Regorafenib Is Associated With Increased Skeletal Muscle Loss Compared to TAS-102 in Metastatic Colorectal Cancer

Clin Colorectal Cancer. 2019 Jun;18(2):159-166.e3. doi: 10.1016/j.clcc.2019.04.003. Epub 2019 Apr 11.

Abstract

Background: Current guidelines of the National Comprehensive Cancer Network and the European Society of Medical Oncology recommend regorafenib or trifluridine/tipiracil (TAS-102) for third-line therapy of metastatic colorectal cancer (mCRC). We evaluated the impact of regorafenib and TAS-102 treatment on skeletal muscle dynamics and sarcopenia.

Patients and methods: This retrospective analysis was based on unselected, consecutive mCRC patients treated with regorafenib and/or TAS-102 during third or later line of therapy at our tertiary-care cancer center in Salzburg, Austria. The skeletal muscle index (SMI, cm2/m2) and sarcopenia were evaluated from cross-sectional computed tomographic images at the level of the third lumbar vertebra.

Results: Between January 2013 and April 2018, a total of 45 patients had received regorafenib and/or TAS-102. At initial mCRC diagnosis and at initiation of third-line therapy, 24% and 54% of patients presented with sarcopenia. A statistically significant skeletal muscle loss was observed during regorafenib treatment (median SMI change: -2.75 cm2/m2 [-6.3%]; P < .0001), which was not the case during TAS-102 therapy (-1.5 cm2/m2 [-3.5%]; P = .575). Furthermore, subclassification of patients into 3 groups-normal muscle mass, stable sarcopenia, and new-onset sarcopenia-at initiation of third-line therapy permitted discrimination of overall survival, with 1-year overall survival rates of 61%, 29%, and 16%, respectively (P = .04).

Conclusion: The frequency of sarcopenia increases during the course of mCRC and negatively affects survival. In contrast to TAS-102, regorafenib is associated with increased skeletal muscle loss during mCRC treatment and should therefore be used with caution in mCRC patients with preexisting sarcopenia or a history of recent weight loss.

Keywords: Cross-sectional image; Sarcopenia; Third-line therapy; Trifluridine/tipiracil; mCRC.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Austria
  • Colorectal Neoplasms / complications
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / mortality
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Humans
  • Lumbar Vertebrae
  • Male
  • Middle Aged
  • Muscle, Skeletal / diagnostic imaging
  • Muscle, Skeletal / drug effects
  • Phenylurea Compounds / administration & dosage
  • Phenylurea Compounds / adverse effects*
  • Pyridines / administration & dosage
  • Pyridines / adverse effects*
  • Pyrrolidines / administration & dosage
  • Pyrrolidines / adverse effects*
  • Retrospective Studies
  • Salvage Therapy / adverse effects*
  • Salvage Therapy / methods
  • Sarcopenia / diagnosis
  • Sarcopenia / epidemiology*
  • Sarcopenia / etiology
  • Severity of Illness Index
  • Survival Rate
  • Thymine
  • Tomography, X-Ray Computed
  • Trifluridine / administration & dosage
  • Trifluridine / adverse effects*
  • Uracil / administration & dosage
  • Uracil / adverse effects
  • Uracil / analogs & derivatives*

Substances

  • Drug Combinations
  • Phenylurea Compounds
  • Pyridines
  • Pyrrolidines
  • trifluridine tipiracil drug combination
  • regorafenib
  • Uracil
  • Thymine
  • Trifluridine