β-Hydroxy-β-methyl Butyrate/L-Arginine/L-Glutamine Supplementation for Preventing Hand-Foot Skin Reaction in Sorafenib for Advanced Hepatocellular Carcinoma

Abstract

Background/aim: Sorafenib is standard treatment for advanced hepatocellular carcinoma (HCC). Hand-foot skin reaction (HFSR) is a notorious side-effect of this therapy. This study evaluated prophylactic benefits of an oral nutritional supplement (ONS) on sorafenib-associated HFSR in advanced HCC.

Patients and methods: This was a prospective, single-center, open-label trial arm using combined ONS and sorafenib in patients with unresectable HCC from August 2014 to February 2018. Control patients received sorafenib without ONS from 2011 to 2014. From September 2014, prophylactic ONS containing β-hydroxy-β-methylbutyrate (HMB), L-arginine, and L-glutamine was given. Sorafenib dosage was 400 mg/day for both groups.

Results: Each group comprised 22 men and three women. Age, sex, Child-Pugh score, and clinical stage excluding IV-B did not significantly differ between the groups. HFSR occurred after 2 weeks: 15/25 patients in the control group (60%; HFSR grade 1: 6, grade 2: 7, grade 3: 2) vs. 8/25 in the ONS group (32%; HFSR grade 1: 4, grade 2: 4, grade 3: 0; p=0.047, Pearson's Chi-square test).

Conclusion: Prophylactic HMB, L-arginine and L-glutamine supplementation effectively prevented sorafenib-associated HFSR in patients with advanced HCC.

Keywords: L-arginine; L-glutamine; Sorafenib; hand–foot skin reaction; β-hydroxy-β-methyl butyrate acid.