title: Intensive anti-inflammatory therapy with dexamethasone in patients with non-small cell lung cancer: effect on chemotherapy toxicity and efficacy.
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/m(2) 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.
authors.affiliation: Department of Pharmaceutical Sciences, The College of Pharmacy, University of Kentucky, Lexington, KY, USA.
authors.forename: Markos
authors.initials: M
authors.lastname: Leggas
authors.forename: Kuei-Ling
authors.initials: KL
authors.lastname: Kuo
authors.forename: Francisco
authors.initials: F
authors.lastname: Robert
authors.forename: Gretchen
authors.initials: G
authors.lastname: Cloud
authors.forename: Mollie
authors.initials: M
authors.lastname: deShazo
authors.forename: Ruiwen
authors.initials: R
authors.lastname: Zhang
authors.forename: Mao
authors.initials: M
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Steve
authors.initials: S
authors.lastname: Davidson
authors.forename: John
authors.initials: J
authors.lastname: Rinehart
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000556:secondary; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D003907:Dexamethasone / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D014018:Tissue Distribution; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D005938:Glucocorticoids; D003841:Deoxycytidine; D003907:Dexamethasone; D016190:Carboplatin; D000093542:Gemcitabine