Safety and effectiveness of sorafenib in Japanese patients with hepatocellular carcinoma in daily medical practice: interim analysis of a prospective postmarketing all-patient surveillance study

Abstract

Background Sorafenib was approved for treatment of unresectable hepatocellular carcinoma (HCC) in Japan in 2009. A prospective postmarketing all-patient surveillance (PMS) study was requested by Japanese authorities to confirm safety and effectiveness of sorafenib in Japanese HCC population. Methods Patients with unresectable HCC treated with sorafenib were followed up for 12 months. Data on patient demographic characteristics, treatment status, clinical outcome, and adverse events (AEs) were collected. Results This interim analysis included 1109 and 1065 patients evaluable for safety and effectiveness, respectively. Most patients (83.4 %) received the recommended initial dose of 400 mg twice daily. After a follow-up of 12-months, 89.8 % had discontinued treatment, most because of AEs (44.5 %) or progression (33.8 %). The most common drug-related adverse events (DRAE) were hand-foot skin reaction (51.4 %), liver dysfunction (26.4 %), diarrhea (25.1 %), and hypertension (21.6 %). The median overall survival (OS) was 348 days [95 % confidence interval (CI) 299-389 days], and the median duration of treatment was 87 days (95 % CI 78-98 days). Multivariate analyses identified baseline prognostic factors for longer OS, including female sex, low Child-Pugh score, Eastern Cooperative Oncology Group performance status 0, tumor stage I/II/III, low aspartate aminotransferase level, high hemoglobin level, hepatitis C and history of surgical resection. Conclusions In general, the safety and effectiveness findings in this PMS were consistent with findings from previous clinical studies. Sorafenib was well tolerated and clinically useful for Japanese patients. Clinical trial registration number: NCT01411436

Beneficial Effect of Maintaining Hepatic Reserve during Chemotherapy on the Outcomes of Patients with Hepatocellular Carcinoma

“…Our recent study of patients with Child-Pugh B found that an improved Child-Pugh score during chemotherapy is a favorable prognostic factor [7], which is reasonable because hepatic failure is often fatal. In contrast, HAIC and sorafenib are well-tolerated by patients with sufficient hepatic reserve [12,13], and in the present study there were only 3 patients whose Child-Pugh scores rose to ≥9 after 4 weeks of treatment and 2 patients due to liver failure, suggesting that this result was not caused by lethal hepatic failure. Although we did not definitively identify the reason for these findings, the duration of survival after sorafenib treatment contributes to patients' OS [14], in part, because of increased availability of further treatment options [15,16].…”

Serum HMGB1 concentrations at 4 weeks is a useful predictor of extreme poor prognosis for advanced hepatocellular carcinoma treated with sorafenib and hepatic arterial infusion chemotherapy

“…The median survival time (MST) is 40 and 17 months among complete and partial responders, respectively [6][7][8][9][10][11][12][13]. Several studies show the effectiveness of sorafenib in Japanese patients [14,15]. However, not all HCC patients respond to these treatments.…”

Genetic basis of hepatitis virus-associated hepatocellular carcinoma: linkage between infection, inflammation, and tumorigenesis

“…It is currently the second leading cause of cancer-related deaths, with an estimated 500,000-600,000 deaths/year [1][2][3]. To date, multidisciplinary strategies for HCC treatment include surgery, radiofrequency ablation, transarterial chemoembolization, and molecular targeting therapy [4][5][6][7][8][9]. The multi-centric manner of tumorigenesis that is characteristic of HCC development, however, makes it extremely difficult to achieve curative therapy for HCC.…”