Phase I/II study of bexarotene in combination with weekly paclitaxel and monthly carboplatin for the treatment of patients (pts) with advanced non-small cell lung cancer (NSCLC)

Abstract

7356 Background: This trial was based on a multicenter randomized phase II trial in advanced NSCLC where weekly paclitaxel and monthly carboplatin demonstrated favorable results. This trial was designed to combine this chemotherapy regimen with bexarotene, a retinoid that binds selectively to the nuclear receptor RXR now in phase III development. Methods: Pt eligibility: pathologic stage: IIIB/IV or recurrent metastatic disease, adequate hematological, hepatic, thyroid, lipid and renal function. Prior chemotherapy was allowed. Bexarotene oral capsules are administered daily starting on initial day of chemotherapy. Two dose levels of bexarotene were evaluated (300 mg/m2/day and 400 mg/m2/day). All patients were scheduled to receive paclitaxel 100 mg/m2 weekly for 3 doses every 4 weeks and carboplatin AUC = 6 monthly. Results: As of December 2003, 21 pts were enrolled, 8 receiving 300mg/m2/day and 13 at 400 mg/m2/day of bexarotene. Pt characteristics include: age (median 58), gender (female 43%), stage (86% stage IV), 24% Karnofsky performance status 60–70%, 29% prior chemotherapy, 33% prior radiation, 48% prior surgery. At the 300 mg/m2/day bexarotene dose level, 52% of the pts required a dose reduction in paclitaxel . At the 400 mg/m2/day dose level of bexarotene, 34% of the pts acquired a dose reduction in paclitaxel. Dose modification rates were higher in our study (52%/34%) than in the prior randomized study without bexarotene (14%). The primary serious adverse events (grade 3 or 4) were neutropenia (19%), hypertriglyceridemia (14%) and anemia (10%). Conclusions: Daily administration of bexarotene at 400 mg/m2/day in combination with weekly paclitaxel and monthly carboplatin is safe and feasible. Enrollment of chemotherapy naïve pts into the phase II portion of this trial continues. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Ligand Ligand Ligand; Genentech; Abbott; Amgen; Aventis; Bristol-Myers Squibb; GlaxoSmithKline; Ortho Biotech; Merck; Pfizer; OSI; Roche