title: Low dose of ketoconazole in patients with prostate adenocarcinoma resistant to pharmacological castration.
abstract: OBJECTIVE
  • To assess the efficacy of ketoconazole in patients with castration-resistant prostate cancer (CRPC).
  
  
  METHODS
  • From April 2008 to November 2009, 37 patients with CRPC have been treated with ketoconazole. The primary endpoint was the prostate-specific antigen (PSA) response; the secondary endpoints were progression-free survival and safety profile. • Ketoconazole was administered by oral route at a dose of 200 mg every 8 h continuous dosing until the onset of serious adverse events or disease progression. • The study was based on a two-step design with an interim efficacy analysis carried out on the first 12 patients accrued.
  
  
  RESULTS
  • Main characteristics of population were: median age 75 years (range 60-88); baseline mean PSA 28.8 ng/mL (4.3-1000); 30 patients previously challenged with at least two lines of hormone therapy; 15 patients previously treated with chemotherapy. • Biochemical responses accounted for: two complete responses (5%), six partial responses (16%), 13 patients with stable disease (35%), and 14 with progressive disease (38%). Of 15 patients resistant to chemotherapy, overall disease control (complete plus partial responses plus stable disease) was recorded in seven of them. • Treatment was feasible without inducing grade 3-4 adverse events. The most common grade 1-2 adverse events were asthenia (27%), vomiting (8%) and abdominal pain (8%).
  
  
  CONCLUSIONS
  • Treatment with low-dose ketoconazole is feasible and well tolerated. The efficacy was satisfactory in patients previously treated with chemotherapy.
authors.affiliation: Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori of Milan, Milan, Italy. giuseppe.procopio@istitutotumori.mi.it
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Procopio
authors.forename: Valentina
authors.initials: V
authors.lastname: Guadalupi
authors.forename: Maria Olga
authors.initials: MO
authors.lastname: Giganti
authors.forename: Luigi
authors.initials: L
authors.lastname: Mariani
authors.forename: Roberto
authors.initials: R
authors.lastname: Salvioni
authors.forename: Nicola
authors.initials: N
authors.lastname: Nicolai
authors.forename: Filippo
authors.initials: F
authors.lastname: Capone
authors.forename: Riccardo
authors.initials: R
authors.lastname: Valdagni
authors.forename: Emilio
authors.initials: E
authors.lastname: Bajetta
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D000728:Androgens / Q000378:metabolism; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects / Q000627:therapeutic use*; D004812:Epidemiologic Methods; D006801:Humans; D007654:Ketoconazole / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; D017430:Prostate-Specific Antigen; D007654:Ketoconazole