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

• Published in: Lung cancer (Amsterdam, Netherlands) Netherlands), 2010-03, Vol.67 (3), p.330-338
• Main Authors: Pandya, Kishan J, Gajra, Ajeet, Warsi, Ghulam M, Argonza-Aviles, Eliza, Ericson, Solveig G, Wozniak, Antoinette J
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antitumor activity; Biological and medical sciences; Bisphosphonate; Bone metastases; Bones, joints and connective tissue. Antiinflammatory agents; Canada; Carboplatin - administration & dosage; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Chemotherapy; Diphosphonates - administration & dosage; Diseases of the osteoarticular system; Female; Hematology, Oncology and Palliative Medicine; Humans; Imidazoles - administration & dosage; Lung cancer; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Male; Medical sciences; Middle Aged; Neoplasm; Neoplasm Staging; Pharmacology. Drug treatments; Pneumology; Pulmonary/Respiratory; Taxoids - administration & dosage; Tumors; Tumors of striated muscle and skeleton; Tumors of the respiratory system and mediastinum; United States; Zoledronic acid
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2009.04.020

Abstract 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/m2 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 266 d vs 206 d ( P = .4855) and 64.1% 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.