PURPOSE: The purpose of this study was to determine whether addition of the synthetic rexinoid bexarotene (Targretin; Eisai Inc, Woodcliff Lake, NJ) to standard first-line carboplatin and paclitaxel therapy provides additional survival benefit in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIB disease with pleural effusion, or stage IV NSCLC and Eastern Cooperative Oncology Group performance status 0 to 1, were randomly assigned to bexarotene 400 mg/m(2)/d combined with carboplatin and paclitaxel, or assigned to carboplatin and paclitaxel alone. Bexarotene patients also received lipid-lowering agents on or before day 1. The primary efficacy end point was overall survival; secondary efficacy and supportive analyses were also conducted. RESULTS: A total of 612 patients (306 per arm) were enrolled onto the study. In the intent-to-treat population, no significant difference in survival occurred between the two arms. However, a subpopulation (approximately 40%) of bexarotene-treated patients who experienced National Cancer Institute grade 3/4 hypertriglyceridemia had significantly longer median survival than control patients (12.4 v 9.2 months; log-rank, P = .014). Bexarotene-treated patients with grade 3/4 hypertriglyceridemia who received the most benefit included those who were male, were smokers, experienced 6-month prior weight loss >or= 5%, and had stage IV disease. The incidence and severity of most adverse events were similar between arms, although hyperlipidemia, neutropenia, fatigue, leukopenia, arthralgia, and diarrhea were more frequent in the bexarotene arm. CONCLUSION: Although the addition of bexarotene to chemotherapy did not improve survival in the overall study population, occurrence of high-grade hypertriglyceridemia in bexarotene-treated patients strongly correlated with increased survival, suggesting that bexarotene may benefit a segment of first-line NSCLC patients.
RCT Entities:
PURPOSE: The purpose of this study was to determine whether addition of the synthetic rexinoidbexarotene (Targretin; Eisai Inc, Woodcliff Lake, NJ) to standard first-line carboplatin and paclitaxel therapy provides additional survival benefit in patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIB disease with pleural effusion, or stage IV NSCLC and Eastern Cooperative Oncology Group performance status 0 to 1, were randomly assigned to bexarotene 400 mg/m(2)/d combined with carboplatin and paclitaxel, or assigned to carboplatin and paclitaxel alone. Bexarotenepatients also received lipid-lowering agents on or before day 1. The primary efficacy end point was overall survival; secondary efficacy and supportive analyses were also conducted. RESULTS: A total of 612 patients (306 per arm) were enrolled onto the study. In the intent-to-treat population, no significant difference in survival occurred between the two arms. However, a subpopulation (approximately 40%) of bexarotene-treated patients who experienced National Cancer Institute grade 3/4 hypertriglyceridemia had significantly longer median survival than control patients (12.4 v 9.2 months; log-rank, P = .014). Bexarotene-treated patients with grade 3/4 hypertriglyceridemia who received the most benefit included those who were male, were smokers, experienced 6-month prior weight loss >or= 5%, and had stage IV disease. The incidence and severity of most adverse events were similar between arms, although hyperlipidemia, neutropenia, fatigue, leukopenia, arthralgia, and diarrhea were more frequent in the bexarotene arm. CONCLUSION: Although the addition of bexarotene to chemotherapy did not improve survival in the overall study population, occurrence of high-grade hypertriglyceridemia in bexarotene-treated patients strongly correlated with increased survival, suggesting that bexarotene may benefit a segment of first-line NSCLCpatients.
Authors: Konstantin H Dragnev; Tian Ma; Jobin Cyrus; Fabrizio Galimberti; Vincent Memoli; Alexander M Busch; Gregory J Tsongalis; Marc Seltzer; David Johnstone; Cherie P Erkmen; William Nugent; James R Rigas; Xi Liu; Sarah J Freemantle; Jonathan M Kurie; Samuel Waxman; Ethan Dmitrovsky Journal: Cancer Prev Res (Phila) Date: 2011-06
Authors: Marcia I Dawson; Mao Ye; Xihua Cao; Lulu Farhana; Qiong-Ying Hu; Yong Zhao; Li Ping Xu; Alice Kiselyuk; Ricardo G Correa; Li Yang; Tingjun Hou; John C Reed; Pamela Itkin-Ansari; Fred Levine; Michel F Sanner; Joseph A Fontana; Xiao-Kun Zhang Journal: ChemMedChem Date: 2009-07 Impact factor: 3.466
Authors: Ainhoa Mielgo; Vicente A Torres; Michael C Schmid; Ryon Graf; Samantha G Zeitlin; Pedro Lee; David J Shields; Simone Barbero; Colin Jamora; Dwayne G Stupack Journal: PLoS One Date: 2009-11-18 Impact factor: 3.240