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Supportive Care in Cancer

, Volume 21, Issue 9, pp 2409–2415 | Cite as

Effect of ghrelin and anamorelin (ONO-7643), a selective ghrelin receptor agonist, on tumor growth in a lung cancer mouse xenograft model

  • R. NorthrupEmail author
  • K. Kuroda
  • E. Manning Duus
  • S. Routt Barnes
  • L. Cheatham
  • T. Wiley
  • C. Pietra
Original Article

Abstract

Purpose

Anamorelin (ONO-7643) is an orally active ghrelin receptor agonist in development for non-small cell lung cancer (NSCLC)-related anorexia/cachexia. It displays both orexigenic and anabolic properties via ghrelin mimetic activity and transient increases in growth hormone (GH). However, increasing GH and insulin-like growth factor-1 in cancer patients raises concerns of potentially stimulating tumor growth. Therefore, we investigated the effect of ghrelin and anamorelin on tumor growth in a murine NSCLC xenograft model.

Methods

Female nude mice (15–21/group) with established A549 tumors were administered ghrelin (2 mg/kg i.p.), anamorelin (3, 10, or 30 mg/kg p.o.), or vehicle controls daily for 28 days. Tumor growth, food consumption, and body weight were monitored. Murine growth hormone (mGH) and murine insulin-like growth factor-1 (mIGF-1) were measured in plasma.

Results

Tumor growth progressed throughout the study, with no significant differences between treatment groups. Daily food consumption was also relatively unchanged, while the percentage of mean body weight gain at the end of treatment was significantly increased in animals administered 10 and 30 mg/kg compared with controls (p < 0.01). Peak mGH levels were significantly higher in ghrelin- and anamorelin-treated animals than in controls, while peak mIGF-1 levels were slightly elevated but not statistically significant. All regimens were well tolerated.

Conclusions

These findings demonstrate that neither anamorelin nor ghrelin promoted tumor growth in this model, despite increased levels of mGH and a trend of increased mIGF-1. Together with anamorelin’s ability to increase body weight, these results support the clinical development of ghrelin receptor agonist treatments for managing NSCLC-related anorexia/cachexia.

Keywords

Anamorelin Cachexia Ghrelin Growth hormone IGF-1 Non-small cell lung cancer 

Notes

Acknowledgments

This study was co-sponsored by Helsinn and Ono Pharmaceutical Co., Ltd, and conducted at Charles River Discovery Research Services, Morrisville, NC, USA (Piedmont Research Center). The authors would like to acknowledge Alan Meshaw for his contribution to statistical analysis. Editorial assistance was provided by Elena Palmesino (Helsinn Healthcare, Lugano, Switzerland) and Sandra Mendes (TRM Oncology, The Hague, The Netherlands), funded by Helsinn.

Conflicts of interest

Robert Northrup and Elizabeth Manning Duus are employees of Helsinn Therapeutics (U.S.), Inc, and Claudio Pietra is an employee of Helsinn Healthcare. Ken Kuroda was an employee of Ono Pharmaceuticals. Sheri Routt Barnes, Lynn Cheatham, and Tim Wiley are employees of Charles River Discovery Research Services, a company which was paid by Helsinn and Ono to conduct this study. The authors have full control of the primary data and agree to allow the journal to review their data if requested.

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Copyright information

© The Author(s) 2013

Open Access This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.

Authors and Affiliations

  • R. Northrup
    • 1
    • 5
    Email author
  • K. Kuroda
    • 2
  • E. Manning Duus
    • 1
  • S. Routt Barnes
    • 3
  • L. Cheatham
    • 3
  • T. Wiley
    • 3
  • C. Pietra
    • 4
  1. 1.Research and DevelopmentHelsinn Therapeutics (U.S.), Inc.BridgewaterUSA
  2. 2.Safety Research LaboratoriesOno PharmaceuticalFukuiJapan
  3. 3.Charles River Discovery Research ServicesMorrisvilleUSA
  4. 4.Research and Preclinical DevelopmentHelsinn HealthcareLuganoSwitzerland
  5. 5.Safety AssessmentHelsinn Therapeutics (U.S.), Inc.BridgewaterUSA

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