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

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Summary

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 (cm2/m2). Dose-limiting toxicity (DLT) corresponded to toxicities occurring during the 1st 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 cm2/m2 (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 cm2/m2 (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.

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Acknowledgments

The authors express their gratitude to Lorna Saint Ange for editing.

Funding

This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Disclosure

The authors have declared no conflicts of interest.

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Authors and Affiliations

  1. Phase I Department, Gustave Roussy, Villejuif, France

    Sophie Cousin, A. Hollebecque, O. Mir, A. Varga & J. C. Soria

  2. Department of Biostatistics and Epidemiology, Gustave Roussy, Villejuif, France

    S. Koscielny

  3. Department of Oncology, Cross Cancer Institute, Edmonton, Canada

    V. E. Baracos

  4. Department of Ambulatory Care, Gustave Roussy, Villejuif, France

    S. Antoun

  5. Department of Medical Oncology, Centre Oscar Lambret, 3, rue Frédéric Combemale, 59000, Lille, France

    Sophie Cousin

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  1. Sophie Cousin
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Correspondence to Sophie Cousin.

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Cousin, S., Hollebecque, A., Koscielny, S. et al. Low skeletal muscle is associated with toxicity in patients included in phase I trials. Invest New Drugs 32, 382–387 (2014). https://doi.org/10.1007/s10637-013-0053-6

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  • DOI: https://doi.org/10.1007/s10637-013-0053-6

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