title: A phase 2 clinical trial of everolimus plus bicalutamide for castration-resistant prostate cancer.
abstract: The mammalian target of rapamycin (mTOR) pathway is up-regulated in castration-resistant prostate cancer (CRPC). Nevertheless, inhibition of mTOR is ineffective in inducing apoptosis in prostate cancer cells, likely because of the compensatory up-regulation of the androgen receptor (AR) pathway.
  
  
  
  Patients who were eligible for this study had to have progressive CRPC with serum testosterone levels <50 ng/dL. No prior bicalutamide (except to prevent flare) or everolimus was allowed. Treatment included oral bicalutamide 50 mg and oral everolimus 10 mg, both once daily, with a cycle defined as 4 weeks. The primary endpoint was the prostate-specific antigen (PSA) response (≥30% reduction) from baseline. A sample size of 23 patients would have power of 0.8 and an α error of .05 (1-sided) if the combination had a PSA response rate of 50% versus a historic rate of 25% with bicalutamide alone.
  
  
  
  Twenty-four patients were enrolled. The mean age was 71.1 years (range, 53.0-87.0 years), the mean PSA level at study entry was 43.4 ng/dL (range, 2.5-556.9 ng/dL), and the mean length of treatment was 8 cycles (range, 1.0-23.0 cycles). Of 24 patients, 18 had a PSA response (75%; 95% confidence interval [CI], 0.53-0.90), whereas 15 (62.5%; 95% CI, 0.41-0.81) had a PSA decrease ≥50%. The median overall survival was 28 months (95% CI, 14.1-42.7 months). Fourteen patients (54%; 95% CI, 0.37-0.78) developed grade 3 (13 patients) or grade 4 (1 patient with sepsis) adverse events that were attributable to treatment.
  
  
  
  The combination of bicalutamide and everolimus has encouraging efficacy in men with bicalutamide-naive CRPC, thus warranting further investigation. A substantial number of patients experienced everolimus-related toxicity. Cancer 2016;122:1897-904. © 2016 American Cancer Society.
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of California Davis, Sacramento, California.
authors.forename: Helen
authors.initials: H
authors.lastname: Chow
authors.affiliation: Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, California.|Veterans Affairs Northern California Health Care System-Mather, Mather, California.|Department of Urology, University of California Davis, Sacramento, California.
authors.forename: Paramita M
authors.initials: PM
authors.lastname: Ghosh
authors.affiliation: Department of Urology, University of California Davis, Sacramento, California.
authors.forename: Ralph
authors.initials: R
authors.lastname: deVere White
authors.affiliation: Department of Urology, University of California Davis, Sacramento, California.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Evans
authors.affiliation: Department of Urology, University of California Davis, Sacramento, California.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Dall'Era
authors.affiliation: Department of Urology, University of California Davis, Sacramento, California.
authors.forename: Stanley A
authors.initials: SA
authors.lastname: Yap
authors.affiliation: Department of Public Health Sciences, University of California, Davis, California.
authors.forename: Yueju
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Public Health Sciences, University of California, Davis, California.
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Beckett
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of California Davis, Sacramento, California.
authors.forename: Primo N
authors.initials: PN
authors.lastname: Lara
authors.affiliation: Department of Internal Medicine, Division of Hematology/Oncology, University of California Davis, Sacramento, California.|Veterans Affairs Northern California Health Care System-Mather, Mather, California.|Department of Urology, University of California Davis, Sacramento, California.
authors.forename: Chong-Xian
authors.initials: CX
authors.lastname: Pan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000008:administration & dosage; D000813:Anilides / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068338:Everolimus / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D011944:Receptors, Androgen / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D014105:Tosyl Compounds / Q000008:administration & dosage
chemical_list: C410798:AR protein, human; D000726:Androgen Antagonists; D000813:Anilides; D009570:Nitriles; D011944:Receptors, Androgen; D014105:Tosyl Compounds; D000068338:Everolimus; C053541:bicalutamide; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: bicalutamide; castration-resistant prostate cancer; everolimus; mammalian target of rapamycin (mTOR); urology