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

Journal of Cachexia, Sarcopenia and Muscle

Fogelman David R.⁴  Holmes Holly⁴  Mohammed Khalil²  Katz Matthew H. G.⁴  Prado Carla M.¹  Lieffers Jessica³  Garg Naveen⁴  Varadhachary Gauri R.⁴  Shroff Rachna⁴  Overman Michael J.⁴  Garrett Christopher⁴  Wolff Robert A.⁴ 

[1] Florida State University, Tallahassee, FL;Forrest Hills Hospital, Queens, NY;School of Public Health Systems, University of Waterloo, Waterloo, ON;M.D. Anderson Cancer Center, Houston, TX

关键词: Pancreatic cancer;    Adenocarcinoma;    Sarcopenia;    IGF;    Insulin Growth Factor;    Cachexia;   

DOI  :  10.1007/s13539-014-0145-y

来源: Wiley

【 摘 要 】

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.

【 授权许可】

CC BY-NC   
© 2014 The Authors. Published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders

Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.