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

• Author(s) / Creator(s)

  • Shroff, R.
  • Katz, M. H.
  • Overman, M. J.
  • Khalil, M.
  • Lieffers, J.
  • Varadhachary, G. R.
  • Fogelman, D.
  • Javle, M.
  • Holmes, H.
  • Prado, C. M.

• 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

• Subjects / Keywords

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

• Type of Item

  Article (Published)

• DOI

  https://doi.org/10.7939/R3C24R18W

• License

  Attribution-NonCommercial 4.0 International