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Pilot clinical trial of macimorelin to assess safety and efficacy in patients with cancer cachexia

BACKGROUND: Cancer cachexia is associated with reduced body weight, appetite and quality of life (QOL) with no approved treatments. Growth hormone secretagogues like macimorelin have potential to mitigate these effects. METHODS: This pilot study assessed the safety and efficacy of macimorelin for 1 ...

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Autores principales: Herodes, Megan, Anderson, Lindsey J., Shober, Samuel, Schur, Ellen A., Graf, Solomon A., Ammer, Nicola, Salas, Ramiro, Marcelli, Marco, Garcia, Jose M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067502/
https://www.ncbi.nlm.nih.gov/pubmed/36860137
http://dx.doi.org/10.1002/jcsm.13191
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author Herodes, Megan
Anderson, Lindsey J.
Shober, Samuel
Schur, Ellen A.
Graf, Solomon A.
Ammer, Nicola
Salas, Ramiro
Marcelli, Marco
Garcia, Jose M.
author_facet Herodes, Megan
Anderson, Lindsey J.
Shober, Samuel
Schur, Ellen A.
Graf, Solomon A.
Ammer, Nicola
Salas, Ramiro
Marcelli, Marco
Garcia, Jose M.
author_sort Herodes, Megan
collection PubMed
description BACKGROUND: Cancer cachexia is associated with reduced body weight, appetite and quality of life (QOL) with no approved treatments. Growth hormone secretagogues like macimorelin have potential to mitigate these effects. METHODS: This pilot study assessed the safety and efficacy of macimorelin for 1 week. Efficacy was defined a priori as 1‐week change in body weight (≥0.8 kg), plasma insulin‐like growth factor (IGF)‐1 (≥50 ng/mL) or QOL (≥15%). Secondary outcomes included food intake, appetite, functional performance, energy expenditure and safety laboratory parameters. Patients with cancer cachexia were randomized to 0.5 or 1.0 mg/kg macimorelin or placebo; outcomes were assessed non‐parametrically. RESULTS: Participants receiving at least one of either macimorelin dose were combined (N = 10; 100% male; median age = 65.50 ± 2.12) and compared with placebo (N = 5; 80% male; median age = 68.00 ± 6.19). Efficacy criteria achieved: body weight (macimorelin N = 2; placebo N = 0; P = 0.92); IGF‐1 (macimorelin N = 0; placebo N = 0); QOL by Anderson Symptom Assessment Scale (macimorelin N = 4; placebo N = 1; P = 1.00) or Functional Assessment of Chronic Illness Therapy‐Fatigue (FACIT‐F; macimorelin N = 3; placebo N = 0; P = 0.50). No related serious or non‐serious adverse events were reported. In macimorelin recipients, change in FACIT‐F was directly associated with change in body weight (r = 0.92, P = 0.001), IGF‐1 (r = 0.80, P = 0.01), and caloric intake (r = 0.83, P = 0.005), and inversely associated with change in energy expenditure (r = −0.67, P = 0.05). CONCLUSIONS: Daily oral macimorelin for 1 week was safe and numerically improved body weight and QOL in patients with cancer cachexia compared with placebo. Longer term administration should be evaluated for mitigation of cancer‐induced reductions in body weight, appetite and QOL in larger studies.
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spelling pubmed-100675022023-04-04 Pilot clinical trial of macimorelin to assess safety and efficacy in patients with cancer cachexia Herodes, Megan Anderson, Lindsey J. Shober, Samuel Schur, Ellen A. Graf, Solomon A. Ammer, Nicola Salas, Ramiro Marcelli, Marco Garcia, Jose M. J Cachexia Sarcopenia Muscle Original Articles BACKGROUND: Cancer cachexia is associated with reduced body weight, appetite and quality of life (QOL) with no approved treatments. Growth hormone secretagogues like macimorelin have potential to mitigate these effects. METHODS: This pilot study assessed the safety and efficacy of macimorelin for 1 week. Efficacy was defined a priori as 1‐week change in body weight (≥0.8 kg), plasma insulin‐like growth factor (IGF)‐1 (≥50 ng/mL) or QOL (≥15%). Secondary outcomes included food intake, appetite, functional performance, energy expenditure and safety laboratory parameters. Patients with cancer cachexia were randomized to 0.5 or 1.0 mg/kg macimorelin or placebo; outcomes were assessed non‐parametrically. RESULTS: Participants receiving at least one of either macimorelin dose were combined (N = 10; 100% male; median age = 65.50 ± 2.12) and compared with placebo (N = 5; 80% male; median age = 68.00 ± 6.19). Efficacy criteria achieved: body weight (macimorelin N = 2; placebo N = 0; P = 0.92); IGF‐1 (macimorelin N = 0; placebo N = 0); QOL by Anderson Symptom Assessment Scale (macimorelin N = 4; placebo N = 1; P = 1.00) or Functional Assessment of Chronic Illness Therapy‐Fatigue (FACIT‐F; macimorelin N = 3; placebo N = 0; P = 0.50). No related serious or non‐serious adverse events were reported. In macimorelin recipients, change in FACIT‐F was directly associated with change in body weight (r = 0.92, P = 0.001), IGF‐1 (r = 0.80, P = 0.01), and caloric intake (r = 0.83, P = 0.005), and inversely associated with change in energy expenditure (r = −0.67, P = 0.05). CONCLUSIONS: Daily oral macimorelin for 1 week was safe and numerically improved body weight and QOL in patients with cancer cachexia compared with placebo. Longer term administration should be evaluated for mitigation of cancer‐induced reductions in body weight, appetite and QOL in larger studies. John Wiley and Sons Inc. 2023-03-01 /pmc/articles/PMC10067502/ /pubmed/36860137 http://dx.doi.org/10.1002/jcsm.13191 Text en © 2023 Aeterna Zentaris GmbH. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Herodes, Megan
Anderson, Lindsey J.
Shober, Samuel
Schur, Ellen A.
Graf, Solomon A.
Ammer, Nicola
Salas, Ramiro
Marcelli, Marco
Garcia, Jose M.
Pilot clinical trial of macimorelin to assess safety and efficacy in patients with cancer cachexia
title Pilot clinical trial of macimorelin to assess safety and efficacy in patients with cancer cachexia
title_full Pilot clinical trial of macimorelin to assess safety and efficacy in patients with cancer cachexia
title_fullStr Pilot clinical trial of macimorelin to assess safety and efficacy in patients with cancer cachexia
title_full_unstemmed Pilot clinical trial of macimorelin to assess safety and efficacy in patients with cancer cachexia
title_short Pilot clinical trial of macimorelin to assess safety and efficacy in patients with cancer cachexia
title_sort pilot clinical trial of macimorelin to assess safety and efficacy in patients with cancer cachexia
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10067502/
https://www.ncbi.nlm.nih.gov/pubmed/36860137
http://dx.doi.org/10.1002/jcsm.13191
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