A randomized trial of adjunct testosterone for cancer‐related muscle loss in men and women

Abstract

BackgroundCancer cachexia negatively impacts cancer‐related treatment options, quality of life, morbidity, and mortality, yet no established therapies exist. We investigated the anabolic properties of testosterone to limit the loss of body mass in late stage cancer patients undergoing standard of care cancer treatment.MethodsA randomized, double‐blind, placebo‐controlled phase II clinical trial was undertaken to assess the potential therapeutic role of adjunct testosterone to limit loss of body mass in patients with squamous cell carcinoma of the cervix or head and neck undergoing standard of care treatment including chemotherapy and chemoradiation. Patients were randomly assigned in blocks to receive weekly injections of either 100 mg testosterone enanthate or placebo for 7 weeks. The primary outcome was per cent change in lean body mass, and secondary outcomes included assessment of quality of life, tests of physical performance, muscle strength, daily activity levels, resting energy expenditure, nutritional intake, and overall survival.ResultsA total of 28 patients were enrolled, 22 patients were studied to completion, and 21 patients were included in the final analysis (12 placebo, nine testosterone). Adjunct testosterone increased lean body mass by 3.2% (95% confidence interval [CI], 0–7%) whereas those receiving placebo lost 3.3% (95% CI, −7% to 1%, P = 0.015). Although testosterone patients maintained more favourable body condition, sustained daily activity levels, and showed meaningful improvements in quality of life and physical performance, overall survival was similar in both treatment groups.ConclusionsIn patients with advanced cancer undergoing the early phase of standard of care therapy, adjunct testosterone improved lean body mass and was also associated with increased quality of life, and physical activity compared with placebo.

A multi‐targeted treatment approach to cancer cachexia: Auckland's Cancer Cachexia evaluating Resistance Training (ACCeRT) trial

“…During this time, there has been a change in the consideration of cachexia from a ‘very late change’ and inescapable event to ‘an early phenomenon’ with signs of cachexia present upon primary cancer diagnosis even if weight loss has not yet occurred. This has led to the recent shift in developing effective treatments aimed at preventing rather than reversing the symptoms, as seen in the earlier studies …”

“…[4][5][6] Recent publications have shown progress in a number of areas including the ghrelin receptor agonist anamorelin, which possesses both anabolic and appetite-stimulating properties, as per ROMANA 1, 2, and 3 studies, 7,8 the novel non-selective beta-blocker with central 5-HT1a and partial β2 receptor agonist espindolol, which possesses both anabolic and anti-catabolic properties, as per ACT-ONE study, 9 and the anabolic properties of testosterone. 10 During this time, there has been a change in the consideration of cachexia from a 'very late change' and inescapable event to 'an early phenomenon' with signs of cachexia present upon primary cancer diagnosis even if weight loss has not yet occurred. This has led to the recent shift in developing effective treatments aimed at preventing rather than reversing the symptoms, as seen in the earlier studies.…”

Muscle radiodensity loss during cancer therapy is predictive for poor survival in advanced endometrial cancer

“…Wright et al reported that, in patients with advanced cancer undergoing early-phase standard-of-care therapy, 7 weeks of adjunct testosterone treatment improved lean body mass as well as the quality of life and physical activity. 68 Dieli-Conwright et al recently reported that combined resistance and aerobic exercises significantly attenuated sarcopenic obesity in patients with breast cancer. 69 A phase III clinical trial (NCT02330926) is currently evaluating whether multimodal interventions can improve the outcomes of cancer patients.…”

“…Wright et al . reported that, in patients with advanced cancer undergoing early‐phase standard‐of‐care therapy, 7 weeks of adjunct testosterone treatment improved lean body mass as well as the quality of life and physical activity . Dieli‐Conwright et al .…”

The evolution of body composition in oncology—epidemiology, clinical trials, and the future of patient care: facts and numbers

“…66 Therapies that utilize or target ghrelin, 67,68 androgen receptors, 69 interleukin-1α, 70,71 β receptor blockade, 72 testosterone, 73 and myostatin 74 have been evaluated in randomized clinical trials. 66 Therapies that utilize or target ghrelin, 67,68 androgen receptors, 69 interleukin-1α, 70,71 β receptor blockade, 72 testosterone, 73 and myostatin 74 have been evaluated in randomized clinical trials.…”