Open AccessA Phase II Trial Evaluating the Efficacy and Safety of Efavirenz in Metastatic Castration‐Resistant Prostate Cancer
Author(s) -
Houédé Nadine,
Pulido Marina,
Mourey Loic,
Joly Florence,
Ferrero JeanMarc,
Bellera Carine,
Priou Frank,
Lalet Caroline,
LarocheClary Audrey,
Raffin Mireille Canal,
Ichas François,
Puech Alain,
Piazza Pierre Vincenzo
Publication year - 2014
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2014-0345
Subject(s) - efavirenz , medicine , prostate cancer , pharmacokinetics , oncology , confidence interval , reverse transcriptase inhibitor , enzalutamide , prostate specific antigen , urology , cancer , viral load , immunology , human immunodeficiency virus (hiv) , antiretroviral therapy , androgen receptor
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. 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.