title: 13-cis retinoic acid and complete androgen blockade in advanced hormone-naive prostate cancer patients: report of a phase II randomized study.
abstract: OBJECTIVE
  13 cis Retinoic acid (isotretinoin) is a retinoid with preclinical evidence of anti-prostate cancer activity. This phase II, cross-over, randomized study of advanced, predominantly androgen-dependent prostate cancer patients was designed to assess primarily the effect on prostate-specific antigen (PSA) decline and toxicity of adding isotretinoin to hormonal therapy and, secondarily, the potential antitumor activity of the combination.
  
  
  METHODS
  Thirty-seven D0 to D2 patients were randomized soon after initiating luteinizing hormone-releasing hormone agonist with antiandrogen treatment to add (arm 1) or not (arm 2) isotretinoin from weeks 1 to 12. After cross-over on week 13, patients in arm 1 discontinued while patients in arm 2 added isotretinoin from weeks 14 to 25. Observation on hormonal therapy alone continued until week 49.
  
  
  RESULTS
  Baseline and randomization median PSA for 30 assessable patients were, respectively, 34 and 18.2 ng/mL for arm 1 and 31 and 13.4 ng/mL for arm 2. Median PSA at week 13 was 0.5 ng/mL (range, < 0.05 to 136 ng/mL) for arm 1 and 0.7 ng/mL (range, < 0.05 to 4.4 ng/mL) for arm 2; at week 25, 0.1 ng/mL (range, < 0.05 to 121 ng/mL) and 0.4 ng/mL (range, < 0.05 to 3.1 ng/mL), respectively. At week 49, arm 1 had median PSA of 0.1 ng/mL (range, < 0.05 to 345 ng/mL) and arm 2, 0.3 ng/mL (range, < 0.05 to 8.8 ng/mL); seven of 15 and three of 15 patients, respectively, had undetectable PSA levels (P =.12). Frequent isotretinoin-related toxicity included grade 1 cheilitis (76%), skin dryness (43%), and elevated triglycerides (50%).
  
  
  CONCLUSIONS
  Isotretinoin does not impair PSA decline or add significant toxicity to hormonal therapy. An adequately powered, randomized study would be required to determine whether the combination is superior to standard hormonal treatment.
authors.affiliation: Division of Medical Oncology and Department of Urology, Mount Sinai School of Medicine, New York, NY 10029, USA. anna.ferrari@mssm.edu
authors.forename: Anna C
authors.initials: AC
authors.lastname: Ferrari
authors.forename: Nelson
authors.initials: N
authors.lastname: Stone
authors.forename: Richard
authors.initials: R
authors.lastname: Stock
authors.forename: Myron
authors.initials: M
authors.lastname: Bednar
authors.forename: Isaac
authors.initials: I
authors.lastname: Esseesse
authors.forename: Harvinder
authors.initials: H
authors.lastname: Singh
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Baldwin
authors.forename: John
authors.initials: J
authors.lastname: Mandeli
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000726:Androgen Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D018592:Cross-Over Studies; D006801:Humans; D007279:Injections, Subcutaneous; D015474:Isotretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012871:Skin Diseases / Q000139:chemically induced; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D000726:Androgen Antagonists; D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D014280:Triglycerides; D017430:Prostate-Specific Antigen; D015474:Isotretinoin