Ochi M, Kamoshida T, Araki M, Ikegami T. Prolonged survival in patients with hand-foot skin reaction secondary to cooperative sorafenib treatment. World J Gastroenterol 2021; 27(32): 5424-5437 [PMID: 34539142 DOI: 10.3748/wjg.v27.i32.5424]
Corresponding Author of This Article
Masanori Ochi, MD, Doctor, Department of Gastroenterology, Hitachi General Hospital, Chome-1-1 Jonancho, Ibaraki 317–0077, Japan. maochi-tei@umin.ac.jp
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
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: http://creativecommons.org/licenses/by-nc/4.0/
Masanori Ochi, Toshiro Kamoshida, Department of Gastroenterology, Hitachi General Hospital, Ibaraki 317–0077, Japan
Masahiro Araki, Department of Gastroenterology and Hepatology, Ibaraki Prefectural Central Hospital, Ibaraki Cancer Center, Ibaraki 309-1793, Japan
Tadashi Ikegami, Division of Gastroenterology and Hepatology, Tokyo Medical University Ibaraki Medical Center, Ibaraki 309-1793, Japan
Author contributions: Ochi M, Kamoshida T, Araki M, and Ikegami T contributed equally to this work; Ochi M and Kamoshida T collected and analyzed the data; Ochi M and Kamoshida T drafted the manuscript; Ochi M and Kamoshida T designed and supervised the study; Araki M and Ikegami T offered technical or material support; all authors have read and approved the final version to be published.
Institutional review board statement: The study protocol was approved by the ethics committee of each hospital and was performed according to the ethical standards of the 1975 Declaration of Helsinki.
Informed consent statement: Informed consent was obtained using an opt-out option on each facility’s website (see Institution website uniform resource locators).
Conflict-of-interest statement: None of the authors have any conflicts of interest related to the manuscript.
Data sharing statement: The original anonymous dataset is available on request from the corresponding author at maochi-tei@umin.ac.jp.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Masanori Ochi, MD, Doctor, Department of Gastroenterology, Hitachi General Hospital, Chome-1-1 Jonancho, Ibaraki 317–0077, Japan. maochi-tei@umin.ac.jp
Received: April 9, 2021 Peer-review started: April 9, 2021 First decision: May 27, 2021 Revised: June 22, 2021 Accepted: August 10, 2021 Article in press: August 10, 2021 Published online: August 28, 2021
Abstract
BACKGROUND
Sorafenib is an oral drug that prolongs overall survival (OS) in patients with hepatocellular carcinoma. Adverse events, including hand-foot skin reaction (HFSR), lead to permanent sorafenib discontinuation.
AIM
To clarify the association between interventions for adverse events and patient prognosis.
METHODS
We performed a retrospective, multicenter study of patients treated with sorafenib monotherapy between May 2009 and March 2018. We developed a mutual cooperation system that was initiated at the start of sorafenib treatment to effectively manage adverse events. The mutual cooperation system entailed patients receiving consultations during which pharmacists provided accurate information about sorafenib to alleviate the fear and anxiety related to adverse events. We stratified the patients into three groups: Group A, patients without HFSR but with pharmacist intervention; Group B, patients with HFSR and pharmacist interventions unreported to oncologists (nonmutual cooperation system); and Group C, patients with HFSR and pharmacist interventions known to oncologists (mutual cooperation system). OS and time to treatment failure (TTF) were evaluated using the Kaplan-Meier method.
RESULTS
We enrolled 134 patients (Group A, n = 41; Group B, n = 30; Group C, n = 63). The median OS was significantly different between Groups A and C (6.2 vs 13.9 mo, p < 0.01) but not between Groups A and B (6.2 vs 7.7 mo, P = 0.62). Group A vs Group C was an independent OS predictor (HR, 0.41; 95%CI: 0.25-0.66; P < 0.01). In Group B alone, TTF was significantly lower and the nonadherence rate was higher (P < 0.01). In addition, the Spearman’s rank correlation coefficients between OS and TTF in each group were 0.41 (Group A; P < 0.01), 0.13 (Group B; P = 0.51), and 0.58 (Group C; P < 0.01). There was a highly significant correlation between OS and TTF in Group C. However, there was no correlation between OS and TTF in Group B.
CONCLUSION
The mutual cooperation system increased treatment duration and improved prognosis in patients with HFSR. Future prospective studies (e.g., randomized controlled trials) and improved adherence could help prevent OS underestimation.
Core Tip: We investigated the effect of cooperation between oncologists and pharmacists (mutual cooperation system) on the prognosis of patients with advanced hepatocellular carcinoma treated with sorafenib and found that cooperation increased medication adherence. Prolonged adherence was correlated with overall survival and time to treatment failure in patients with sorafenib-related hand-foot skin reactions. Our mutual cooperation system could be used to manage patients treated with various multikinase inhibitors and improve overall survival in studies that use sorafenib as the control drug. Future clinical investigations that include measures to improve medication adherence could eliminate the underestimation of medication efficacy that may otherwise occur due to preventable nonadherence.
