Abstract
LESSONS LEARNED: The concomitant use of weekly nab-paclitaxel and carboplatin with concurrent radiotherapy was demonstrated to be a safe therapeutic approach in this phase I trial of 10 evaluable patients with stage III NSCLC.Despite the lack of systemic glucocorticoids, there were no reported infusion reactions or cases of peripheral neuropathy in this trial, both of which are known to occur with the use of paclitaxel. BACKGROUND: Unresectable stage III non-small cell lung cancer (NSCLC) has a 5-year survival rate of 20%, and concurrent chemoradiotherapy results in significant toxicity with the use of current chemotherapeutic agents. nab-Paclitaxel was approved by the U.S. Food and Drug Administration in October 2012 for use along with carboplatin in advanced NSCLC. This study was undertaken to determine the maximum tolerated dose and dose-limiting toxicities (DLTs) of weekly nab-paclitaxel given in combination with carboplatin and concurrent radiotherapy in patients with unresectable stage III NSCLC. METHODS: Escalating doses of once-weekly nab-paclitaxel were given along with once-weekly carboplatin area under the plasma concentration time curve (AUC) of 2 and concurrent radiotherapy 66 Gy in 33 fractions, followed by 2 cycles of carboplatin and nab-paclitaxel consolidation chemotherapy. RESULTS: Eleven patients were enrolled and received treatment per protocol, with 10 evaluable for efficacy and toxicity. At dose level 1 (nab-paclitaxel 60 mg/m(2)), 2 DLTs were observed: esophagitis and radiation dermatitis. Six patients were enrolled at dose level 0 (nab-paclitaxel 40 mg/m(2)) with no DLTs. Nine of 10 evaluable patients had a partial response. CONCLUSION: Concurrent chemoradiotherapy with nab-paclitaxel 40 mg/m(2) and carboplatin AUC 2 is a safe and well-tolerated therapeutic regimen in patients with stage III NSCLC. A separate phase I/II study to evaluate the efficacy of this regimen is under way.