title: A phase II trial evaluating the efficacy and safety of efavirenz in metastatic castration-resistant prostate cancer.
abstract: BACKGROUND
  Preclinical studies demonstrated that non-nucleoside reverse transcriptase inhibitors used for the treatment of HIV could antagonize tumor development. This led us to assess the efficacy of efavirenz in patients with metastatic castration-resistant prostate cancer (mCRPC) in a multicenter phase II study.
  
  
  METHODS
  We used a Simon two-stage design and a 3-month prostate-specific antigen (PSA) nonprogression rate of 40% as a primary objective. Patients received 600 mg efavirenz daily with the possibility of a dose increase in case of PSA progression. Exploratory analyses included pharmacokinetics of efavirenz plasma concentrations and correlations with clinical outcomes.
  
  
  RESULTS
  Among 53 assessable patients, we observed 15 instances of PSA nonprogression at 3 months, corresponding to a nonprogression rate of 28.3% (95% confidence interval: 16.8%-42.3%). The exploratory analysis revealed that for the 7 patients in whom optimal plasma concentration of efavirenz was achieved, PSA progression was observed in only 28.6% compared with 81.8% of patients with suboptimal plasma concentrations of efavirenz.
  
  
  CONCLUSIONS
  Although 600 mg efavirenz did not statistically improve the PSA nonprogression rate, our exploratory analysis suggests that higher plasma concentrations of this drug (i.e., use of increased dosages) may be of potential benefit for the treatment of mCRPC.
authors.affiliation: Department of Medical Oncology, Nimes University Hospital, Nimes, France; nadine.houede@chu-nimes.fr.
authors.forename: Nadine
authors.initials: N
authors.lastname: Houédé
authors.affiliation: Clinical Research and Clinical Epidemiology Unit, Bergonié Cancer Institute, Bordeaux, France;
authors.forename: Marina
authors.initials: M
authors.lastname: Pulido
authors.affiliation: Department of Oncology, Claudius Régaud Cancer Center, Toulouse, France;
authors.forename: Loic
authors.initials: L
authors.lastname: Mourey
authors.affiliation: Department of Medical Oncology, François Baclesse Cancer Center, Caen, France;
authors.forename: Florence
authors.initials: F
authors.lastname: Joly
authors.affiliation: Department of Medical Oncology, Antoine Lacassagne Cancer Center, Nice, France;
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Ferrero
authors.affiliation: Clinical Research and Clinical Epidemiology Unit, Bergonié Cancer Institute, Bordeaux, France;
authors.forename: Carine
authors.initials: C
authors.lastname: Bellera
authors.affiliation: Department of Medical Oncology, CHD La Roche sur Yon, La Roche sur Yon, France;
authors.forename: Frank
authors.initials: F
authors.lastname: Priou
authors.affiliation: Clinical Research and Clinical Epidemiology Unit, Bergonié Cancer Institute, Bordeaux, France;
authors.forename: Caroline
authors.initials: C
authors.lastname: Lalet
authors.affiliation: Alienor Farma, Parc Scientifique Unitec 1, Pessac, France;
authors.forename: Audrey
authors.initials: A
authors.lastname: Laroche-Clary
authors.affiliation: Centre Hospitalier de Pellegrin, Laboratoire de Pharmacologie et Toxicologie, Bordeaux, France;
authors.forename: Mireille Canal
authors.initials: MC
authors.lastname: Raffin
authors.affiliation: Alienor Farma, Parc Scientifique Unitec 1, Pessac, France;
authors.forename: François
authors.initials: F
authors.lastname: Ichas
authors.affiliation: Alienor Farma, Parc Scientifique Unitec 1, Pessac, France;
authors.forename: Alain
authors.initials: A
authors.lastname: Puech
authors.affiliation: INSERM U862, Neurocentre Magendie, Bordeaux, France.
authors.forename: Pierre Vincenzo
authors.initials: PV
authors.lastname: Piazza
mesh_terms: D000328:Adult; D000480:Alkynes; D048588:Benzoxazines / Q000493:pharmacokinetics / Q000627:therapeutic use*; D003521:Cyclopropanes; D018450:Disease Progression; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D017430:Prostate-Specific Antigen; C098320:efavirenz