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Therapeutic potential of anamorelin, a novel, oral ghrelin mimetic, in patients with cancer-related cachexia: a multicenter, randomized, double-blind, crossover, pilot study

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Abstract

Purpose

Cachexia in cancer adversely affects patients' perception of symptoms, well-being, and response to therapy, and shortens survival. Anamorelin, an oral mimetic of ghrelin, has been shown to increase body weight and anabolic hormone levels in healthy volunteers and is being investigated to treat cancer cachexia.

Methods

This multicenter, double-blind, placebo-controlled, crossover study evaluated the effects of anamorelin in 16 patients with different cancers and cachexia. Patients were randomly assigned to anamorelin 50 mg/day or placebo for 3 days. A 3- to 7-day washout period followed and then treatments were switched. Assessments included body weight, appetite, food intake, growth hormone (GH) levels, patient-reported symptom assessments (e.g., the Anderson Symptom Assessment Scale [ASAS] and also an inclusion criterion), and safety.

Results

Anamorelin significantly increased body weight compared with placebo (0.77 kg vs. −0.33 kg). Food intake increased compared with placebo, but not significantly. GH significantly increased at all time points (0.5–4 h postdose). Insulin-like growth factor-1 (IGF-1) significantly increased by 54.09 ng/mL with anamorelin treatment compared with −3.56 ng/mL for placebo; significant changes in insulin-like growth factor-binding protein 3 (IGFBP-3) were 0.75 μg/mL vs. −0.19 μg/mL, respectively. Patient-reported symptoms, including appetite as measured by ASAS, significantly improved with anamorelin (8.1 vs. 1.0 for placebo). Adverse events (AEs) in four patients were possibly or probably related to anamorelin: hyperglycemia (two patients), nausea (one patient), and dizziness (one patient). Most AEs were mild; no patients withdrew due to AEs.

Conclusions

Anamorelin showed significant metabolic, clinical, and patient-rated effects in cancer cachexia. Further studies are warranted.

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Acknowledgments

Support for developing this manuscript was provided by Helsinn Therapeutics (US), Inc., and copyediting, editorial assistance, and production assistance was provided by Paul V. Shea and The Curry Rockefeller Group, LLC (Tarrytown, NY). The authors thank Wei Du, Ph.D. (Norristown, PA) for reviewing the statistical methods and verifying data.

Funding

This research was sponsored by Helsinn Therapeutics (US), Inc.

Disclosure

José M. Garcia has received research funding from Helsinn Therapeutics (US), Inc. and Aeterna Zentaris Inc., and receives research support from the Department of Veterans Affairs (MERIT awards BX000507 and CX00174). John Friend and Suzan Allen are employees of Helsinn Therapeutics (US), Inc.

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Correspondence to José M. Garcia.

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The authors declare that they have full control of the primary data and agree to allow the journal to review these data if requested.

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Garcia, J.M., Friend, J. & Allen, S. Therapeutic potential of anamorelin, a novel, oral ghrelin mimetic, in patients with cancer-related cachexia: a multicenter, randomized, double-blind, crossover, pilot study. Support Care Cancer 21, 129–137 (2013). https://doi.org/10.1007/s00520-012-1500-1

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