Abstract
PurposeSorafenib is an effective therapy for advanced hepatocellular carcinoma (HCC). Hand–foot syndrome (HFS) is a serious adverse effect associated with sorafenib therapy. This study aimed to develop an updated clinical prediction tool that allows personalized prediction of HFS following sorafenib initiation.MethodsIndividual participant data from Phase III clinical trial NCT00699374 were used in Cox proportional hazard analysis of the association between pre-treatment clinicopathological data and grade ≥ 3 HFS occurring within the first 365 days of sorafenib treatment for advanced HCC. Multivariable prediction models were developed using stepwise forward inclusion and backward deletion and internally validated using a random forest machine learning approach.ResultsOf 542 patients, 116 (21%) experienced grades ≥ 3 HFS. The prediction tool was optimally defined by sex (male vs female), haemoglobin (< 130 vs ≥ 130 g/L) and bilirubin (< 10 vs 10–20 vs ≥ 20 µmol/L). The prediction tool was able to discriminate subgroups with significantly different risks of grade ≥ 3 HFS (P ≤ 0.001). The high (score = 3 +)-, intermediate (score = 2)- and low (score = 0–1)-risk subgroups had 40%, 27% and 14% probability of developing grade ≥ 3 HFS within the first 365 days of sorafenib treatment, respectively.ConclusionA clinical prediction tool defined by female sex, high haemoglobin and low bilirubin had high discrimination for predicting HFS risk. The tool may enable improved evaluation of personalized risks of HFS for patients with advanced HCC initiating sorafenib.
Highlights
Hepatocellular carcinoma (HCC) accounts for approximately 80–85% of primary liver cancers [1]
Data were available from 542 patients with advanced HCC who received sorafenib therapy
This study developed a clinical prediction tool for sorafenibinduced grade ≥ 3 hand–foot syndrome (HFS) in advanced HCC
Summary
Hepatocellular carcinoma (HCC) accounts for approximately 80–85% of primary liver cancers [1]. Due to the lack of symptoms in early stages, HCC is often left undetected until it progresses to advanced stages, resulting in poor prognosis [2, 3]. Sorafenib is a multi-kinase inhibitor approved for Dermatologic side effects are amongst the most common side effects of sorafenib [4, 5]. Hand–foot syndrome (HFS) of any grade is experienced by approximately 61% of patients [5]. HFS typically develops 2–4 weeks after sorafenib initiation [6] and is characterized by painful erythema, scaling, and ulceration affecting the hand and feet, which can lead to reduced patient quality of life [7, 8]. The development of HFS of grade ≥ 3 is considered a serious adverse effect that may lead to dosage regimen adjustment and/or premature treatment termination [9]
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