. Conclusion: In advanced NSCLC the carboplatin–paclitaxel combination can be safely administered at the doses of 375 and 225 mg/m 2 every 4 weeks, it appears to be active and well tolerated.