title: A Study of Combination Bicalutamide and Raloxifene for Patients With Castration-Resistant Prostate Cancer.
abstract: Prostate tissue expresses 2 estrogen receptor (ER) isoforms, ER-α and ER-β, and estrogen-based therapies have shown activity in preclinical studies. Raloxifene, a selective ER modulator, has inhibited the growth of prostate cancer xenograft models and was tested in a phase II trial of castration-resistant prostate cancer (CRPC), with some patients achieving stable disease. However, no studies have examined the safety of the combination of bicalutamide plus raloxifene for CRPC. Therefore, we investigated the safety of treatment with bicalutamide plus raloxifene in patients with CRPC in an initial study.
  
  
  
  We conducted a study to evaluate the toxicity (primary endpoint) of the combination of bicalutamide (50 mg) and raloxifene (60 mg) in 28-day cycles (maximum, 6 cycles) in men with progressive CRPC. The secondary endpoint, quality of life (QOL), was assessed by patients using a 6-item linear analog self-assessment or hormonal domain scale of the Expanded Prostate Cancer Index Composite.
  
  
  
  We enrolled 18 patients with CRPC in the study to evaluate the safety of, and patient assessment of QOL (mental, physical, social, emotional, and spiritual) with, bicalutamide plus raloxifene therapy. No grade 3 or 4 adverse events occurred. None of the 18 patients required dose reductions. The patient assessment of QOL showed no statistically significant changes after 2 treatment cycles. The median progression-free survival with bicalutamide plus raloxifene was 1.9 months (95% confidence interval, 1.8-2.8 months).
  
  
  
  The results of the present study have shown that bicalutamide/raloxifene treatment is well tolerated. However, limited clinical activity occurred in men with CRPC who had previously undergone secondary hormonal therapy or chemotherapy.
authors: Division of Hematology and Medical Oncology, Mayo Clinic Arizona, Phoenix, AZ.
authors: Thai H
authors: TH
authors: Ho
authors: Department of Urology, Mayo Clinic Arizona, Phoenix, AZ.
authors: Rafael
authors: R
authors: Nunez-Nateras
authors: Department of Urology, Mayo Clinic Arizona, Phoenix, AZ.
authors: Yue-Xian
authors: YX
authors: Hou
authors: Division of Hematology and Medical Oncology, Mayo Clinic Arizona, Phoenix, AZ.
authors: Alan H
authors: AH
authors: Bryce
authors: Division of Hematology and Medical Oncology, Mayo Clinic Arizona, Phoenix, AZ.
authors: Donald W
authors: DW
authors: Northfelt
authors: Department of Biostatistics, Mayo Clinic Arizona, Scottsdale, AZ.
authors: Amylou C
authors: AC
authors: Dueck
authors: Division of Hematology and Medical Oncology, Mayo Clinic Arizona, Phoenix, AZ.
authors: Bryan
authors: B
authors: Wong
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic Arizona, Phoenix, AZ.
authors: Melissa L
authors: ML
authors: Stanton
authors: Division of Hematology and Medical Oncology, Mayo Clinic Florida, Jacksonville, FL.
authors: Richard W
authors: RW
authors: Joseph
authors: Department of Urology, Mayo Clinic Arizona, Phoenix, AZ. Electronic address: Castle.Erik@mayo.edu.
authors: Erik P
authors: EP
authors: Castle
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000813:Anilides / Q000008:administration & dosage / Q000009:adverse effects*; D004338:Drug Combinations; D004965:Estrogen Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage / Q000009:adverse effects*; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy*; D011788:Quality of Life; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects*; D016019:Survival Analysis; D014105:Tosyl Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome
chemical_list: D000813:Anilides; D004338:Drug Combinations; D004965:Estrogen Antagonists; D009570:Nitriles; D014105:Tosyl Compounds; D020849:Raloxifene Hydrochloride; C053541:bicalutamide
keywords: Androgen receptor; Bicalutamide; Castration resistant prostate cancer; Estrogen receptor; Prostate; Raloxifene