Aged ; Antineoplastic Agents ; adverse effects ; Carcinoma, Hepatocellular ; drug therapy ; Hand-Foot Syndrome ; diagnosis ; etiology ; Humans ; Liver Neoplasms ; drug therapy ; Male ; Neoplasms, Multiple Primary ; drug therapy ; Niacinamide ; adverse effects ; analogs & derivatives ; Phenylurea Compounds ; adverse effects

Adult ; Female ; Humans ; Leukemia, Myeloid, Acute ; enzymology ; genetics ; Mutation ; genetics ; Niacinamide ; adverse effects ; analogs & derivatives ; Phenylurea Compounds ; adverse effects ; Tandem Repeat Sequences ; genetics ; Thyroiditis ; chemically induced ; enzymology ; genetics ; fms-Like Tyrosine Kinase 3 ; genetics

Tumor lysis syndrome is rare in hepatocellular carcinoma (HCC), but it has been reported more frequently recently in response to treatments such as transcatheter arterial chemoembolization (TACE), radiofrequency thermal ablation (RFTA), and sorafenib. Tumor lysis syndrome induced by low-dose steroid appears to be very unusual in HCC. We report a patient with hepatitis-C-related liver cirrhosis and HCC in whom tumor lysis syndrome occurred due to low-dose steroid (10 mg of prednisolone). The patient was a 90-year-old male who presented at the emergency room of our hospital with general weakness and poor oral intake. He had started to take prednisolone to treat adrenal insufficiency 2 days previously. Laboratory results revealed hyperuricemia, hyperphosphatemia, and increased creatinine. These abnormalities fulfilled the criteria in the Cairo-Bishop definition of tumor lysis syndrome. Although the patient received adequate hydration, severe metabolic acidosis and acute kidney injury progressed unabated. He finally developed multiple organ failure, and died 3 days after admission. This was a case of tumor lysis syndrome caused by administration of low-dose steroid in a patient with HCC.
Acute Kidney Injury/pathology ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Carcinoma, Hepatocellular/*pathology/therapy ; Chemoembolization, Therapeutic ; Creatinine/blood ; Humans ; Liver Neoplasms/*pathology/*therapy ; Male ; Niacinamide/analogs & derivatives/therapeutic use ; Phenylurea Compounds/therapeutic use ; Steroids/adverse effects/therapeutic use ; Tomography, X-Ray Computed ; Tumor Lysis Syndrome/*diagnosis/drug therapy

Hepatocellular carcinoma (HCC) is a critical global health issue and the third most common cause of cancer-related deaths worldwide. The majority of patients who present HCC are already at an advanced stage and their tumors are unresectable. Sorafenib is a multi-kinase inhibitor of the vascular endothelial growth factor pathway and was recently introduced as a therapy for advanced HCC. Furthermore, studies have shown that oral sorafenib has beneficial effects on survival. However, many patients experience diverse side effects, and some of these are severe. Liver abscess development has not been previously documented to be associated with sorafenib administration in HCC. Here, we report the case of a HCC patient that developed a liver abscess while being treated with sorafenib.
Anti-Bacterial Agents/therapeutic use ; Antineoplastic Agents/adverse effects/*therapeutic use ; Carcinoma, Hepatocellular/*drug therapy/radiography ; Clostridium/isolation & purification ; Clostridium Infections/drug therapy/microbiology ; Humans ; Liver Abscess/etiology/*microbiology ; Liver Neoplasms/*drug therapy/radiography ; Male ; Middle Aged ; Niacinamide/adverse effects/*analogs & derivatives/therapeutic use ; Phenylurea Compounds/adverse effects/*therapeutic use ; Tomography, X-Ray Computed

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

BACKGROUND/AIMS: We investigated the effects of sorafenib monotherapy on advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in a clinical setting. METHODS: In total, 143 consecutive patients with unresectable HCC were treated with sorafenib. Among these patients, 30 patients with advanced HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy. RESULTS: All patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group 1/2, 20/10) and Child-Pugh class A or B (A/B, 17/13). Eleven patients had modified Union for International Cancer Control stage IVA tumors, whereas 19 had stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib monotherapy, three patients (10.0%) had a partial response with PVTT revascularization, and nine (30.0%) had stable disease, with a disease control rate of 33.3%. The median overall survival was 3.1 months (95% confidence interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0 months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most troublesome side effects. CONCLUSIONS: A limited proportion of patients with advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy, although the treatment results in this type of patient is extremely poor. Further studies to predict good responders to personalized therapy are warranted.
Adult ; Aged ; Aged, 80 and over ; Anorexia/chemically induced ; Antineoplastic Agents/adverse effects/*therapeutic use ; Carcinoma, Hepatocellular/*drug therapy/pathology ; Diarrhea/chemically induced ; Disease-Free Survival ; Fatigue/chemically induced ; Female ; Hand-Foot Syndrome/etiology ; Humans ; Kaplan-Meier Estimate ; Liver Neoplasms/*drug therapy/pathology ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Nausea/chemically induced ; Neoplasm Invasiveness ; Niacinamide/adverse effects/*analogs & derivatives/therapeutic use ; Phenylurea Compounds/adverse effects/*therapeutic use ; Portal Vein/*pathology ; Proportional Hazards Models ; Tomography, Spiral Computed ; Venous Thrombosis/*drug therapy/pathology

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

OBJECTIVETo evaluate the effectiveness and toxicity of sorafenib for advanced hepatocellular carcinoma.

METHODSAccording to the Cochrane handbook for systematic review, two reviewers independently completed the whole process of literature search, study selection, data collection, and quality assessment. Seven electric databases(PubMed, Cochrane Library, Embase, Chinese Journal Full-text Database, Chinese Biomedical Literature Database, Chinese Scientific and Technical Journal Database, Chinese Medical Association Digital Periodicals Database) were searched and randomized controlled trials (RCT) of sorafenib in the treatment of advanced hepatocellular carcinoma were collected and analyzed.

RESULTSTwo RCT involving 828 patients were finally included. Compared with placebo, sorafenib significantly extended the overall survival and time to radiologic progression and improved the disease control rate. The main adverse effects were systemic, gastrointestinal, and dermatologic symptoms (grade 1 or 2 in severity), although the incidences were significantly higher in sorafenib groups than in control groups.

CONCLUSIONSorafenib is effective and safe for the treatment of advanced hepatocellular carcinoma.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Benzenesulfonates ; adverse effects ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; Humans ; Liver Neoplasms ; drug therapy ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; Pyridines ; adverse effects ; therapeutic use

OBJECTIVETo evaluate the efficacy and analyze the prognostic factors of sorafenib treatment in patient with unresectable primary hepatocellular carcinoma (HCC).

METHODSDuring the period from December 2005 to March 2009, 50 patients with unresectable primary HCC of Child-Pugh status A were treated with sorafenib (400 mg, Bid). The tumor response was evaluated with CT or MRI imaging every 6 - 8 weeks according to the RECIST criteria. The overall survival (OS) and time to progression (TTP) were defined as the time from administration of sorafenib to the death or the last follow up and were evaluated by Kaplan-Meier method.

RESULTSThere was no PR or CR, but 28 patients (56.0%) achieved stable disease. The median follow up time was 15 months with a median OS of 14 months and median TTP of 4 months. The common adverse events were dermal reaction (68.0%, 34/50), diarrhea (52.0%, 26/50), hypertension (4.0%, 2/50), hair loss (14.0%, 7/50), myelosuppression (16.0%, 8/50), and liver dysfunction (20.0%, 10/50). However, most of the drug-related adverse events were grade I-II and reversible. The patients with lower tumor burden and without distant metastasis had better prognosis.

CONCLUSIONSoafenib is effective for unresectable primary HCC with tolerable toxicity. Tumor stage is a predominant prognostic factor.

Adult ; Aged ; Alopecia ; chemically induced ; Antineoplastic Agents ; adverse effects ; therapeutic use ; Benzenesulfonates ; adverse effects ; therapeutic use ; Carcinoma, Hepatocellular ; drug therapy ; Chemoembolization, Therapeutic ; methods ; Diarrhea ; chemically induced ; Disease Progression ; Follow-Up Studies ; Humans ; Hypertension ; chemically induced ; Liver Neoplasms ; drug therapy ; Male ; Middle Aged ; Neoplasm Staging ; Niacinamide ; analogs & derivatives ; Phenylurea Compounds ; Pyridines ; adverse effects ; therapeutic use ; Skin Diseases ; chemically induced ; Survival Rate