Low skeletal muscle is associated with toxicity in patients included in phase I trials

Invest New Drugs. 2014 Apr;32(2):382-7. doi: 10.1007/s10637-013-0053-6. Epub 2013 Dec 17.

Abstract

Background: Low muscle mass has been associated with chemotherapy toxicity. We conducted this prospective study to evaluate the effects of body composition on the occurrence of toxicity in phase I trials.

Patients and methods: Patients were consecutively enrolled irrespective of the type of tumor or the type of drug. The Skeletal Muscle Index (SMIndex) and visceral and subcutaneous adipose tissue were assessed with computed tomography imaging by measuring cross-sectional areas of the tissues (cm(2)/m(2)). Dose-limiting toxicity (DLT) corresponded to toxicities occurring during the 1(st) cycle that necessitated dose reduction, postponement or interruption of drug administration and severe toxicity events (STE) corresponded to DLT or permanent treatment withdrawal due to toxicity.

Results: 93 patients were evaluated. Ten percent of patients experienced DLT and had a lower SMIndex: 40.8 ± 4.6 vs. 48.1 ± 9.6 cm(2)/m(2) (p = 0.01). STE occurred in 14 % of the patients. The only factor associated with STE was a low SMIndex: 42.4 ± 5.8 vs. 48.4 ± 9.7 cm(2)/m(2) (p = 0.02). STE were observed in 25.5 % of the patients when the SMIndex was below the median value compared to 6.5 % of patients with a high SMIndex (p = 0.02).

Conclusion: Muscle mass is a critical predictor of severe toxicity events in phase I patients, suggesting that sarcopenia may be considered in assessing patients for eligibility of phase-1 studies.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / adverse effects*
  • Body Composition*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Muscle, Skeletal*
  • Neoplasms / drug therapy*
  • Risk Factors
  • Young Adult

Substances

  • Antineoplastic Agents