Weekly paclitaxel, carboplatin, and bexarotene for the treatment of patients with advanced non-small cell lung cancer: Efficacy results from a phase I/II study

Abstract

7243 Background: The combination of weekly paclitaxel (Taxol) and every 4 week carboplatin (Paraplatin) as first-line therapy for advanced non-small cell lung cancer (NSCLC) has been reported. The study noted a median survival time of 8.8 months and a 1-year survival of 39.5%. The current phase I/II study was designed to evaluate the tolerability and activity of the rexinoid, bexarotene (targretin) in combination with weekly paclitaxel and every 4 week carboplatin. Methods: Patients with confirmed stage IIIB or IV NSCLC and adequate organ function were enrolled. Prior chemotherapy was allowed for the phase I portion of this study. All patients were scheduled to receive paclitaxel 100 mg/m2 weekly for 3 doses every 4 weeks and carboplatin AUC = 6 monthly. Bexarotene oral capsules were administered daily starting on initial day of chemotherapy. Two dose levels of bexarotene were evaluated (300 mg/m2/day and 400 mg/m2/day). The recommended phase II dose of bexarotene was 400 mg/m2/day. Results: As of December 2004, 33 patients were enrolled, 13 patients receiving 300 mg/m2/day and 20 patients at 400 mg/m2/day of bexarotene. Patient characteristics include: age (median 59), gender (female 43%), stage (93% stage IV), Karnofsky performance status (37% with KPS 60–70%), prior chemotherapy (30%), prior radiation (33%), and prior surgery (33%). Hematologic toxicity was mild with grade 3 anemia in 3 pts and grade 3 neutropenia in 4 pts. Non-hematologic toxcities consisted primarily of hyperlipidemia and hypothyroidism which were medically managed. No cases of pancreatitis were observed. With a median follow-up of 15.1 months, the median survival time for all patients is 6.9 months with 1-year survival of 43%. The median survival time for chemotherapy-naive patients (n = 24) is 8.3 months with a 1-year survival of 47%. Conclusions: The 1-yr survival for chemotherapy-naive patients treated with bexarotene in combination with weekly paclitaxel and every 4 week carboplatin is encouraging. Ongoing phase III trials will determine whether adding bexarotene to conventional chemotherapy improves survival as a first line treatment for NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Bristol-Myers Squibb, Ligand Bristol-Myers Squibb, Ligand Bristol-Myers Squibb, Ligand