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Permanent link (DOI): https://doi.org/10.7939/R3C24R18W

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

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Author or creator
Fogelman, D.
Holmes, H.
Khalil, M.
Katz, M. H.
Prado, C. M.
Lieffers, J.
Varadhachary, G. R.
Shroff, R.
Overman, M. J.
Javle, M.
Additional contributors
Subject/Keyword
Sarcopenia
Insulin Growth Factor
Adenocarcinoma
Cachexia
IGF
Pancreatic Cancer
Type of item
Journal Article (Published)
Language
English
Place
Time
Description
BackgroundIGF-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.MethodsWe 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.ResultsFifty-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).ConclusionsMPC 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.
Date created
2014
DOI
doi:10.7939/R3C24R18W
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Attribution-NonCommercial 4.0 International
Citation for previous publication
Fogelman, D., Holmes, H., Khalil, M., Katz, M. H., Prado, C. M., Lieffers, J., Varadhachary, G. R., Shroff, R., Overman, M. J., & Javle, M. (2014). Does IGFR1 inhibition result in increased muscle mass loss in patients undergoing treatment for pancreatic cancer? Journal of Cachexia, Sarcopenia and Muscle, 5(4), 307-313.  http://doi.org/10.1007/s13539-014-0145-y

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