Multicenter, randomized, phase 2 study of zoledronic acid in combination with docetaxel and carboplatin in patients with unresectable stage IIIB or stage IV non-small cell lung cancer

This study was designed to evaluate the efficacy and safety of combined zoledronic acid and docetaxel/carboplatin in patients with non-small cell lung cancer (NSCLC) as preclinical studies showed synergistic antitumoral activity with bisphosphonates and docetaxel Patients with inoperable stage IIIB or stage IV NSCLC were randomized 2 1 to receive docetaxel 75 mg/m(2) and carboplatin area under the concentration time curve 6 with (Arm A) or without (Arm B) zoledronic acid 4 mg every 3 weeks for 6 cycles Patients responding in Arm A were rerandomized to receive monthly zoledronic acid (maximum. 12 months [Arm A1] or no zoledronic acid [Arm A2]) Patients responding in Arm B entered Arm B1 for follow-up evaluation only The primary endpoint was the proportion of patients without disease progression; secondary endpoints were time to disease progression (TTP), TTP in bone, best overall response rate, 1-year overall survival (OS) time, and safety; study not powered to detect endpoint differences. Of 150 patients, 98 were randomized to Arm A and 52 to Arm B. In the treatment phase, results were similar between groups in the proportion of patients without disease progression (40 9% vs 38 8%; P= 8096) and median TTP (132 d vs 132 d; P= 9622) One-year OS times and best overall response rates were 266d vs 206d (P=.4855) and 641% vs 72% (P= 3423), respectively, the study was not powered to detect differences In the follow-up phase, TTP and OS time were similar Adding zoledronic acid to docetaxel/carboplatin in advanced stage NSCLC patients was well tolerated, but provided little to no effect on disease progression endpoints (C) 2009 Elsevier Ireland Ltd All rights reserved.