A phase I study of nab-paclitaxel (nP) with carboplatin (C) and thoracic radiation (TRT) in patients with locally advanced NSCLC.

Abstract

7046 Background: One third of patients (pts) with NSCLC present with localized, unresectable disease. Concurrent chemoradiotherapy is well established with weekly paclitaxel and C with median survival of ~14 months. Nanoparticle albumin-bound (nab) paclitaxel (nP) is a cremophor-free formulation of paclitaxel designed to improve solubility and intra-tumor delivery. This phase I trial evaluates weekly nP + C + TRT in pts with unresectable stage III NSCLC. Methods: Pts with inoperable Stage IIIA or IIIB NSCLC, PS 0-1, and FEV 1 >800 ml entered escalating dose cohorts in a modified 3+3 design of nP weekly, beginning at 40 mg/m2 and increasing by 20 mg/m2 increments, in combination with C (AUC 2) weekly for 7 weeks and concurrent RT 66 Gy/33 fractions by either 3D conformal or intensity-modulated techniques. Pts received 2 cycles of consolidation therapy with full dose nP (100 mg/m2 weekly for 3 weeks) and C (AUC 6 on day one of each cycle) every 21d. The DLT period is defined as the concurrent chemoradiation period. Results: Eleven pts were enrolled. Ten pts were treated at 2 dose levels of nP, 40mg/m2 (6 pts) and 60mg/m2 (4 pts). One pt signed consent and then withdrew. Six pts were treated at 40mg/m2 with no DLT. Four pts were treated at 60mg/m2 with 2 DLT of radiation dermatitis and esophagitis. During concurrent treatment, Grade 2 toxicities were fatigue, dehydration, nausea, dysphagia, esophagitis, mucositis, hypoxia, neutropenia, anemia, and thrombocytopenia, and Grade 3 toxicities were neutropenia, mucositis, esophagitis, and dermatitis. No grade 4 toxicities were seen during concurrent treatment. Ten pts were evaluable for response with 9 PR and 1 SD. Seven patients have progressed 3, 5, 6, 7, and 8, 16 and 20 months after enrollment, and 3 patients remain stable at 2, 4, and 28 months. The recommended Phase II dose of weekly nP is 40mg/m2. Conclusions: Weekly nP is safe and well tolerated at 40mg/m2 when used in combination with weekly C (AUC2) and RT (66Gy) with AEs expected for concurrent chemoradiotherapy. A Phase II study to further evaluate this regimen is underway.