title: Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: a randomized phase III trial.
abstract: BACKGROUND AE-941 is a standardized aqueous shark cartilage extract with antiangiogenic properties that has previously been evaluated in phase I and II clinical trials. Our objective was to determine the effect of adding AE-941 to chemoradiotherapy on overall survival of patients with unresectable stage III non-small cell lung cancer (NSCLC). METHODS A randomized, double-blinded, placebo-controlled, phase III clinical trial was designed to test the efficacy of AE-941 in unresectable stage III NSCLC patients who were treated with chemoradiotherapy. Between June 5, 2000, and February 6, 2006, 379 eligible patients were enrolled in community and academic oncology centers across the United States and Canada. In February 2006, the trial was closed to new patient entry before meeting the target sample size because of insufficient accrual. All subjects received induction chemotherapy followed by concurrent chemotherapy with chest radiotherapy. Each participating center administered one of the two chemotherapy regimens, either carboplatin and paclitaxel, or cisplatin and vinorelbine. The primary endpoint was overall survival, and secondary endpoints were time to progression, progression-free survival, tumor response rate, and toxic effects. Event-time distributions were estimated by the Kaplan-Meier method. All statistical tests were two-sided. RESULTS There was no statistically significant difference in overall survival between the chemoradiotherapy plus AE-941 group (n = 188; median survival = 14.4 months, 95% confidence interval = 12.6 to 17.9 months) and the chemoradiotherapy plus placebo group (n = 191; median survival = 15.6 months, 95% confidence interval = 13.8 to 18.1 months) (P = .73). Time to progression, progression-free survival, and tumor response rates were not statistically significantly different between the AE-941 and the placebo groups. No differences between the two groups were observed in common grade 3 or higher toxic effects attributable to chemoradiotherapy. CONCLUSIONS The addition of AE-941 to chemoradiotherapy did not improve overall survival in patients with unresectable stage III NSCLC. This study does not support the use of shark cartilage-derived products as therapy for lung cancer.
authors.affiliation: Department of Thoracic/Head & Neck Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd, Unit 432, Houston, TX 77030-4009, USA. clu@mdanderson.org
authors.forename: Charles
authors.initials: C
authors.lastname: Lu
authors.forename: J Jack
authors.initials: JJ
authors.lastname: Lee
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Komaki
authors.forename: Roy S
authors.initials: RS
authors.lastname: Herbst
authors.forename: Lei
authors.initials: L
authors.lastname: Feng
authors.forename: William K
authors.initials: WK
authors.lastname: Evans
authors.forename: Hak
authors.initials: H
authors.lastname: Choy
authors.forename: Pierre
authors.initials: P
authors.lastname: Desjardins
authors.forename: Benjamin T
authors.initials: BT
authors.lastname: Esparaz
authors.forename: Mylene T
authors.initials: MT
authors.lastname: Truong
authors.forename: Scott
authors.initials: S
authors.lastname: Saxman
authors.forename: Joseph
authors.initials: J
authors.lastname: Kelaghan
authors.forename: Archie
authors.initials: A
authors.lastname: Bleyer
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fisch
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001688:Biological Products / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002356:Cartilage; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D018714:Radiotherapy, Adjuvant; D014020:Tissue Extracts / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D001688:Biological Products; D014020:Tissue Extracts; C111481:shark cartilage extract