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
Research background

A surrogate marker that reflects a better prognosis after the introduction of sorafenib has not yet been established.

Research motivation

The incidence of adverse events after sorafenib introduction is high, reducing drug adherence.

Research objectives

The authors performed intervention by pharmacists using the double-check system to improve drug adherence. In addition, they evaluated a surrogate marker reflecting a better prognosis after sorafenib introduction under increased adherence.

Research methods

This retrospective study was conducted on advanced hepatocellular carcinoma patients who had been treated with sorafenib between May 2009 and March 2017. Establishing the overall survival (OS) as a primary endpoint, the authors evaluated a surrogate marker using multivariate analysis. Furthermore, the effects of intervention by pharmacists on drug adherence were assessed using the time to treatment failure (TTF), median cumulative dose, and medication possession ratio (MPR).

Research results

The subjects were 40 patients who had undergone sorafenib therapy. In the presence of grade 1 or higher multikinase inhibitor (MKI)-associated hand-foot skin reaction (HFSR), OS was significantly prolonged. The results of multivariate analysis showed that the presence of MKI-associated HFSR (hazard ratio = 0.241, 95%CI: 0.102-0.567; P = 0.001) was one of the significant predictive factors for the prolongation of OS. There were significant differences in the TTF, median cumulative dose, and MPR between the intervention and non-intervention groups.

Research conclusions

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

Research perspectives

It remains to be clarified whether intervention by healthcare providers improves the prognosis of hepatocellular carcinoma patients after sorafenib introduction. Therefore, the double-check system should be further improved, and a larger number of patients should be evaluated. Furthermore, a prospective study should be conducted.