title: Does IGFR1 inhibition result in increased muscle mass loss in patients undergoing treatment for pancreatic cancer?
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 (cm(2)) 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 cm(2) 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.
authors.affiliation: M.D. Anderson Cancer Center, 1515 Holcombe Drive, Houston, TX, 77030, USA, dfogelman@mdanderson.org.
authors.forename: David R
authors.initials: DR
authors.lastname: Fogelman
authors.forename: Holly
authors.initials: H
authors.lastname: Holmes
authors.forename: Khalil
authors.initials: K
authors.lastname: Mohammed
authors.forename: Matthew H G
authors.initials: MH
authors.lastname: Katz
authors.forename: Carla M
authors.initials: CM
authors.lastname: Prado
authors.forename: Jessica
authors.initials: J
authors.lastname: Lieffers
authors.forename: Naveen
authors.initials: N
authors.lastname: Garg
authors.forename: Gauri R
authors.initials: GR
authors.lastname: Varadhachary
authors.forename: Rachna
authors.initials: R
authors.lastname: Shroff
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Overman
authors.forename: Christopher
authors.initials: C
authors.lastname: Garrett
authors.forename: Robert A
authors.initials: RA
authors.lastname: Wolff
authors.forename: Milind
authors.initials: M
authors.lastname: Javle
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