title: A phase II study of temozolomide in hormone-refractory prostate cancer.
abstract: BACKGROUND
  Hormone-refractory disseminated prostate cancer is a major oncological problem. Preclinical studies with temozolomide, an oral alkylating agent, in prostate cancer have shown encouraging results. In phase I studies the safety of temozolomide in non-prostate cancer patients has been demonstrated. Based on these results, a phase II study of temozolomide in patients with metastatic disease who had developed progressive symptomatic disease while on antiandrogen therapy, was initiated.
  
  
  METHODS
  A group of 18 patients started a 5-day temozolomide regimen, with a 28-day treatment cycle. Response parameters (prostate-specific antigen, bone scan, quality of life questionnaire) and toxicity (common toxicity criteria for international studies) were recorded at regular intervals.
  
  
  RESULTS
  Of the 18 patients, 16 were evaluable by completing two or three cycles. All patients developed progressive disease within two cycles, except one who had progressive disease at the end of cycle 3. Of the 16 evaluable patients, 11 developed new bone metastases (bone scan), 1 developed lung metastases, 4 had progressive disease as reflected by a 25% increase in serum PSA together with subjective progression, and 7 and 5 had progressive disease as reflected by decreased quality of life and increased pain score, respectively. Toxicity was limited to nausea and vomiting, which was effectively treated with antiemetic medication, and anemia and thrombocytopenia, which returned to normal values within 1 week.
  
  
  CONCLUSIONS
  Treatment with temozolomide was generally well tolerated, with occasionally moderate toxicity. As all patients developed progressive disease the results are rather discouraging. Temozolomide is ineffective for the treatment of patients with symptomatic progressive hormone-refractory prostate cancer.
authors.affiliation: Department of Urology, Erasmus University and Academic Hospital Rotterdam, The Netherlands.
authors.forename: J P
authors.initials: JP
authors.lastname: van Brussel
authors.forename: M B
authors.initials: MB
authors.lastname: Busstra
authors.forename: M S
authors.initials: MS
authors.lastname: Lang
authors.forename: T
authors.initials: T
authors.lastname: Catsburg
authors.forename: F H
authors.initials: FH
authors.lastname: Schröder
authors.forename: G H
authors.initials: GH
authors.lastname: Mickisch
mesh_terms: D000328:Adult; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D017430:Prostate-Specific Antigen; D000077204:Temozolomide