Phase II trial of bexarotene capsules in patients with advanced non-small-cell lung cancer after failure of two or more previous therapies.
OBJECTIVE
To evaluate the effect of bexarotene on survival in patients with relapsed non-small-cell lung cancer (NSCLC).


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 > or = two different regimens that must have included a platinum and a taxane, received oral bexarotene 400 mg/m2/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.


CONCLUSIONS
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.
Govindan
Ramaswamy
R
Washington University School of Medicine, St Louis, MO 63110, USA. rgovinda@im.wustl.edu
Crowley
John
J
Schwartzberg
Lee
L
Kennedy
Peter
P
Williams
Charles
C
Ekstrand
Bradley
B
Sandler
Alan
A
Jaunakais
Dinah
D
Bolejack
Vanessa
V
Ghalie
Richard
R
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016588:Anticarcinogenic Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D000077610:Bexarotene; D002214:Capsules; D002289:Carcinoma, Non-Small-Cell Lung / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010996:Pleural Effusion / Q000209:etiology; D016019:Survival Analysis; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage* / Q000009:adverse effects*
D016588:Anticarcinogenic Agents; D002214:Capsules; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene