Anamorelin Shows Promise for Cancer Cachexia
By Will Boggs MD
NEW YORK (Reuters Health) - The selective ghrelin-receptor agonist anamorelin improves body mass and grip strength in patients with cancer cachexia, according to results of a small randomized trial.
Cancer anorexia-cachexia affects as many as 50% of patients with cancer, and nutritional supplementation alone cannot reverse the weight loss. Ghrelin blunts the effects of cachexia in animal models, but it requires parenteral administration and has a short half-life.
Dr. José M. Garcia from Michael E. DeBakey VA Medical Center and Baylor College of Medicine in Houston, Texas and colleagues tested 12 weeks of treatment with the orally available anamorelin on body mass, physical strength, and quality of life in 82 patients with cancer cachexia (44 randomized to anamorelin, 38 randomized to placebo).
Only 46 patients (23 in each group) completed the 12-week study. Most discontinuations were due to refusal to continue study participation (18 patients), the authors reported December 16th online in Lancet Oncology.
Among the 74 patients included in the efficacy analysis, total and lean body mass increased significantly among those assigned to anamorelin but decreased among those assigned to placebo. Fat mass decreases in both groups did not differ significantly.
Handgrip strength improved by an average 2.49 kg in the anamorelin group but decreased by 0.1 kg in the placebo group.
Quality of life as measured by the Anderson Symptom Assessment Scale total score - which ranges from 0 (worst imaginable) to 10 (no symptoms) - improved by an average 1.52 points with anamorelin while worsening by an average 5.13 points with placebo.
IGF-1 and IGFB-3 concentrations improved to a significantly greater extent in the anamorelin group, but mean values of C-reactive protein, interleukin 6, and TNF-alpha did not differ significantly between the treatment groups.
More anamorelin than placebo patients had adverse events and serious adverse events, but there were no deaths related to treatment.
"On the basis of these results, further testing of anamorelin on a larger scale is warranted," the researchers conclude. "Anamorelin is now being assessed in phase 3 studies investigating efficacy and safety in patients with non-small-cell lung cancer and cancer anorexia-cachexia syndrome."
Dr. Vickie E. Baracos from the University of Alberta in Edmonton, Alberta, Canada wrote an editorial related to this report. She told Reuters Health by email, "Despair or nihilism concerning our potential ability to treat cancer cachexia may not be justified. I would encourage everyone to take heart that cancer associated cachexia or cancer associated muscle wasting are manifestations of specific pathophysiology which we can understand and treat, just as we have understood and devised treatments for many other conditions."
"There are at this time no approved therapies for cancer-associated cachexia," she said. "However, there are a number of agents currently in phase 2 and in phase 3 clinical trials, including anamorelin, as well as interventions designed to activate the skeletal muscle androgen receptor or to inhibit the catabolic effects of activin/myostatin via the activin type II receptor. One or more of these agents may achieve criteria for approval in the foreseeable future."
"I hope that physicians involved in the care of patients with advanced cancer would open cachexia clinical trials at their centers and thereby make an opportunity to accrue patients to ongoing and forthcoming randomized clinical trials, so that we can obtain evidence necessary and essential to underpinning the first approved therapy," Dr. Baracos said.
Helsinn Therapeutics sponsored the trial, employed four of the seven authors, and provided funding to Dr. Garcia.
Dr. Garcia did not respond to a request for comments.
SOURCE: https://bit.ly/178igPH
Lancet Oncol 2014.
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