Phase I trial of nanoparticle albumin-bound paclitaxel in combination with gemcitabine in patients with thoracic malignancies

Background: Nab-paclitaxel has a different toxicity profile than solvent-based paclitaxel including a lower rate of severe neutropenia. This trial was designed to determine the maximum tolerated dose and dose limiting toxicities (DLT) of nab-paclitaxel in combination with gemcitabine. Methods: Patients were required to have a performance status of 0 to 1, <= three prior cytotoxic chemotherapy regimens, and preserved renal, hepatic, and bone marrow function. Patients received gemcitabine 1000 mg/m(2) on days 1, 8 in all cohorts, and nab-paclitaxel at doses of 260, 300, 340 mg/m(2) every 21 days depending on the treatment cohort (I cycle = 21 days). DLT were assessed after the first cycle, and doses were escalated in cohorts of 3 to 6 patients. Results: Eighteen patients were consented and 15 patients are evaluable [median age 62 years (range, 35-75); median number of prior treatments 3 (range, 1-4); tumor types: non-small cell lung cancer (NSCLC) (n = 8), small cell lung cancer (SCLC) (n = 6), and esophageal cancer (n = 1)]. At a nab-paclitaxel dose of 300 mg/m(2), 1 of 6 pts experienced a DLT (omission of day 8 gemcitabine due to absolute neutrophil count <500), and at an nab-paclitaxel dose of 340 mg/m(2) 2 of 3 patients experienced a DLT (1 pt grade 3 rash and pruritus; 1 pt grade 3 fatigue and anorexia). Responses were observed in NSCLC and SCLC. Conclusions: The maximum tolerated dose of nab-paclitaxel is 300 mg/m(2) in combination with gemcitabine 1000 mg/m(2) on days 1, 8 every 21 days. This combination demonstrated activity in previously treated NSCLC and SCLC patients.