Multiple therapeutic modalities are available for hepatocellular carcinoma (HCC) treatment. We aimed to evaluate the trends for HCC treatment in Korea. Recent trends and patterns in treatment modalities were assessed in HCC patients who first registered for the Health Insurance Review Assessment Service between 2008 and 2012. From 2009 to 2012, 57,690 patients were diagnosed with HCC. Transcatheter arterial chemoembolization (TACE) was the most common treatment modality for initial treatment. Curative treatment modalities like hepatic resection, liver transplantation, and local ablation therapy increased gradually. The 3 most common treatment modalities (hepatic resection, local ablation therapy, TACE) used after initial treatment in 2009 were studied. Following initial hepatic resection, 44.5% of patients required re-treatment. TACE was the most common modality (in 48.3% of cases), while 15.0% of patients received local ablation therapy. After local ablation therapy, 55.4% of patients were re-treated, wherein 45.0% of patients received TACE and 31.5% received local ablation therapy. Following initial TACE, 73.9% patients were re-treated, most commonly with TACE (57.7%) followed by local ablation therapy (12.8%). While there were no significant differences between the initial and re-treatment modalities, various multiple treatments followed the initial treatment. The treatment modalities were interchangeable.
Aged ; Carcinoma, Hepatocellular/epidemiology/pathology/*therapy ; Chemoembolization, Therapeutic ; Combined Modality Therapy/trends ; Cross-Sectional Studies ; Databases, Factual ; Female ; Humans ; Insurance Claim Review ; Liver Neoplasms/epidemiology/pathology/*therapy ; Liver Transplantation ; Male ; Middle Aged ; Niacinamide/administration & dosage/analogs & derivatives ; Phenylurea Compounds/administration & dosage ; Prevalence ; Protein Kinase Inhibitors/administration & dosage ; Republic of Korea/epidemiology

We report a case of regression of multiple pulmonary metastases, which originated from hepatocellular carcinoma after treatment with intravenous administration of high-dose vitamin C. A 74-year-old woman presented to the clinic for her cancer-related symptoms such as general weakness and anorexia. After undergoing initial transarterial chemoembolization (TACE), local recurrence with multiple pulmonary metastases was found. She refused further conventional therapy, including sorafenib tosylate (Nexavar). She did receive high doses of vitamin C (70 g), which were administered into a peripheral vein twice a week for 10 months, and multiple pulmonary metastases were observed to have completely regressed. She then underwent subsequent TACE, resulting in remission of her primary hepatocellular carcinoma.
Aged ; Antineoplastic Agents/administration & dosage/*therapeutic use ; Ascorbic Acid/*administration & dosage/therapeutic use ; Carcinoma, Hepatocellular/*drug therapy/pathology ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Female ; Humans ; Liver Neoplasms/pathology/*therapy ; Lung Neoplasms/*drug therapy/pathology ; Neoplasm Recurrence, Local ; Niacinamide/analogs & derivatives/therapeutic use ; Phenylurea Compounds/therapeutic use ; Treatment Outcome

Antineoplastic Combined Chemotherapy Protocols ; Arsenicals ; administration & dosage ; Carcinoma, Hepatocellular ; drug therapy ; secondary ; Chemoembolization, Therapeutic ; methods ; Humans ; Liver Neoplasms ; Lung Neoplasms ; drug therapy ; secondary ; Niacinamide ; administration & dosage ; analogs & derivatives ; Oxides ; administration & dosage ; Phenylurea Compounds ; administration & dosage

Despite advances in the treatment of hepatocellular carcinoma (HCC), managing HCC with portal vein thrombosis (PVT) remains challenging. PVT is present in 10-40% of HCC cases at the time of diagnosis and its therapeutic options are very limited. Current guidelines mainly recommend sorafenib for advanced HCC with PVT, but surgery, transarterial chemoemolization, external radiation therapy, radioembolization, transarterial infusion chemotherapy, and combination therapy are also still used. Furthermore, several new emerging therapies such as the administration of immunotherapeutic agents and oncolytic viruses are under investigation. This comprehensive literature review presents current and future management options with their relative advantages and disadvantages and summary data on overall survival.
Carcinoma, Hepatocellular/complications/*pathology/therapy ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Humans ; Liver Neoplasms/complications/*pathology/therapy ; Niacinamide/administration & dosage/analogs & derivatives ; Phenylurea Compounds/administration & dosage ; Portal Vein ; Protein Kinase Inhibitors/administration & dosage ; Venous Thrombosis/complications/*pathology

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The only curative treatment modalities for HCC are surgery, percutaneous ablation, and liver transplantation. Unfortunately, the majority of patients have unresectable disease at diagnosis. Therefore, effective treatment options are needed for patients with advanced HCC. The current standard treatment for patients with advanced HCC, according to the Barcelona Clinic Liver Cancer staging system, is the multikinase inhibitor sorafenib. Other alternative therapies are required, due to the limited treatment response to, and tolerance of, this molecular target agent. Clinical trials of hepatic artery infusion chemotherapy, radioembolization, and multimodal treatments have shown favorable results in advanced HCC patients. This article introduces new treatment modalities for advanced HCC and discusses future therapeutic possibilities.
Antineoplastic Agents/administration & dosage/*therapeutic use ; Carcinoma, Hepatocellular/enzymology/pathology/*therapy ; Combined Modality Therapy ; Embolization, Therapeutic/*methods ; Hepatic Artery ; Humans ; Infusions, Intra-Arterial ; Liver Neoplasms/enzymology/pathology/*therapy ; Molecular Targeted Therapy ; Niacinamide/analogs & derivatives/therapeutic use ; Phenylurea Compounds/therapeutic use ; Protein Kinase Inhibitors/therapeutic use ; Radiopharmaceuticals/therapeutic use ; Signal Transduction/drug effects ; Treatment Outcome

OBJECTIVETo explore the efficacy and safty of sorafenib in Child-Pugh class B to class C hepatocellular carcinoma (HCC).

METHODSIn this three-center open-label study from November 2011 to May 2013, we randomly assigned 189 patients with advanced Child-Pugh class B or C HCC patients into two groups, one group with 95 patient to receive sorafenib (400 mg a time, twice a day) and the other group with 94 patients to receive best supportive care. The primary end points were progression-free survival and overall survival.

RESULTSThe median progression-free survival was 2.2 months and 1.9 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.55; 95% confidence interval, 0.40-0.75; P=0.002). The median overall survival was 4.0 months and 3.5 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.48; 95% confidence interval, 0.35-0.68; P<0.001). The main adverse effect of sorafenib was rash and acne of the skin (in 51.7% patients). The incidences of severe rash, diarrhea, and dry skin were 5.6%, 5.6%, and 2.2% in the sorafenib group. One patient reached partial response in the sorafenib group.

CONCLUSIONSSorafenib is safe in patients with liver function impaired advanced HCC. It is effective in terms of progression-free survival and overall survival compared with best supportive care. Liver functions are the important predictive factors.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; mortality ; pathology ; Cross-Over Studies ; Disease-Free Survival ; Female ; Humans ; Kaplan-Meier Estimate ; Liver Function Tests ; Liver Neoplasms ; drug therapy ; mortality ; pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; Neoplasm Staging ; Niacinamide ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Phenylurea Compounds ; administration & dosage ; adverse effects ; therapeutic use ; Treatment Outcome ; Young Adult

PURPOSE: Sorafenib is an effective systemic agent for advanced hepatocellular carcinoma. To increase its efficacy, we evaluated the feasibility and benefit of sorafenib combined with radiotherapy. MATERIALS AND METHODS: From July 2007 to July 2011, 31 patients were treated with a daily dose of 800 mg of sorafenib and radiotherapy. Among them, 13 patients who received radiotherapy on the bone metastasis were excluded. Thirteen patients received 30-54 Gy of radiotherapy on the primary tumor (primary group) and 5 patients received 30-58.4 Gy on the measurable metastatic lesions (measurable metastasis group). Tumor responses at 1 month after the completion of radiotherapy and overall survival were evaluated. RESULTS: The in-field response rate was 100% in the primary group and 60% in the measurable metastasis group. A decrease of more than 80% in the tumor marker alpha-fetoprotein was observed in 7 patients in the primary group (54%). Toxicities of grades 3-4 were hand-foot syndrome in 3 (17%) patients, duodenal bleeding in 1 (6%) patient, thrombocytopenia in 3 (17%) patients and elevation of aspartate transaminase in 1 (6%) patient. The median overall survival was 7.8 months (95% confidence interval, 3.0-12.6). CONCLUSION: The combined treatment of sorafenib and radiotherapy was feasible and induced substantial tumor responses in the target lesions. The results of this study emphasize the importance of individualized approach in the management of advanced hepatocellular carcinoma and encourage the initiation of a controlled clinical trial.
Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use ; Carcinoma, Hepatocellular/drug therapy/pathology/*radiotherapy ; Chemotherapy, Adjuvant ; Feasibility Studies ; Female ; Humans ; Liver Neoplasms/drug therapy/pathology/*radiotherapy ; Male ; Niacinamide/administration & dosage/adverse effects/*analogs & derivatives/therapeutic use ; Phenylurea Compounds/administration & dosage/adverse effects/*therapeutic use ; Radiation Dosage ; Radiotherapy/adverse effects

Alpha-fetoprotein-Producing gastric cancer is associated with poor prognosis because of frequent liver and lymph node metastasis. We present a case with synchronous liver metastasis who survived for 5 years. A 69-year-old man with upper abdominal pain was referred to our hospital. Gastrointestinal endoscopy revealed a Borrmann II-like tumor in the lower part of the stomach. Computed tomography revealed a tumor in the left lobe of the liver. Serum alpha-fetoprotein levels were markedly increased. We performed distal gastrectomy after administering oral tegafur/gimeracil/oteracil potassium and administered hepatic intra-arterial cisplatin injection. Liver metastasis showed partial response on computed tomography. Despite left hepatic lobectomy, further metastases to the liver and mediastinal lymph nodes became difficult to control. After sorafenib tosylate administration, stabilization of the disease was observed for 4 months. We conclude that hepatic intra-arterial chemotherapy and oral administration of sorafenib tosylate may potentially improve the prognosis in such cases.
Abdominal Pain ; Administration, Oral ; alpha-Fetoproteins ; Cisplatin ; Endoscopy, Gastrointestinal ; Gastrectomy ; Liver ; Lymph Nodes ; Neoplasm Metastasis ; Niacinamide ; Phenylurea Compounds ; Potassium ; Prognosis ; Stomach ; Stomach Neoplasms

OBJECTIVETo investigate the clinic predictors of efficacy and adverse events of sorafenib in treating with advanced hepatocellular carcinoma (HCC) patients.

METHODSFrom December 2008 to October 2011, 54 patients received sorafenib for unresectable or metastatic HCC. There were 46 male and 8 female patients. The mean age was 48.7 years (ranging from 21 to 77 years). Patients received sorafenib orally 400 mg twice daily on a continuous dosing schedule with 6 weeks counting as a single cycle. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumor and toxicity grading was performed using the National Cancer Institute Common Toxicity Criteria version 3.0. The relationship between different clinic variable factors and curative effects of sorafenib was analyzed by using Cox proportion hazard regression analysis.

RESULTSHCC was etiological related to HBV in 52 patients (96.3%). Following sorafenib therapy, 2 patients (3.7%) achieved a partial response and 24 patients (44.4%) achieved stable disease, with a disease control rate of 48.1%. The median time to progression (TTP) was 3.8 months. Multivariate analysis showed that greater Child and Eastern Cooperative Oncology Group (ECOG) grade were independent predictors of shorter TTP (HR = 1.361, 95%CI: 1.081 - 12.665, P = 0.041; HR = 1.449, 95%CI: 1.151 - 12.305, P = 0.032). The common adverse events were hand-foot syndrome (64.8%), alopecia (46.3%), and diarrhea (44.4%).

CONCLUSIONSSingle-agent sorafenib demonstrates good efficacy and acceptable tolerability in treating advanced HCC. The presents of Child class A and ECOG performance grade 0 predict better response to sorafenib in advanced HCC patients.

Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; Female ; Humans ; Liver Neoplasms ; drug therapy ; Male ; Middle Aged ; Niacinamide ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Phenylurea Compounds ; administration & dosage ; adverse effects ; therapeutic use ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVETo evaluate the therapeutic efficacy of sorafenib in combination with microwave coagulation therapy (MCT) and trans-arterial chemoembolization (TACE) in patients with recurrent liver cancer.

METHODSFrom January 2006 to January 2010, 90 patients with recurrent hepatocellular carcinoma (HCC) were treated with MCT and TACE in our hospital. The treatment group received sorafenib + MCT + TACE, and the control group received MCT + TACE.

RESULTSRR of the treatment group was 66.7%, which of the control group was 52.0% (P > 0.05). DCR was 83.3% in the treatment group and 64.5% in the control group (P < 0.05). Through a comparison of survival curves along with the extension of time, the survival rates of the two groups were decreased, but the treatment group (group 1) had a significantly higher one than the control group (group 2), with a statistically significant difference (P < 0.05).

CONCLUSIONSorafenib combined with MCT and TACE can improve the disease control rate and prolong the survival in patients with recurrent HCC.

Adult ; Aged ; Antineoplastic Agents ; therapeutic use ; Carboplatin ; administration & dosage ; Carcinoma, Hepatocellular ; drug therapy ; surgery ; therapy ; Catheter Ablation ; methods ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Doxorubicin ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Follow-Up Studies ; Humans ; Iodized Oil ; administration & dosage ; Liver Neoplasms ; drug therapy ; surgery ; therapy ; Male ; Microwaves ; therapeutic use ; Middle Aged ; Neoplasm Recurrence, Local ; Niacinamide ; analogs & derivatives ; therapeutic use ; Phenylurea Compounds ; therapeutic use ; Protein Kinase Inhibitors ; therapeutic use ; Remission Induction ; Survival Rate