Phase II trial of bexarotene capsules in patients with advanced non-small-cell lung cancer after failure of two or more previous therapies

被引:115
作者
Govindan, Ramaswamy
Crowley, John
Schwartzberg, Lee
Kennedy, Peter
Williams, Charles
Ekstrand, Bradley
Sandler, Alan
Jaunakais, Dinah
Bolejack, Vanessa
Ghalie, Richard
机构
[1] Washington Univ, Sch Med, St Louis, MO 63110 USA
[2] Canc Res & Biostat, Seattle, WA USA
[3] W Clin, Memphis, TN USA
[4] Kenmar Res Inst, Los Angeles, CA USA
[5] Calif Canc Care, San Mateo, CA USA
[6] Ligand Pharmaceut Inc, San Diego, CA USA
[7] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA
[8] Vanderbilt Ingram Canc Ctr, Nashville, TN USA
关键词
D O I
10.1200/JCO.2006.07.7404
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Purpose To evaluate the effect of bexarotene on survival in patients with relapsed non-small-cell lung cancer (NSCLC). Patients and Methods Patients with stage IIIB NSCLC with pleural effusion or stage IV NSCLC, who had Eastern Cooperative Oncology Group performance status 0 to 2, and were previously treated with >= two different regimens that must have included a platinum and a taxane, received oral bexarotene 400 mg/m(2)/d plus concomitant levothyroxine and a lipid-lowering agent. Primary efficacy end point was survival. Results For the 146 assessable patients treated with bexarotene, median age was 66 years ( range, 34 to 87 years), 51% were men, and the median number of prior regimens was three ( range, one to seven). The overall median survival was 5 months (95% CI, 4 to 7 months) and the 1-year survival was 23% ( 95% CI, 16% to 31%). Survival was significantly longer in patients with bexarotene-induced hypertriglyceridemia and/or skin rash. In 26 patients who had both adverse effects, the median and 1-year survival rates were 12 months ( 95% CI, 8 to 15 months) and 48%, respectively. In 40 patients who had neither adverse effect, median and 1-year survival rates were 2 months ( 95% CI, 2 to 5 months) and 15%, respectively ( P =.0002). Twenty patients (14%) discontinued therapy because of bexarotene-related toxicity. For the remaining patients, adverse reactions to bexarotene were generally mild to moderate. Conclusion In the intent-to-treat population, bexarotene given as third or subsequent line of therapy for relapsed NSCLC did not achieve the intended median survival of 6 months. Survival may have been extended in patients who developed bexarotene-induced hypertriglyceremia and/or skin rash. It is important to confirm these observations in a randomized controlled trial.
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页码:4848 / 4854
页数:7
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