Author of

• 12592

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  P3.10 - Poster Session 3 - Chemotherapy (ID 210)

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

  • 12641

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    P3.10-049 - Combination Chemotherapy and autophagy Inhibition with Hydroxychloroquine for Advanced Non-small Cell Lung Cancer (ID 3151)

    09:30 - 09:30  |  Author(s): J. Mehnert
    • Abstract

    Background
    Autophagy (ATG) preserves tumor growth potential during cellular stresses, and may thus promote chemotherapy resistance. Hydroxychloroquine (HCQ) inhibits ATG in in-vitro and in-vivo models.

    Methods
    We thus initiated a phase II study of HCQ (200 mg/d p.o, twice daily) plus I.V. paclitaxel 200 mg/M2 and carboplatin AUC=6 every 21 days (group [GRP] 1) plus I.V. bevacizumab (GRP2; 15 mg/kg every. 21days as per Bev criteria).

    Results
    We entered 25 PS 0-1 patients (Pts), 14M/11F; 19 (5/4) in GRP1, 16 (9/7) GRP2. Median PS =1. Median age =70. Overall: 0 CRs; 13/25 (52%, 90% CI 40,64) Pts achieved PR (4/9 GRP1; 9/16 GRP2); 5/25 achieved SD (2/9 GRP1, 3/16 GRP2); 5/25 had PD, and 2/25 remain too early. Median F/U is 16 months, median TTP was 6+ months, and median OS was 10+ months. Pharmacokinetic analysis of CINJ phase I HCQ studies, showed results similar to studies in arthritis: HCQ was membrane bound at doses up to 800 mg/day, but free HCQ levels were seen at 1200 mg/day. In parallel laboratory studies, engineered murine k-ras -/- lung cancer models were dependent on ATG, and ATG inhibitors blocked tumor development and progression. K-ras data, available on 4/25 Pts showed 1/1 k-ras wt had PD. Among 3 Pts with k-ras-mutant tumors, 2 achieved PR and 1 SD

    Conclusion
    Further k-ras assessment on available tissue is in process. This study continues with HCQ at 1200 mg/day and required k-ras assessment.