Testosterone effective in combating cachexia in cancer patients

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TestosteroneIn patients with advanced cancer undergoing early standard of care therapy, adjunct testosterone improved lean body mass and was also associated with increased quality of life, found a small, five-year National Cancer Institute funded study.

Many cancer patients suffer from a loss of body mass known as cachexia. Approximately 20% of cancer related deaths are attributed to the syndrome of cachexia, which in cancer patients is often characterised by a rapid or severe loss of fat and skeletal muscle. Dr Melinda Sheffield-Moore, professor and head of the department of health and kinesiology, along with researchers at University of Texas Medical Branch, recently published research showing that the hormone testosterone is effective at combating cachexia in cancer patients and improving quality of life.

These findings are important, as there are currently no established therapies targeting this loss of skeletal muscle, and without an intervention, patients lose muscle function and become fatigued and weakened.

“We hoped to demonstrate these patients would go from not feeling well enough to even get out of bed to at least being able to have some basic quality of life that allows them to take care of themselves and receive therapy,” Sheffield-Moore said.

Sheffield-Moore said doctors sought her expertise in nutrition and metabolism when patients were losing tremendous amounts of weight from cancer cachexia. She said that previous nutrition-focused treatment failed to combat this severe loss of body mass, which led her team to investigate the hormone testosterone as an option to combat the often debilitating consequences of cancer cachexia.

“We already know that testosterone builds skeletal muscle in healthy individuals, so we tried using it in a population at a high risk of muscle loss, so these patients could maintain their strength and performance status to be able to receive standard cancer therapies.” Sheffield-Moore said.

During this five-year National Cancer Institute funded study, patients with a type of cancer known as squamous cell carcinoma were treated with standard of care chemotherapy and/or radiation in addition to seven weeks of treatment with either testosterone or placebo. Throughout the study, patients were monitored for changes in physical activity, muscle and fat mass and tested for physical performance.

Patients in this study receiving testosterone maintained total body mass and increased lean body mass by 3.2%. Sustaining body mass is important considering most patients experience a 20% decrease in body mass or more depending upon the type of cancer.

“Patients randomised to the group receiving testosterone as an adjuvant to their standard of care chemotherapy and/or radiation treatment also demonstrated enhanced physical activity,” Sheffield-Moore said. “They felt well enough to get up and take care of some of their basic activities of daily living, like cooking, cleaning and bathing themselves.”

Additionally, Sheffield-Moore’s lab is currently analysing skeletal muscle proteomic data from this study. “What the proteome (profile of proteins found in the muscle) tells us is which particular proteins in the skeletal muscles were either positively or negatively affected by testosterone or by cancer, respectively,” Sheffield-Moore said. “It allows us to begin to dig into the potential mechanisms behind cancer cachexia.”

Sheffield-Moore hopes this research will help cancer patients increase quality of life and maintain eligibility to receive standard of care therapy if cachexia ensues.

Background: Cancer 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.
Methods: A 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.
Results: A 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.
Conclusions: In 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.

Traver J Wright, E Lichar Dillon, William J Durham, Albert Chamberlain, Kathleen M Randolph, Christopher Danesi, Astrid M Horstman, Charles R Gilkison, Maurice Willis, Gwyn Richardson, Sandra S Hatch, Daniel C Jupiter, Susan McCammon, Randall J Urban, Melinda Sheffield-Moore

Texas A&M University material
Journal of Cachexia, Sarcopenia and Muscle abstract

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