There have been recent advances in the treatment of hepatocellular carcinoma (HCC). There has been a clear change in the presentation of HCC, with an increased detection of tumors <2 cm in diameter as result of surveillance programs. In addition, the development of effective local treatment methods has led to the necessity for the selection of base therapeutic modalities on each patient's characteristics. New promising image-guided therapies and new drugs, such as sorafenib, may address the enormous need for expanded treatment options for patients with HCC. Tailored therapies are needed to improve the treatment response and, ultimately, patient survival. Here, we review these advances in the management of HCC.
Carcinoma, Hepatocellular ; Humans ; Niacinamide ; Phenylurea Compounds

Humans ; Leukemia, Myeloid, Acute ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds

Sorafenib is a multi-targeted kinase inhibitor, which is the current standard treatment for advanced hepatocellular carcinoma (HCC). Only one case of radiation recall dermatitis (RRD) associated with sorafenib has been reported so far. Our patient with recurrent HCC was treated with palliative radiotherapy (RT) for the chest wall mass. Sorafenib at 400 mg twice daily was begun on the day following RT. On the 14th day post-RT, an erythematous patch was observed on right chest wall which matched area previously irradiated. It was consistent with RRD. Ten days later, a disseminated exanthematous rash and severe pruritus occurred. Sorafenib was stopped and an oral antihistamine was prescribed to relieve symptoms. At the 1-week follow-up after the cessation of sorafenib, all symptoms were resolved. Physicians should be alert to this recall phenomenon as it can occur both in the skin and elsewhere and the occurrence of RRD may be unpredictable.
Carcinoma, Hepatocellular ; Exanthema ; Follow-Up Studies ; Humans ; Niacinamide ; Phenylurea Compounds ; Phosphotransferases ; Pruritus ; Radiodermatitis ; Skin ; Thoracic Wall

Sorafenib is an oral multikinase inhibitor that has shown a survival benefit in patients with advanced hepatocellular carcinoma, and is considered to be generally safe. We treated a patient with interstitial lung disease that was associated with sorafenib therapy for the treatment of advanced hepatocellular carcinoma. A 74-year-old man with hepatitis-C-virus-related hepatocellular carcinoma was treated with sorafenib. After 8 days of sorafenib administration, he received radiation therapy for an intrahepatic tumor located in segment eight. On the 24th day of sorafenib treatment, the patient developed acute interstitial pneumonitis that rapidly improved after the discontinuation of sorafenib and treatment with high-dose steroids. This case alerts physicians to the possibility of sorafenib-induced interstitial lung disease.
Aged ; Carcinoma, Hepatocellular ; Humans ; Lung Diseases, Interstitial ; Niacinamide ; Phenylurea Compounds ; Steroids

Treatment with sorafenib prolongs both the median survival and time to progression by nearly 3 months in patients with advanced hepatocellular carcinoma. Although the effects of combining sorafenib therapy with other anticancer treatment modalities have not been clarified, combination treatment is strongly expected to be beneficial. We report the case of a 50-year-old man who exhibited a partial response and portal vein thrombosis (PVT) revascularization after sorafenib combined with hepatic arterial infusion chemotherapy (HAIC). He exhibited a decrease in tumor size and PVT after 2 months of sorafenib monotherapy. However, no additional response was seen during the subsequent 2 months. To achieve a better tumor response, we combined HAIC with sorafenib. Daily cisplatin (7 mg/m2 on days 1-5) and 5-fluorouracil (170 mg/m2 on days 1-5) were infused repeatedly every 4 weeks, and the sorafenib prescription was modified. After four cycles of combined therapy, both the tumor size and PVT were much improved and exhibited partial response.
Carcinoma, Hepatocellular ; Cisplatin ; Fluorouracil ; Humans ; Middle Aged ; Niacinamide ; Phenylurea Compounds ; Portal Vein ; Prescriptions ; Thrombosis

Antineoplastic Combined Chemotherapy Protocols ; Humans ; Leukemia, Myeloid, Acute ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds

Sorafenib, as the first approved molecularly targeted agent for hepatocellular carcinoma (HCC), has changed the treatment paradigm for patients with advanced HCC. Although a significant survival advantage has been achieved with sorafenib, the prolongation of survival is modest, even in the cases of Child-Pugh class A. Because of primary resistance and secondary resistance, the anti-tumor effects of sorafenib are limited in a portion of HCC patients. To overcome these limitations of sorafenib, various molecularly targeted therapies have been studied alone or in combination with each other, and also adjuvant to other modalities. The role of sorafenib as an adjuvant or neo-adjuvant therapy needs to be evaluated before and after surgery and locoregional therapies. Because patients with HCC are a highly heterogeneous population in terms of molecular pathogenesis and in terms of the natural course of their disease, development of biomarkers of a response before or during sorafenib treatment and development of other molecularly targeted therapies is imperative for selecting prospective good responders. New agents under development target and block VEGF, VEGFR, PDGFR, FGF, FGFR, EGFR, PI3K/Akt/mTOR, IGFR, MEK, c-MET, glypican-3, JAK2, PD1, CTLA-4, etc. The advent of targeted systemic therapies for advanced HCC may have important implications for the future management of patients with advanced HCC, including a need for improved assessment of disease progression, reliable biomarkers for patient selection, and the use of a multidisciplinary approach.
Biomarkers ; Carcinoma, Hepatocellular* ; Disease Progression ; Drug Therapy* ; General Surgery ; Glypicans ; Humans ; Niacinamide ; Patient Selection ; Phenylurea Compounds ; Vascular Endothelial Growth Factor A

This is the first case report to describe a 44-year-old woman with a history of advanced hepatocellular carcinoma who developed toxic epidermal necrolysis (TEN) clinically after taking 400 mg sorafenib (Nexavar(R), BAY 43-9006) and tosufloxacin orally once per day. Both sorafenib and tosufloxacin were eventually discontinued, and the TEN resolved with corticosteroids and supportive treatment. Clinical physicians should be aware of this possible complication so that early interventions can be made.
Adrenal Cortex Hormones ; Adult ; Bays ; Carcinoma, Hepatocellular ; Early Intervention (Education) ; Epidermal Necrolysis, Toxic ; Female ; Fluoroquinolones ; Humans ; Naphthyridines ; Niacinamide ; Phenylurea Compounds

Sorafenib (Nexavar(R), BAY 43-9006) is a new oral multi-targeted tyrosine kinase inhibitor developed to delay disease progression in advanced solid organ malignancies and metastatic melanoma. Among the many reported toxicities attributed to sorafenib, dermatologic events, such as skin rash, acral erythema, alopecia and xerosis are the most frequently observed side effects. Recently, we experienced a case of a 41-year-old man who presented with generalized maculopapular erythematous eruptions, and acral erythema after sorafenib treatment for his metastatic hepatocellular carcinoma. Herein, we report the case and discuss the undesirable side effects of sorafenib.
Adult ; Alopecia ; Bays ; Carcinoma, Hepatocellular ; Disease Progression ; Erythema ; Exanthema ; Humans ; Melanoma ; Niacinamide ; Phenylurea Compounds ; Protein-Tyrosine Kinases

Portal hypertension, as one of the major complications of liver cirrhosis, is a common clinical syndrome characterized by an increased portal pressure and the formation of portal-systemic collaterals. Currently no ideal therapeutic agent has been available for portal hypertension. Sorafenib is an oral tyrosine kinase inhibitor that has been shown to significantly improve blood flow dynamics, inhibit angiogenesis, reduce liver fibrosis and decrease portal pressure in the treatment of portal hypertension. The authors review the progress in the research of sorafenib in the treatment of portal hypertension and the mechanisms of its actions.
Animals ; Humans ; Hypertension, Portal ; drug therapy ; Niacinamide ; analogs & derivatives ; pharmacology ; therapeutic use ; Phenylurea Compounds ; pharmacology ; therapeutic use