Phase II trial of the novel retinoid, bexarotene, and gemcitabine plus carboplatin in advanced non-small-cell lung cancer.

PURPOSE: Platinum-based chemotherapy is the standard treatment for advanced non-small-cell lung cancer (NSCLC). Unfortunately, a plateau in efficacy with currently available agents has been reached. Previous studies of the retinoid, bexarotene, a retinoid X receptor-specific ligand, have indicated that it may improve outcome in advanced NSCLC. PATIENTS AND METHODS: Patients with previously untreated stage IIIB or stage IV disease, a performance status of 0 to 2, and adequate organ status were entered. Treatment consisted of up to six cycles of carboplatin (area under the curve = 5.0 on day 1) and gemcitabine (1,000 mg/m2 on days 1 and 8) administered every 21 days. Bexarotene 400 mg/m2 orally was to be administered continuously beginning on day 1 and until progression of disease. All patients received atorvastatin 10 mg orally beginning before bexarotene. The objective was to demonstrate a 1-year survival rate of more than 50%.
RESULTS: Forty-eight patients were entered; all were assessable for survival, and 47 were assessable for toxicity and response. The therapeutic regimen was well tolerated except for hypertriglyceridemia. The median time to progression was 6.7 months, and overall median survival was 12.7 months. There was a 25% response rate and a 1-year survival rate of 53%. These results were compared with the outcome of 33 patients treated at our institution with two-drug, platinum-based chemotherapy on controlled trials with similar entry criteria in the previous 5 years.
CONCLUSION: Bexarotene can be safely added to platinum-based chemotherapy provided that there is aggressive prophylaxis of hypertriglyceridemia. The median time to progression and overall survival are promising and warrant further evaluation of bexarotene in advanced NSCLC.