<p>Severe Fatigue is an Important Factor in the Prognosis of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib</p>

Abstract

Objective: To investigate the effects of fatigue on the survival of patients with advanced hepatocellular carcinoma treated with sorafenib. Patients and Methods: A retrospective analysis of 182 cases of patients with advanced hepatocellular carcinoma treated with sorafenib in our hospital from October 1, 2008, to October 31, 2017, showed clinical and pathological data and follow-up results. The clinical and pathological data as well as follow-up results of 182 patients with advanced hepatocellular carcinoma treated with sorafenib in our hospital from October 1, 2008, to October 31, 2018, were retrospectively analyzed. All patients were treated for at least 3 months. Patients were divided into three groups: fatigue grade I (n=74), fatigue grade II (n=62), and fatigue grade III (n=46), according to National Cancer Institute common terminology criteria for adverse events (NCI CTCAE) version 5.0. Survival analysis between groups was performed by the Kaplan-Meier method (Log rank test), continuous variables were analyzed by t-test, and categorical variables were analyzed by chi-square test. Results: The overall survival (OS) of patients who were relieved of fatigue was 33.0±9.3 months, whereas the OS of patients who were not relieved of fatigue was 15.0±1.8 months (P<0.000). Furthermore, the time to progress (TTP) of patients who were relieved of fatigue by resting was 20.3 ± 10.9 months compared to a TTP of 7.7 ± 1.0 months in patients who were not relieved of fatigue (P<0.000). Conclusion: Patients, especially the elderly and infirm, were more susceptible to toxicity.

Two important factors affecting the prognosis of patients treated with sorafenib followed by regorafenib for advanced hepatocellular carcinoma

“…Thus, once the fatigue risk factors are determined, the most vulnerable patients require early treatment. 32 …”

“…Thus, once the fatigue risk factors are determined, the most vulnerable patients require early treatment. 32 In this study, after grouping patients according their fatigue level, Kaplan-Meier analysis (log-rank test) was performed, followed by Cox analysis. The median OS times from the start of regorafenib therapy for grades I, II, and III were 12.0, 10.1, and 8.7 months, respectively, illustrating that the duration of survival decreased as the severity of fatigue increased.…”

Diarylureas as Antitumor Agents

“…The efficacy of sorafenib is limited by several factors as systematic tolerance and the poor solubility in Sorafenib inhibits the kinase activity of C-RAF and B-RAF (wild type and V600E mutant) showing IC 50 = 6.22 and 38 nM, respectively. This compound is considered the most important drug in the late stage of injury for advanced stages of HCC [32] which is the second cause of cancer-related mortality all over the world [33]. For more than ten years, sorafenib has been the sole systemic treatment for advanced HCC [34].…”