A phase II trial evaluating the efficacy and safety of efavirenz in metastatic castration-resistant prostate cancer
The Oncologist. 2014-10-29; 19(12): 1227-1228
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Houédé N(1), Pulido M(2), Mourey L(3), Joly F(4), Ferrero JM(5), Bellera C(2),Priou F(6), Lalet C(2), Laroche-Clary A(7), Raffin MC(8), Ichas F(7), Puech A(7),
(1)Department of Medical Oncology, Nimes University Hospital, Nimes, France;.
(2)Clinical Research and Clinical Epidemiology Unit, Bergonié Cancer Institute, Bordeaux, France;
(3)Department of Oncology, Claudius Régaud Cancer Center, Toulouse, France;
(4)Department of Medical Oncology, François Baclesse Cancer Center, Caen, France;
(5)Department of Medical Oncology, Antoine Lacassagne Cancer Center, Nice, France;
(6)Department of Medical Oncology, CHD La Roche sur Yon, La Roche sur Yon, France;
(7)Alienor Farma, Parc Scientifique Unitec 1, Pessac, France;
(8)Centre Hospitalier de Pellegrin, Laboratoire de Pharmacologie et Toxicologie, Bordeaux, France;
(9)INSERM U862, Neurocentre Magendie, Bordeaux, France.
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
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.
CONCLUSION: 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.