Prospective Trial of Monocyte Count as a Biomarker of Hand-Foot Syndrome Among Patients With Soft Tissue Sarcomas Treated With Pegylated Liposomal Doxorubicin and Ifosfamide

Keith M Skubitz; Bruce R Lindgren; Evidio Domingo-Musibay; Edward Y Cheng

doi:10.7759/cureus.24498

Prospective Trial of Monocyte Count as a Biomarker of Hand-Foot Syndrome Among Patients With Soft Tissue Sarcomas Treated With Pegylated Liposomal Doxorubicin and Ifosfamide

Cureus. 2022 Apr 26;14(4):e24498. doi: 10.7759/cureus.24498. eCollection 2022 Apr.

Authors

Keith M Skubitz^{1

2}, Bruce R Lindgren², Evidio Domingo-Musibay^{1

2}, Edward Y Cheng^{3

2}

Affiliations

¹ Medicine, University of Minnesota, Minneapolis, USA.
² Masonic Cancer Center, University of Minnesota, Minneapolis, USA.
³ Orthopaedics, University of Minnesota, Minneapolis, USA.

Abstract

Pegylated liposomal doxorubicin (PLD) is widely used and can be used for prolonged periods, with the limiting toxicity usually being hand-foot syndrome (HFS). The pharmacokinetics of PLD is variable between patients, leading to variability in the risk of developing HFS. Dosing based on body surface area does not decrease variability in PLD clearance; thus, other predictive markers could be useful. The peripheral blood absolute monocyte count (AMC) has been suggested as a possible marker of both reticuloendothelial system function and PLD pharmacokinetics. The present study examined the AMC as a potential predictive biomarker in a prospective trial of pre-operative PLD combined with ifosfamide in soft tissue sarcomas (STSs). While our results suggest a relationship between pre-treatment AMC and PLD-induced HFS, the association did not reach statistical significance. The clinical utility of the AMC as a predictor of PLD-induced HFS appears limited, at least when given with ifosfamide.

Keywords: doxorubicin; drug-related side effect; hand-foot syndrome; liposome; monocyte; pegylated-liposomal doxorubicin; pharmacokinetics; sarcoma; toxicity.

Grants and funding

We would like to thank Kevin Franklin, James Dinnerstein, James Swenson's families, and the Karen Wyckoff Rein in Sarcoma Foundation for research support. Research reported in this publication was supported by NIH grant P30CA077598 utilizing the Biostatistics and Bioinformatics Core shared resource of the Masonic Cancer Center, University of Minnesota, and the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1-TR002494. The content is solely the authors' responsibility and does not necessarily represent the official views of the National Institutes of Health. The authors declare no conflicts of interest in preparing this article.