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 evaluate the therapeutic effects of sorafenib and liposome doxorubicin on poorly differentiated thyroid carcinoma (PDTC) xenografts in nude mice.

METHODSSorafenib and liposome doxorubicin were applied to PDTC xenografts in nude mice. The mice were randomized into seven groups: blank control (A), vehicle control (B), single liposome doxorubicin (C), single sorafenib group (D), liposome doxorubicin combined with low dose sorafenib group (E), combined group with medium dosage of sorafenib (F), combined group with high-dose of sorafenib(G). The volume, weight and growth inhibition rate of tumours were measured to evaluate the therapeutic effects of drugs.

RESULTSSorafenib and liposome doxorubicin showed significant antitumor activity in the PDTC xenografts. The mean tumor volumes of seven groups were (1274.13 ± 393.76) mm(3), (1060.00 ± 469.05) mm(3), (726.76 ± 488.22) mm(3), (451.54 ± 97.75) mm(3), (518.37 ± 164.44) mm(3), (310.51 ± 210.53) mm(3), and (228.44 ± 129.21) mm(3), respectively. The mean tumor weights of the seven groups were (1.13 ± 0.42)g, (0.91 ± 0.39)g, (0.78 ± 0.45)g, (0.55 ± 0.17) g, (0.52 ± 0.19) g, (0.34 ± 0.21) g, and (0.19 ± 0.09) g separately. The tumor inhibition rates of group C to G were 30.8%, 40.8%, 42.3%, 62.9%, 72.6% separately.

CONCLUSIONSSorafenib and liposome doxorubicin, no matter for single agent or in combination, showed significant antitumor activity in the PDTC PDTC xenografts in vivo. The tumour-inhibited effect of single sorafenib is better than that of single liposome doxorubicin. Liposome doxorubicin combined with medium dosage of sorafenib had a better therapeutic effect and less side effects.

Animals ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Doxorubicin ; administration & dosage ; Humans ; Liposomes ; administration & dosage ; Mice ; Mice, Nude ; Niacinamide ; administration & dosage ; analogs & derivatives ; Phenylurea Compounds ; administration & dosage ; Thyroid Neoplasms ; drug therapy ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays

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

OBJECTIVETo explore the safety and efficacy of sorafenib in combination with chemotherapy for the treatment of FLT3 positive acute myeloid leukemia (AML), to highlight the impact of FLT3 mutations and targeting therapy on response of AML.

METHODSThe clinical and laboratory features and the treatment response, especially the safety profile of sorafenib in an acute monocytic leukemia patient with FLT-ITD were reported.

RESULTSThe patient achieved clinical and molecular CR after sorafenib was added to the second course of combination chemotherapy. The side effects of sorafenib were mild and tolerable.

CONCLUSIONThe patient responded well to the combination of sorafenib and standard chemotherapy of AML without significant adverse effects.

Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Benzenesulfonates ; administration & dosage ; Female ; Humans ; Leukemia, Monocytic, Acute ; drug therapy ; genetics ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; Pyridines ; administration & dosage ; fms-Like Tyrosine Kinase 3 ; genetics

OBJECTIVETo study the cardiovascular effect of selective orexin-1 receptor (OX1R) antagonist SB408124 in anesthetized rats and explore the underlying mechanism by using intracerebroventricular (ICV) microinjection combined with immunohistochemical assay.

METHODSThe changes of mean arterial blood pressure (MAP) and heart rate (HR) of male Sprague-Dawley rats were recorded during ICV microinjection of SB408124 with or without pretreatment of atropine methyl nitrate or hexamethonium bromide. Furthermore, tyrosine hydroxylase (TH) immunopositive neurons in the rostral ventrolateral medulla (RVLM) of the rat were detected with immunohistochemical assay after ICV microinjection of SB408124.

RESULTSICV administration of SB408124 resulted in a significant decrease in MAP in anesthetized rats, which was accompanied with a mild decrease in HR. The cardiovascular responses elicited by SB408124 were not abolished by pretreatment of atropine methyl nitrate whereas fully abolished by pretreatment of hexamethonium bromide. The number of TH-immunopositive neurons in rat RVLM were significantly decreased following ICV administration of SB408124.

CONCLUSIONICV microinjection of selective OX1R antagonist SB408124 can cause decreases of MAP and HR mediated by inhibiting sympathetic activity in anesthetized rats.

Animals ; Blood Pressure ; drug effects ; Heart Rate ; drug effects ; Male ; Orexin Receptors ; Phenylurea Compounds ; administration & dosage ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; antagonists & inhibitors ; Receptors, Neuropeptide ; antagonists & inhibitors

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

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

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

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