Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2018; 24(28): 3155-3162
Published online Jul 28, 2018. doi: 10.3748/wjg.v24.i28.3155
Multikinase inhibitor-associated hand-foot skin reaction as a predictor of outcomes in patients with hepatocellular carcinoma treated with sorafenib
Masanori Ochi, Toshiro Kamoshida, Atsushi Ohkawara, Haruka Ohkawara, Nobushige Kakinoki, Shinji Hirai, Akinori Yanaka
Masanori Ochi, Toshiro Kamoshida, Atsushi Ohkawara, Haruka Ohkawara, Nobushige Kakinoki, Shinji Hirai, Department of Gastroenterology, Hitachi General Hospital, Ibaraki 317-0077, Japan
Akinori Yanaka, Hitachi Medical Education and Research Center, University of Tsukuba, Ibaraki 317-0077, Japan
Author contributions: Ochi M, Kamoshida T, Ohkawara A, Ohkawara H, Kakinoki N, Hirai S and Yanaka A contributed equally to this work; Ochi M and Kamoshida T collected and analyzed the data; Ochi M drafted the manuscript; Kamoshida T designed and supervised the study; Ohkawara A, Ohkawara H, Kakinoki N, Hirai S and Yanaka A offered technical or material support; all authors have read and approved the final version to be published.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of the Hitachi General Hospital.
Informed consent statement: Patients were not required to give informed consent to the study, because the analysis used anonymous data that were obtained after patient agreed to treatment by written consent.
Conflict-of-interest statement: Authors have nothing to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Masanori Ochi, MD, Doctor, Department of Gastroenterology, Hitachi General Hospital, 2-1-1, Jonancho, Ibaraki 317-0077, Japan.
Telephone: +81-294-231111 Fax: +81-294-238351
Received: March 17, 2018
Peer-review started: March 17, 2018
First decision: April 18, 2018
Revised: May 9, 2018
Accepted: June 22, 2018
Article in press: June 22, 2018
Published online: July 28, 2018

To investigate the relationship between the onsets of multikinase inhibitor (MKI)-associated hand-foot skin reaction (HFSR) and prognosis under intervention by pharmacists after the introduction of sorafenib.


We conducted a retrospective study involving 40 patients treated with sorafenib. Intervention by pharmacists began at the time of treatment introduction and continued until the appearance of symptomatic exacerbation or non-permissible adverse reactions. We examined the relationship between MKI-associated HFSR and overall survival (OS) after the initiation of treatment.


The median OS was 10.9 mo in the MKI-associated HFSR group and 3.4 mo in the no HFSR group, showing a significant difference in multivariate analysis. A multivariate analysis of the time to treatment failure indicated that the intervention by pharmacists and MKI-associated HFSR were significant factors. The median cumulative dose and the mean medication possession ratio were significantly higher in the intervention group than in the non-intervention group. A borderline significant difference was observed in terms of OS in this group.


Intervention by pharmacists increased drug adherence. Under increased adherence, MKI-associated HFSR was an advantageous surrogate marker. Intervention by healthcare providers needs to be performed for adequate sorafenib treatment.

Keywords: Hepatocellular carcinoma, Surrogate marker, Multikinase inhibitor-associated hand-foot skin reaction, Sorafenib, Intervention by pharmacists

Core tip: Sorafenib is an oral anticancer drug associated with a high incidence of adverse reactions. However, no studies have evaluated its therapeutic efficacy under improved adherence. A surrogate marker of significant improvement in overall survival under improved adherence in advanced hepatocellular carcinoma patients after the introduction of sorafenib was multikinase inhibitor-associated hand-foot skin reaction. Intervention by healthcare providers, including pharmacists specializing in cancer treatment, has improved patient adherence, contributing to the true response to sorafenib treatment.