Probiotics prevent pegylated liposomal doxorubicin-associated hand-foot syndrome and oral mucositis of breast cancer patients following surgery and chemotherapy:a randomized placebo-controlled trial

Zhang Juan; Jie Chen; Boni Ding; Liang Yongping; Haifeng Cai; Hui Chen; Ling Wang; Yuan Le; Jingcheng Shi; Yuhui Wu; Daqing Ma; Wen Ouyang; Yong Cheng; Jianbin Tong

doi:10.1097/JS9.0000000000002147

Probiotics prevent pegylated liposomal doxorubicin-associated hand-foot syndrome and oral mucositis of breast cancer patients following surgery and chemotherapy:a randomized placebo-controlled trial

Int J Surg. 2024 Dec 24. doi: 10.1097/JS9.0000000000002147. Online ahead of print.

Authors

Zhang Juan^{1

2}, Jie Chen^{3

4}, Boni Ding⁵, Liang Yongping^{1

2}, Haifeng Cai², Hui Chen^{1

6}, Ling Wang⁵, Yuan Le^{1

6}, Jingcheng Shi⁷, Yuhui Wu⁸, Daqing Ma⁹, Wen Ouyang^{1

6}, Yong Cheng¹⁰, Jianbin Tong^{1

6}

Affiliations

¹ Department of Anesthesiology, Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
² Department of Breast Surgery, Tangshan People's Hospital, Tangshan, Hebei, China.
³ Center for Experimental Medicine, Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
⁴ Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, P.R. China.
⁵ Department of Breast and Thyroid Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
⁶ Hunan Province Key Laboratory of Brain Homeostasis, Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
⁷ Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, P.R. China.
⁸ Department of Breast Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
⁹ Division of Anaesthetics, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Chelsea and Westminster Hospital, London, UK.
¹⁰ Department of plastic and burns surgery, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen, Guangdong, P.R. China.

PMID: 39715143
DOI: 10.1097/JS9.0000000000002147

Abstract

Background: Hand-foot syndrome (HFS) and oral mucositis (OM) are common adverse events during cancer chemotherapy and can significantly decrease patients' quality of life and chemotherapy adaptation, however, prevention strategies of these complications yet to be established.

Methods: Patients with stage I-III breast cancer, who had surgery and needed pegylated liposomal doxorubicin (PLD)-based adjuvant chemotherapy were screened, recruited and randomly assigned to receive either probiotics or placebo (three capsules, twice/day) treatment during the course of chemotherapy from Nov. 2019 to Aug. 2020. The incidence and severity of PLD related HFS and OM, and patients' quality of life were assessed. Their plasma biomarkers, metabolites and faecal microbiota compositions were measured. And the results were further verified in animal experiments.

Results: Probiotics supplement during PLD treatment significantly decreased the incidence and the severity of HFS and OM (P < 0.001), improved patients' life quality (P < 0.001), increased the relative abundance of intestinal Enterococcus (P = 0.025) and mitigated the changes of seven plasma metabolites. Among these metabolites, the changes of p-Mentha-1,8-dien-7-ol (MDO) (B = - 0.441, P = 0.02) and L-Arginine (B = - 0.586, P = 0.002) were negatively correlated with the occurrence of severe HFS and OM. MDO can partly reproduce the preventive effects of probiotics on PLD-related skin cell proliferating inhibition, DNA damage, and local inflammation in rats.

Conclusion: Probiotics supplement during PLD-based chemotherapy prevents the incidence and severity of HFS and OM, which may be associated with modulating plasma metabolites including the MDO.