Intensive anti-inflammatory therapy with dexamethasone in patients with non-small cell lung cancer: Effect on chemotherapy toxicity and efficacy

Academic Article

Abstract

  • Background: Our preclinical and clinical data suggest that pretreatment with dexamethasone 4 days prior to chemotherapy increased the efficacy and decreased the toxicity of carboplatin and gemcitabine. To translate these findings to patients, we have undertaken a Phase 1/2 clinical trial. Methods: Thirty patients with advanced non-small cell lung cancer (NSCLC) received gemcitabine, 1,000 mg/m2 on days 1 and 8, and carboplatin, AUC 5.5 on day 1. Patients were randomized (1:2:2) to receive, no dexamethasone (cohort 1), or oral dexamethasone at 8 mg (cohort 2) or 16 mg (cohort 3) twice per day, 4 days before and of the day of chemotherapy. Dexamethasone was administered to patients in cohorts 2 and 3 during courses 2-4. Results: In cohorts 1, 2, and 3, patients completing four planned courses of therapy were: 1/6, 6/12, 9/12. Partial responses (RECIST) were: 2/6, 6/12, and 7/12. Overall, dexamethasone significantly improved AGC and platelet nadirs and recovery times. There were no significant differences in non-hematologic toxicities between cohorts and no significant differences in pharmacokinetic parameters between course 1 and 2 in any cohort. Conclusions: These data support our previous preclinical and clinical observations that dexamethasone pre-treatment decreases hematopoietic toxicity and improves efficacy of this chemotherapeutic regimen in patients with metastatic non-small cell lung cancer and suggests that further randomized trials should be undertaken. © 2008 Springer-Verlag.
  • Digital Object Identifier (doi)

    Author List

  • Leggas M; Kuo KL; Robert F; Cloud G; DeShazo M; Zhang R; Li M; Wang H; Davidson S; Rinehart J
  • Start Page

  • 731
  • End Page

  • 743
  • Volume

  • 63
  • Issue

  • 4