A Phase I/Ii Study Of Biweekly Carboplatin And Nab-Paclitaxel With Concurrent Radiotherapy For Patients With Locally Advanced Unresectable Stage Iii Non-Small-Cell Lung Cancer

Concurrent chemoradiotherapy is the standard treatment for patients with locally advanced non---small-cell lung cell cancer (LA-NSCLC). However, the optimal regimen has not been determined. We conducted the phase MI study of biweekly carboplatin and nab-paclitaxel with radiotherapy in patients with LA-NSCLC. This regimen was well-tolerated and exerted promising antitumor activity for patients with LA-NSCLC.Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for patients with locally advanced non-small-cell lung cell cancer (LA-NSCLC). We conducted a phase I/II study of biweekly carboplatin and nabpaclitaxel (nab-PTX) with radiotherapy (RT). Materials and Methods: In the phase I part, patients with inoperable stage IIIA/IIIB NSCLC were treated with carboplatin (area under the time-concentration curve, 4) and nab-PTX (60-100 mg/m(2)) on days 1, 15, and 29. Thoracic RT was administered from day 1 to a total dose of 60 Gy in 30 fractions. In the phase II part, patients were administered carboplatin and nab-PTX on days 1, 15, and 29 at the recommended dose (RD). The primary endpoint of the phase I part was to determine the maximum tolerated dose and the RD. In the phase II part, the primary endpoint was 2-year overall survival (OS) rate, and secondary endpoints were the objective response rate, progression-free survival, OS, and safety profile. Results: In the phase I part, although maximum tolerated dose was not obtained, the RD was carboplatin (area under the time-concentration curve, 4) and nab-PTX (100 mg/m(2)). Of the evaluable 28 patients, the rate of 2-year OS was 67.8% (95% confidence interval, 49.3%-82.1%). The objective response rate was 96.4%, and the median follow-up time was 33.2 months. The median progression-free survival was 18.2 months (95% confidence interval, 13.1 months to not reached). The most common toxicities of grade 3 or higher were neutropenia (60.5%), anemia (14.2%), thromboc openia (7.2%), and pneumonitis (3.6%). Conclusions: This study achieved the primary endpoint. Biweekly carboplatin and nab-PTX with concurrent RT was well-tolerated and exerted promising antitumor activity. (C) 2020 The Author(s). Published by Elsevier Inc.