Cancer Palliative Care and Anabolic Therapies Aminah Jatoi, M.D. Professor of Oncology Mayo Clinic, Rochester, Minnesota USA • 2 Androgens • Creatine • Comments von Haehling S, et al, 2017 Oxandrolone: androgen that causes less virilization oxandrolone RANDOMIZE megestrol acetate #1: Oxandrolone (Lesser, et al, ASCO abstract 9513; 2008) • N=155 patients receiving chemotherapy • oxandrolone (10 mg twice a day x 12 weeks) versus megestrol acetate (800 mg/day x 12 weeks) • oxandrolone led to – a non-statistically significant increase in lean body mass (bioelectrical impedance) at 12 weeks (2.67 versus 0.82 pounds with megestrol acetate, p = 0.12), but – a decrease in overall weight as compared with megestrol acetate (-3.3 versus +5.8 pounds, respectively). • more oxandrolone patients dropped out prior to completing 12 weeks (63% versus 39 %). #2: Oxandrolone (von Roenn, et al, ASCO, 2003) • N=131 • Single arm • 81% of patients gained/maintained weight • Safe (PRIMARY ENDPOINT): 19% edema; 18% dyspnea; mild liver function test abnormalities #3: Oxandrolone: placebo controlled trial • results unknown SUMMARY OF OXANDROLONE: • Multiple studies (not yet peer-reviewed) • Hints of augmentation of lean tissue • High drop out in the phase 3 oxandrolone arm raises concern Enobosarm: selective androgen receptor modulator (less virilizing) ENOBOSARM RANDOMIZE* PLACEBO *All patients had non-small cell lung cancer, and chemotherapy was given concomittantly. percentage of subjects at day 84 with stair climb power change >=10% from their baseline value percentage of subjects at day 84 with lean body mass change >=0% from their baseline value SUMMARY OF ENOBOSARM: • Leads to incremental lean body mass, but functionality not demonstrated • Pivotal registration trial (not yet peer- reviewed (but FDA-reviewed….)) • 2 Androgens • Creatine • Comments Creatine: an amino acid derivative This study was funded by R21CA098477 and the Alliance for Clinical Trials NCORP grant. RATIONALE • creatine: amino acid derivative • reportedly, used extensively to enhance athletic performance • improves muscle mass and muscle functionality in older individuals and patients with muscular dystrophy von Haehling S, et al, 2017 Creatine and Lean Tissue in Older Adults (Chilibeck, et al, 2017) Creatine and Chest Press Strength in Older Adults (Chilibeck, et al, 2017) Creatine and Leg Press Strength in Older Adults (Chilibeck, et al, 2017) Improved Muscle Functionality in Muscular Dystrophy with Creatine (Kley, et al 2013) Creatine RANDOMIZE* PLACEBO *All patients could receive chemotherapy or radiation and were stratified based on anticipated therapy. Annals of Oncology, 2017 PATIENT-REPORTED OUTCOMES: No statistically significant differences in appetite scores PATIENT-REPORTED OUTCOMES: No statistically significant differences in activity scores fist-grip and body composition (bioelectrical impedance): no statistically significant difference between arms SUMMARY OF CREATINE: • Androgens • Creatine • Comments Comment #1 Manifestations of publication bias…? Comment #2 Adding other therapy…? Comment #3 The importance of functionality…? THANK YOU!!.