Author of

• 11692

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  P2.10 - Poster Session 2 - Chemotherapy (ID 207)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11738

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    P2.10-046 - A phase I/II study of bexarotene with weekly paclitaxel and carboplatin for the treatment of patients with advanced non-small cell lung cancer (ID 2863)

    09:30 - 09:30  |  Author(s): S.K. Fink
    • Abstract

    Background
    The combination of weekly paclitaxel and every 4 week carboplatin as first-line therapy for advanced non-small cell lung cancer (NSCLC) has been report to result in a median survival time of 8.8 months and a 1-year survival of 39.5%. Retinoids and rexinoids are derivatives of vitamin A with anti-proliferative and differentiation inducing activity in a variety of cancer types, including NSCLC. Preclinical and early clinical work has shown promising results when rexinoids are combined with chemotherapy or targeted agents. We designed a phase I/II study to evaluate the tolerability and activity of the rexinoid, bexarotene in combination with weekly paclitaxel and every 4 week carboplatin to allow for closer interaction between the agents.

    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/m[2] 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/m[2]/day and 400 mg/m[2]/day). The recommended phase II dose of bexarotene was 400 mg/m[2]/day.

    Results
    33 patients (pts) were enrolled, 14 pts received 300 mg/m[2]/day and 19 pts received 400 mg/m[2]/day of bexarotene. Patient characteristics: age (median 59), gender (female 39%), stage (85% stage IV), Karnofsky performance status (KPS) (37% with KPS 60-70%), prior chemotherapy (30%), prior radiation (33%), and prior surgery (33%). Hematologic toxicity was mild with grade 3 anemia in 5 pts and grade 3 neutropenia in 7 pts. Non-hematologic toxicities consisted primarily of hyperlipidemia and hypothyroidism which were medically managed. No cases of pancreatitis were observed. With a median follow-up of nearly 9 years, the median survival time (MST) for all pts was 8.5 months with 1-year survival of 43%. MST for the 300mg dose was 6.5 months while the MST for the 400mg dose was 10.2 months. The median survival time for chemotherapy-naive pts (n = 24) was 8.3 months with a 1-year survival of 47%. There was no statistically significant difference in survival between those pts with or without dose modifications for side effects. MST was 8.4 months for the subset of pts who experienced hypertriglyceridemia compared to 4.9 months for the pts who did not develop hypertriglyceridemia.

    Conclusion
    The 43% 1-yr survival for chemotherapy-naive pts treated with bexarotene in combination with weekly paclitaxel and every 4 week carboplatin is encouraging. However, two reported phase III trials found no benefit from adding bexarotene to conventional chemotherapy. Our study dose confirmed the subgroup analysis for a significant positive correlation between bexarotene-induced hypertriglyceridemia and survival. Thus, our study which utilizes a different chemotherapy should be confirmed in future trials. Further research on biomarkers to identify subsets of patients that may benefit from bexarotene is warranted.