Real-Life Clinical Practice with Sorafenib in Advanced Hepatocellular Carcinoma: A Single-Center Experience Second Analysis

Abstract

Objectives: Sorafenib has become a standard therapy for advanced hepatocellular carcinoma following the demonstration of significant increase in progression-free survival as well as overall survival (OS) in the 2-phase III trials. We examined efficacy and adverse events (AEs) in patients treated with sorafenib over a 6-year period since approval in Japan. Methods: Two hundred and forty-one patients treated with sorafenib at the Kinki University Hospital were retrospectively analyzed clinically for the factors related to survival periods, tumor response evaluated by the Response Evaluation Criteria In Cancer of the Liver (RECICL) and AEs. Results: OS was 14.3 months. According to the RECICL, the objective response and disease control rates were 18.6% (43 of 241) and 61.1% (137 of 241), respectively. AEs were seen in 77.3% (187 of 241), with Grade 3 or higher in 23.6% (57 of 241). The most frequent AE was hand-foot skin reaction in 109 patients (45.0%), and 28 patients (11.8%) showed Grade 3 or higher. Significant factors contributing to the OS were treatment duration (p = 0.0204), up-to-7 criteria (p = 0.0400), increase of Child-Pugh score (p = 0.0008) and tumor response determined by the RECICL (p = 0.0007). Conclusion: Based on the analysis, using many cases at a single center, we concluded that continuation of treatment with sorafenib for ≥90 days without decrease of liver function was critical if tumor response was determined as stable disease or higher.

Muscle volume loss as a prognostic marker in hepatocellular carcinoma patients treated with sorafenib

“…In the present muscle‐atrophy group, muscle wasting after starting sorafenib might have more frequently caused fatigue, asthenia, and physical disability compared to the non‐atrophy group, and resultant physical changes may disturb continuation of sorafenib therapy, eventually leading to a worse prognosis. Recently, a long duration of sorafenib treatment has been reported to be an important prognostic factor for overall survival . Of course, it is important to manage adverse events of sorafenib for a long duration of treatment.…”

“…Recently, a long duration of sorafenib treatment has been reported to be an important prognostic factor for overall survival. 26,27 Of course, it is important to manage adverse events of sorafenib for a long duration of treatment. In our study, we found no significant differences in regard to the frequency of patients with adverse events, amount of sorafenib within the first 2 months after starting treatment, rate of discontinuing sorafenib, or TTP between the groups.…”

Skeletal muscle mass is associated with toxicity, treatment tolerability, and additional or subsequent therapies in patients with hepatocellular carcinoma receiving sorafenib treatment

“…Regarding the association between treatment duration and survival, two previous studies have demonstrated that the duration of sorafenib treatment is an independent risk factor for survival. 33,34 These findings suggest that skeletal muscle mass seems to be associated with OS when there is no difference in the duration of sorafenib treatment. However, the duration of sorafenib treatment might be more important for OS than skeletal muscle mass if the duration of treatment differs between patients with LSMM and non-LSMM patients.…”

“…The study indicated that presarcopenia is a significant prognostic factor in patients with two or less negative prognostic factors (serum albumin level ≤ 3.5 g/dL, AFP level ≥ 100 ng/mL, the presence of bilateral lesions, or the presence of major portal vein invasion). Regarding the association between treatment duration and survival, two previous studies have demonstrated that the duration of sorafenib treatment is an independent risk factor for survival . These findings suggest that skeletal muscle mass seems to be associated with OS when there is no difference in the duration of sorafenib treatment.…”

Grade III hand-foot skin reaction induced by sorafenib

“…In a Japanese study, 45.0% of 241 patients diagnosed with advanced hepatocellular carcinoma developed this syndrome. 2 , 3 …”