The impact of skeletal muscle on the pharmacokinetics and toxicity of 5-fluorouracil in colorectal cancer

Grant R. Williams, Allison M. Deal, Shlomit Strulov Shachar, Christine M. Walko, Jai N. Patel, Bert O’Neil, Howard L. McLeod, Marc S. Weinberg, Seul Ki Choi, Hyman B. Muss, Hanna K. Sanoff

Research output: Contribution to journalArticlepeer-review


Purpose: Great heterogeneity exists in the ability of adults with cancer to tolerate chemotherapy. Variability in body composition may affect rates of metabolism of cytotoxic agents and contribute to the variable chemotherapy toxicity observed. The objective of this exploratory study was to examine the association of low skeletal muscle, commonly known as sarcopenia, on the pharmacokinetics (PKs) of 5-fluorouracil (5FU) in patients receiving FOLFOX for colorectal cancer. Methods: We performed a secondary analysis of a completed multicenter trial that investigated PK-guided 5FU dosing in patients receiving mFOLFOX6 +/− bevacizumab for colorectal cancer. Cycle 1 PK samples were obtained 2–44 h after the start of the 5FU infusion (steady state). Results: No significant differences in first cycle 5FU area-under-the-concentration-time-curve (AUC) were found between sarcopenic and non-sarcopenic patients (17.3 vs. 19.3 AUC, p = 0.43). Patients with grade 3/4 toxicity had a higher dose of 5FU per kg lean body mass (LBM) (105 vs. 93 mg/kg, p = 0.06), most notably for hematological toxicities (110 vs. 94 mg/kg, p = 0.002); however, no correlation between the dose/LBM and 5FU AUC was found. Conclusions: Although our results did not confirm the impact of low skeletal muscle on PKs of 5FU, further research exploring the impact of body composition on chemotherapy PKs and related toxicities is warranted with the potential for alternative dosing strategies in sarcopenic patients to reduce unnecessary toxicities while maintaining efficacy.

Original languageEnglish
Pages (from-to)413-417
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Issue number2
StatePublished - 1 Feb 2018
Externally publishedYes


  • Cancer
  • Pharmacokinetics
  • Sarcopenia
  • Skeletal muscle index

All Science Journal Classification (ASJC) codes

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)


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