title: Retrospective analysis of the consequences of acid suppressive therapy on ketoconazole efficacy in advanced castration-resistant prostate cancer.
abstract: BACKGROUND
  The area under the curve of a single ketoconazole dose has been shown to decrease significantly when administered with acid suppressive therapy. No published studies have examined the clinical impact of concurrent ketoconazole and acid suppressive therapy in patients with castration-resistant prostate cancer (CRPC).
  
  
  OBJECTIVE
  To evaluate the effect of acid suppressive therapy on prostate-specific antigen (PSA) response rate in CRPC patients receiving ketoconazole.
  
  
  METHODS
  This retrospective study evaluated CRPC patients treated with ketoconazole 3 times daily between January 1, 1999, and September 30, 2009. Patients included in the analysis had failed androgen deprivation therapy, and were subsequently initiated on ketoconazole. Response (PSA decline ≥50% maintained ≥4 weeks) was evaluated in patients receiving ketoconazole with (group 1 [G1]) or without (group 2 [G2]) concurrent acid suppressive therapy.
  
  
  RESULTS
  Thirty patients (G1: 11 patients; G2: 19 patients) were included in the analysis. Mean age in G1 and G2 was 71.8 and 69.6 years, respectively. Most patients had received prior therapy with an antiandrogen (90.9% G1; 100% G2) and fewer patients received antiandrogen withdrawal therapy (27.3% G1; 21.1% G2). Median baseline PSA was 109.4 (G1) and 86.9 ng/mL (G2) (p = 0.55). Median duration of ketoconazole was 7.2 months in G1 and 5.8 months in G2 (p = 0.09). Ketoconazole adherence was 82% (G1) and 100% (G2). Median duration of concurrent acid suppressive therapy was 3.8 months (range 2.0-20.4) in G1. PSA response (72.7% and 47.4%; p = 0.26) and time to PSA response (1.2 vs 0.9 mo; p = 0.53) were statistically similar between G1 and G2, respectively. Median progression free survival was higher in G1 (11.5 vs 6.9 months in G2; p = 0.047).
  
  
  CONCLUSIONS
  Use of concurrent acid suppressive therapy and ketoconazole in CRPC patients did not decrease PSA response rate, and progression free survival was unexpectedly higher compared with the non-acid suppressive therapy group. Larger studies are needed to verify the clinical impact of acid suppressive therapy in combination with ketoconazole.
authors.affiliation: Texas Tech University Health Sciences Center, Dallas, USA.
authors.forename: Sidney V
authors.initials: SV
authors.lastname: Keisner
authors.forename: Sachin R
authors.initials: SR
authors.lastname: Shah
authors.forename: Gary W
authors.initials: GW
authors.lastname: Jean
authors.forename: Sarah M Gressett
authors.initials: SM
authors.lastname: Ussery
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Dowell
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004347:Drug Interactions; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D005767:Gastrointestinal Diseases / Q000150:complications / Q000188:drug therapy; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D054328:Proton Pump Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D054328:Proton Pump Inhibitors; D017430:Prostate-Specific Antigen; D007654:Ketoconazole