Does IGFR1 inhibition result in increased muscle mass loss in patients undergoing treatment for pancreatic cancer?

David R. Fogelman, Holly Holmes, Khalil Mohammed, Matthew H.G. Katz, Carla M. Prado, Jessica Lieffers, Naveen Garg, Gauri R. Varadhachary, Rachna Shroff, Michael J. Overman, Christopher Garrett, Robert A. Wolff, Milind Javle

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Background: IGF-1 plays a role in the growth of multiple tumor types, including pancreatic cancer. IGF-1 also serves as a growth factor for muscle. The impact of therapeutic targeting of IGF-1 on muscle mass is unknown.

Methods: We evaluated muscle mass at L3 in patients enrolled in a randomized phase II study of MK-0646 (M), a monoclonal antibody directed against the IGF-1 protein, in patients with metastatic pancreatic cancer (MPC). Two different doses of M were tested, 5 and 10 mg/kg. We used the Slice-o-matic (ver 4.3) software to segregate CT images into muscle and fat components and measured muscle area (cm2) at baseline and after 2 and 4 months of treatment. Patients received either gemcitabine with erlotinib (G + E), G + E + M, or G + M. Differences between the groups were compared using t tests.

Results: Fifty-three patients had both baseline and 2-month imaging available for analysis. Of these, 42 received M with their chemo, and 11 had G + E only. After 2 months of treatment, both groups demonstrated decrease in muscle mass. G + E patients lost 5.6 % of muscle mass; M patients lost 9.1 and 8.6 % after treatment with 5 and 10 mg/kg, respectively (p = 0.53). Patients demonstrating a response lost less muscle (median 4.6 %) than those with stable disease (9.6 %) and progressive disease (8.9 %, p = 0.14). Muscle retention from baseline to 2-month imaging, defined as loss of <6 cm2 of muscle, correlated with better survival than those patients demonstrating a muscle loss (HR 0.51, p = 0.03).

Conclusions: MPC patients can be expected to lose muscle mass even while having clinical benefit (PR or SD) from chemotherapy. Muscle loss correlated with a risk of study drop-out and death. There was a non-significant trend toward greater muscle mass loss in patients on anti-IGF-1R therapy. However, it is unclear if this loss translates into functional differences between patients.

Original languageEnglish (US)
Pages (from-to)307-313
Number of pages7
JournalJournal of Cachexia, Sarcopenia and Muscle
Volume5
Issue number4
DOIs
StatePublished - Nov 26 2014
Externally publishedYes

Keywords

  • Adenocarcinoma
  • Cachexia
  • IGF
  • Insulin Growth Factor
  • Pancreatic cancer
  • Sarcopenia

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Physiology (medical)

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