title: 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.
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 75mg/m(2) and carboplatin area under the concentration time curve 6 with (Arm A) or without (Arm B) zoledronic acid 4mg 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 (132d vs 132d; P=.9622). One-year OS times and best overall response rates were 266d vs 206d (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.
authors.affiliation: University of Rochester Medical Center, , Rochester, NY 14642, USA.
authors.forename: Kishan J
authors.initials: KJ
authors.lastname: Pandya
authors.forename: Ajeet
authors.initials: A
authors.lastname: Gajra
authors.forename: Ghulam M
authors.initials: GM
authors.lastname: Warsi
authors.forename: Eliza
authors.initials: E
authors.lastname: Argonza-Aviles
authors.forename: Solveig G
authors.initials: SG
authors.lastname: Ericson
authors.forename: Antoinette J
authors.initials: AJ
authors.lastname: Wozniak
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002170:Canada; D016190:Carboplatin / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D004164:Diphosphonates / Q000008:administration & dosage*; D000077143:Docetaxel; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D043823:Taxoids / Q000008:administration & dosage*; D014481:United States; D000077211:Zoledronic Acid
chemical_list: D004164:Diphosphonates; D007093:Imidazoles; D043823:Taxoids; D000077143:Docetaxel; D000077211:Zoledronic Acid; D016190:Carboplatin