title: Uncontrolled diabetes predicts poor response to novel antiandrogens.
abstract: Metabolic abnormalities including hyperglycemia and hyperlipidemia have been associated with worse prognosis of prostate cancer (PCa), but there are limited data regarding their impact on the prognosis of castrate-resistant prostate cancer (CRPC) and the response of novel antiandrogens, namely abiraterone acetate (AA) and enzalutamide. Retrospective analysis of 61 patients with CRPC on AA or enzalutamide, treated at the Boston Medical Center, was performed. We evaluated hemoglobin A1c (HbA1c), HDL, LDL, Triglycerides and BMI within 2months before the initiation of treatment with AA or enzalutamide and progression-free survival (PFS) under this treatment. Regression analysis and analysis of variance were used to evaluate the data. HbA1c levels were found to predict adversely the PFS on the novel agents (df (1, 37), P=0.00, R(2)=0.40, coeff=-3.28). The Kaplan-Meier analysis showed that there is significant difference in survival between the HbA1c 4.7-5.9% compared with patients with HbA1c 7.8-11.6% (6.72±1.3months, log rank test P<0.0001) LDL (P=0.07), HDL (P=0.14), and triglycerides (P=0.33) were not found to predict PFS. BMI predicted PFS positively (df (1.59), P=0.02, R(2)=0.09, coeff=0.03), but not independently of HbA1c (P=0.07). No significant implications of social and family history, previous chemotherapy regimen, and Gleason score with PFS were found. Multiple markers of patients' health state were not associated with HbA1c values. Uncontrolled diabetes can predict for poor response of CRPC patients to AA and enzalutamide determining PFS under this treatment. Elevated BMI can positively affect PFS at this stage of disease.
authors: General Internal Medicine DepartmentBoston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA.
authors: Theodoros
authors: T
authors: Karantanos
authors: Infectious Diseases DivisionWarren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
authors: Styliani
authors: S
authors: Karanika
authors: Hematology-Oncology DepartmentBoston Medical Center, Boston University School of Medicine, Boston, Massachusetts, USA Gretchen.Gignac@bmc.org.
authors: Gretchen
authors: G
authors: Gignac
mesh_terms: D000069501:Abiraterone Acetate / Q000627:therapeutic use*; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D001549:Benzamides; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy*; D018572:Disease-Free Survival; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011379:Prognosis; D064129:Prostatic Neoplasms, Castration-Resistant / Q000097:blood / Q000188:drug therapy*; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
chemical_list: D000069501:Abiraterone Acetate; D000726:Androgen Antagonists; D001549:Benzamides; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D009570:Nitriles; D010669:Phenylthiohydantoin; D014280:Triglycerides; C517652:hemoglobin A1c protein, human; C540278:enzalutamide
keywords: HbA1c; abiraterone acetate; castrate-resistant prostate cancer; diabetes; enzalutamide