title: Phase II evaluation of docetaxel plus exisulind in patients with androgen independent prostate carcinoma.
abstract: OBJECTIVE
  In this phase II study, the combination of docetaxel and exisulind (a GMP phosphodiesterase inhibitor) was given to patients with metastatic androgen independent prostate cancer (AIPC) to establish efficacy, assess toxicity, and determine pharmacokinetics of docetaxel administered alone and in combination with exisulind.
  
  
  METHODS
  Fourteen patients with metastatic AIPC were registered to receive weekly docetaxel for 4 weeks, followed by 2 weeks of rest; repeated up to a maximum of 6 cycles. Exisulind 250 mg was given orally twice a day starting on day 8 of the study and taken continuously.
  
  
  RESULTS
  All patients were evaluable for toxicity, response and survival. Grade 3 reversible toxicities included: fatigue, nausea, diarrhea, abdominal pain, rash, syncope, pulmonary edema, deep vein thrombosis, congestive heart failure, and elevations in transaminases, requiring therapy delays and/or dose reductions, or removal from therapy. Only 3 out of 14 patients (21.4%) had a 50% decline in prostate specific antigen (PSA) level that lasted > or =4 weeks; 1 out of 14 patients (7%) had a lymph node response. Median survival was 17.28 months. Docetaxel pharmacokinetics for 11 patients demonstrated mean +/- SD clearance values that were similar during week 1 and week 3 when exisulind had been added.
  
  
  CONCLUSIONS
  : Overall, our trial indicated that the toxicity profile and efficacy of this regimen is unlikely to be substantially better than single agent docetaxel.
authors.affiliation: Prostate Cancer Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA. sinibvi@jhmi.edu
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Sinibaldi
authors.forename: Kathy
authors.initials: K
authors.lastname: Elza-Brown
authors.forename: Jill
authors.initials: J
authors.lastname: Schmidt
authors.forename: Mario A
authors.initials: MA
authors.lastname: Eisenberger
authors.forename: Eli
authors.initials: E
authors.lastname: Rosenbaum
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Denmeade
authors.forename: Roberto
authors.initials: R
authors.lastname: Pili
authors.forename: Janet
authors.initials: J
authors.lastname: Walczak
authors.forename: Sharyn D
authors.initials: SD
authors.lastname: Baker
authors.forename: Marianna
authors.initials: M
authors.lastname: Zahurak
authors.forename: Michael A
authors.initials: MA
authors.lastname: Carducci
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000077143:Docetaxel; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013467:Sulindac / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D043823:Taxoids; D000077143:Docetaxel; D013467:Sulindac; C025463:sulindac sulfone