A dose finding study of weekly and every-3-week nab-Paclitaxel followed by carboplatin as first-line therapy in patients with advanced non-small cell lung cancer

• Published in: Journal of thoracic oncology Vol. 5; no. 6; p. 852
• Main Authors: Socinski, Mark A, Manikhas, Georgiy M, Stroyakovsky, Daniil L, Makhson, Anatoly N, Cheporov, Sergey V, Orlov, Sergei V, Yablonsky, Petr K, Bhar, Paul, Iglesias, Jose
• Format: Journal Article
• Language: English
• Published: United States 01-06-2010
• Subjects: Adult; Aged; Aged, 80 and over; Albumin-Bound Paclitaxel; Albumins - administration & dosage; Albumins - adverse effects; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Carboplatin - administration & dosage; Carboplatin - adverse effects; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Drug Administration Schedule; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Middle Aged; Paclitaxel - administration & dosage; Paclitaxel - adverse effects; Retrospective Studies
• ISSN: 1556-1380
• DOI: 10.1097/JTO.0b013e3181d5e39e

This nonrandomized study aimed to identify the optimal dose of every-3-week (q3w) and weekly nab-paclitaxel plus q3w carboplatin as first-line therapy in patients with advanced non-small cell lung cancer (NSCLC) for a phase 3 trial.
Previously untreated patients with advanced NSCLC enrolled sequentially into seven cohorts (25 patients/cohort, N = 175). Cohorts 1 to 4 and 5 to 7 received nab-paclitaxel q3w and weekly, respectively. Patients were evaluated for efficacy and safety.
The most common treatment-related > or = grade 3 adverse events were neutropenia (60%), neuropathy (19%), fatigue (9%), and thrombocytopenia (29%) (no grade 4 neuropathy or fatigue). A 100 mg/m(2) weekly nab-paclitaxel produced less serious adverse events than other doses/schedules. Response rate (RR) was greater in the weekly versus q3w cohorts (47% vs. 30%). Median progression-free survival (PFS) ranged from 4.8 to 6.9 months, and overall survival (OS) ranged from 8.3 to 15.0 months (all cohorts). Patients receiving 100 mg/m(2) weekly nab-paclitaxel achieved 48% RR with 6.2 and 11.3 months of PFS and OS, respectively. In a retrospective analysis, patients with nonsquamous cell carcinoma receiving weekly nab-paclitaxel had significantly improved RR (59.4% vs. 23.5%, respectively, p = 0.003), and >2 months longer PFS and OS compared with q3w schedule. In patients with squamous cell carcinoma, the q3w schedule significantly increased PFS by 3 months (p = 0.014) and OS by >2 months (no difference in RR) compared with the weekly schedule.
nab-Paclitaxel plus carboplatin is an effective therapy for advanced NSCLC. Based on favorable efficacy and safety profiles, a phase 3, randomized, multicenter study comparing 100 mg/m(2) weekly nab-paclitaxel plus q3w carboplatin to solvent-based paclitaxel plus carboplatin has enrolled patients.