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1.
J Hepatol ; 70(4): 684-691, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30529387

RESUMEN

BACKGROUND & AIMS: Sorafenib is first-line standard of care for patients with advanced hepatocellular carcinoma (HCC), yet it confers limited survival benefit. Therefore, we aimed to compare clinical outcomes of sorafenib combined with concurrent conventional transarterial chemoembolization (cTACE) vs. sorafenib alone in patients with advanced HCC. METHODS: In this investigator-initiated, multicenter, phase III trial, patients were randomized to receive sorafenib alone (Arm S, n = 169) or in combination with cTACE on demand (Arm C, n = 170). Sorafenib was started within 3 days and cTACE within 7-21 days of randomization. The primary endpoint was overall survival (OS). RESULTS: For Arms C and S, the median OS was 12.8 vs. 10.8 months (hazard ratio [HR] 0.91; 90% CI 0.69-1.21; p = 0.290); median time to progression, 5.3 vs. 3.5 months (HR 0.67; 90% CI 0.53-0.85; p = 0.003); median progression-free survival, 5.2 vs. 3.6 months (HR 0.73; 90% CI 0.59-0.91; p = 0.01); and tumor response rate, 60.6% vs. 47.3% (p = 0.005). For Arms C and S, serious (grade ≥3) adverse events occurred in 33.3% vs. 19.8% (p = 0.006) of patients and included increased alanine aminotransferase levels (20.3% vs. 3.6%), hyperbilirubinemia (11.8% vs. 3.0%), ascites (11.8% vs. 4.2%), thrombocytopenia (7.2% vs. 1.2%), anorexia (7.2% vs. 1.2%), and hand-foot skin reaction (10.5% vs. 11.4%). A post hoc subgroup analysis compared OS in Arm C patients (46.4%) receiving ≥2 cTACE sessions to Arm S patients (18.6 vs. 10.8 months; HR 0.58; 95% CI 0.40-0.82; p = 0.006). CONCLUSION: Compared with sorafenib alone, sorafenib combined with cTACE did not improve OS in patients with advanced HCC. However, sorafenib combined with cTACE significantly improved time to progression, progression-free survival, and tumor response rate. Sorafenib alone remains the first-line standard of care for patients with advanced HCC. LAY SUMMARY: For patients with advanced hepatocellular carcinoma requiring sorafenib therapy, co-administration with conventional transarterial chemoembolization did not improve overall survival compared to sorafenib alone. Therefore, sorafenib alone remains the first-line standard of care for patients with advanced hepatocellular carcinoma. Clinical Trial Number: NCT01829035.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/tratamiento farmacológico , Sorafenib/uso terapéutico , Anciano , Alanina Transaminasa/sangre , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Ascitis/etiología , Quimioembolización Terapéutica/efectos adversos , Terapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Hiperbilirrubinemia/etiología , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Sorafenib/administración & dosificación , Sorafenib/efectos adversos , Trombocitopenia/etiología
2.
Gut ; 68(6): 1065-1075, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30108162

RESUMEN

OBJECTIVE: Sorafenib is the standard systemic therapy for advanced hepatocellular carcinoma (HCC). Survival benefits of resection/local ablation for early HCC are compromised by 70% 5-year recurrence rates. The phase 3 STORM trial comparing sorafenib with placebo as adjuvant treatment did not achieve its primary endpoint of improving recurrence-free survival (RFS). The biomarker companion study BIOSTORM aims to define (A) predictors of recurrence prevention with sorafenib and (B) prognostic factors with B level of evidence. DESIGN: Tumour tissue from 188 patients randomised to receive sorafenib (83) or placebo (105) in the STORM trial was collected. Analyses included gene expression profiling, targeted exome sequencing (19 known oncodrivers), immunohistochemistry (pERK, pVEGFR2, Ki67), fluorescence in situ hybridisation (VEGFA) and immunome. A gene signature capturing improved RFS in sorafenib-treated patients was generated. All 70 RFS events were recurrences, thus time to recurrence equalled RFS. Predictive and prognostic value was assessed using Cox regression models and interaction test. RESULTS: BIOSTORM recapitulates clinicopathological characteristics of STORM. None of the biomarkers tested (related to angiogenesis and proliferation) or previously proposed gene signatures, or mutations predicted sorafenib benefit or recurrence. A newly generated 146-gene signature identifying 30% of patients captured benefit to sorafenib in terms of RFS (p of interaction=0.04). These sorafenib RFS responders were significantly enriched in CD4+ T, B and cytolytic natural killer cells, and lacked activated adaptive immune components. Hepatocytic pERK (HR=2.41; p=0.012) and microvascular invasion (HR=2.09; p=0.017) were independent prognostic factors. CONCLUSION: In BIOSTORM, only hepatocytic pERK and microvascular invasion predicted poor RFS. No mutation, gene amplification or previously proposed gene signatures predicted sorafenib benefit. A newly generated multigene signature associated with improved RFS on sorafenib warrants further validation. TRIAL REGISTRATION NUMBER: NCT00692770.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/patología , Sorafenib/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Inmunohistoquímica , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Terapia Molecular Dirigida/métodos , Invasividad Neoplásica/patología , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Pronóstico , Análisis de Supervivencia , Adhesión del Tejido , Resultado del Tratamiento
3.
Am J Clin Oncol ; 40(2): 167-174, 2017 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25268070

RESUMEN

BACKGROUND: The purpose of this study was to build prognostic models capable of estimating the outcomes of individual sorafenib-treated advanced stage hepatocellular carcinoma (HCC) patients based on specific patient and tumor factors. METHODS: A parametric model for time-to-event data was used to construct scoring systems based on the intent-to-treat data set from 480 sorafenib-treated patients with advanced stage HCC: 356 for derivation and 124 for validation. Clinical parameters included in the models were based on importance variable scores generated by a random forest approach and bootstrap resampling. The model's accuracy was internally and externally assessed using the time-dependent C-index of discrimination and a Hosmer-Lemeshow type test for calibration. RESULTS: The models generated for time-to-progression and overall survival based on Child-Pugh score, serum α-fetoprotein, tumor morphology, and vascular invasion and/or extrahepatic involvement had good calibration and discrimination abilities, with C-indexes of 0.669 (3 mo progression) and 0.809 (6 mo survival), respectively. External validation results also showed that these models performed well in terms of goodness-of-fit and discrimination (C-index: 0.746 for 3 mo progression and 0.875 for 6 mo survival). Receiver operating characteristic curve analysis in the validation patients indicated that these models have better predictive power than Child-Pugh scores (C-index: 0.686 for 3 mo progression and 0.777 for 6 mo survival). CONCLUSIONS: The prognostic tools developed to quantify the potential outcomes for progression and survival expected from sorafenib treatment can serve as useful clinical aids in personalized decision making regarding treatment in advanced stage HCC patients.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Modelos Estadísticos , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Niacinamida/uso terapéutico , Pronóstico , Medición de Riesgo , Sorafenib , Tasa de Supervivencia
4.
Cancer Res Treat ; 48(4): 1243-1252, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26910470

RESUMEN

PURPOSE: The purpose of this study is to report real life experiences of sorafenib therapy for hepatocellular carcinoma (HCC) in Korea, using a subset of data from GIDEON (Global Investigation of Therapeutic Decisions in HCC and of Its Treatment with Sorafenib; a large, prospective, observational study). MATERIALS AND METHODS: Between January 2009 and April 2012, a total of 497 patients were enrolled from 11 sites in Korea. Of these, 482 patients were evaluable for safety analyses. Case report forms of paper or electronic version were used to record safety and efficacy data from all patients. RESULTS: More patients of Child-Pugh A received sorafenib for > 8 weeks than did patients of Child-Pugh B (55.5% vs. 34.3%). Child-Pugh score did not appear to influence the starting dose of sorafenib, and approximately 70% of patients both in Child-Pugh A and B groups received the recommended initial daily dose of 800 mg (69.0% and 69.5%, respectively). The median overall survival (OS) and time to progression (TTP) were 8.5 months and 2.5 months. In Child-Pugh A patients, the median OS and TTP were 10.2 months and 2.5 months. The most frequent treatment-emergent drug-related adverse event was hand-foot skin reaction (31.7%), followed by diarrhea (18.0%). The incidence of treatment-emergent adverse events was similar in both Child-Pugh A (85.4%) and Child-Pugh B (84.8%) patients. CONCLUSION: Sorafenib was well tolerated by Korean HCC patients in clinical settings, and the safety profile did not appear to differ by Child-Pugh status. Survival benefit in Korean patients was in line with that of a previous pivotal phase III trial (SHARP).


Asunto(s)
Carcinoma Hepatocelular/tratamiento farmacológico , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Neoplasias Hepáticas/tratamiento farmacológico , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Adulto , Anciano , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/patología , Supervivencia sin Enfermedad , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/patología , Femenino , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , República de Corea/epidemiología , Sorafenib , Resultado del Tratamiento
5.
Lancet Oncol ; 16(13): 1344-54, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26361969

RESUMEN

BACKGROUND: There is no standard of care for adjuvant therapy for patients with hepatocellular carcinoma. This trial was designed to assess the efficacy and safety of sorafenib versus placebo as adjuvant therapy in patients with hepatocellular carcinoma after surgical resection or local ablation. METHODS: We undertook this phase 3, double-blind, placebo-controlled study of patients with hepatocellular carcinoma with a complete radiological response after surgical resection (n=900) or local ablation (n=214) in 202 sites (hospitals and research centres) in 28 countries. Patients were randomly assigned (1:1) to receive 400 mg oral sorafenib or placebo twice a day, for a maximum of 4 years, according to a block randomisation scheme (block size of four) using an interactive voice-response system. Patients were stratified by curative treatment, geography, Child-Pugh status, and recurrence risk. The primary outcome was recurrence-free survival assessed after database cut-off on Nov 29, 2013. We analysed efficacy in the intention-to-treat population and safety in randomly assigned patients receiving at least one study dose. The final analysis is reported. This study is registered with ClinicalTrials.gov, number NCT00692770. FINDINGS: We screened 1602 patients between Aug 15, 2008, and Nov 17, 2010, and randomly assigned 1114 patients. Of 556 patients in the sorafenib group, 553 (>99%) received the study treatment and 471 (85%) terminated treatment. Of 558 patients in the placebo group, 554 (99%) received the study treatment and 447 (80%) terminated treatment. Median duration of treatment and mean daily dose were 12·5 months (IQR 2·6-35·8) and 577 mg per day (SD 212·8) for sorafenib, compared with 22·2 months (8·1-38·8) and 778·0 mg per day (79·8) for placebo. Dose modification was reported for 497 (89%) of 559 patients in the sorafenib group and 206 (38%) of 548 patients in the placebo group. At final analysis, 464 recurrence-free survival events had occurred (270 in the placebo group and 194 in the sorafenib group). Median follow-up for recurrence-free survival was 8·5 months (IQR 2·9-19·5) in the sorafenib group and 8·4 months (2·9-19·8) in the placebo group. We noted no difference in median recurrence-free survival between the two groups (33·3 months in the sorafenib group vs 33·7 months in the placebo group; hazard ratio [HR] 0·940; 95% CI 0·780-1·134; one-sided p=0·26). The most common grade 3 or 4 adverse events were hand-foot skin reaction (154 [28%] of 559 patients in the sorafenib group vs four [<1%] of 548 patients in the placebo group) and diarrhoea (36 [6%] vs five [<1%] in the placebo group). Sorafenib-related serious adverse events included hand-foot skin reaction (ten [2%]), abnormal hepatic function (four [<1%]), and fatigue (three [<1%]). There were four (<1%) drug-related deaths in the sorafenib group and two (<1%) in the placebo group. INTERPRETATION: Our data indicate that sorafenib is not an effective intervention in the adjuvant setting for hepatocellular carcinoma following resection or ablation.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Ablación por Catéter , Hepatectomía , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Asia , Australia , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Ablación por Catéter/efectos adversos , Ablación por Catéter/mortalidad , Quimioterapia Adyuvante , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Método Doble Ciego , Europa (Continente) , Femenino , Hepatectomía/efectos adversos , Hepatectomía/mortalidad , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Nueva Zelanda , Niacinamida/administración & dosificación , Niacinamida/efectos adversos , Niacinamida/uso terapéutico , América del Norte , Compuestos de Fenilurea/administración & dosificación , Compuestos de Fenilurea/efectos adversos , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/efectos adversos , Factores de Riesgo , Sorafenib , América del Sur , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
6.
J Vasc Interv Radiol ; 26(3): 320-9.e6, 2015 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25612807

RESUMEN

PURPOSE: To compare efficacy of transarterial chemoembolization with and without radiation therapy (RT) versus sorafenib for advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). MATERIALS AND METHODS: This single-center retrospective study involved 557 patients with HCC with PVTT who initially received chemoembolization (1997-2002; n = 295), chemoembolization and RT (2003-2008; n = 196), or sorafenib (2009-2012; n = 66) according to eligibility criteria among an initial population of 617. The three groups were divided into three pairs (chemoembolization vs chemoembolization/RT, chemoembolization vs sorafenib, and chemoembolization/RT vs sorafenib), and time to progression (TTP) and overall survival (OS) were compared by propensity-score analyses. RESULTS: The chemoembolization/RT group had longer median TTP and OS than the chemoembolization-alone and sorafenib groups (P < .001). Multivariate Cox analysis revealed that chemoembolization/RT treatment was an independent predictor of favorable TTP and OS. In the matched cohort, median TTP and OS were significantly longer in the chemoembolization/RT group than the chemoembolization-alone group (102 pairs; TTP, 8.7 mo vs 3.6 mo [P < .001]; OS, 11.4 mo vs 7.4 mo [P = .023]) or the sorafenib group (30 pairs; TTP, 5.1 mo vs 1.6 mo [P < .001]; OS, 8.2 mo vs 3.2 mo [P < .001]), in agreement with the inverse probability of treatment weighted (IPTW) outcomes. In matching analyses, the chemoembolization-alone group had longer median TTP and OS than the sorafenib group (46 pairs; TTP, 3.4 mo vs 1.8 mo [P < .001]; OS, 5.9 mo vs 4.4 mo [P = .003]). There was no significant difference in terms of OS with the IPTW approach (P = .108), but there was one in terms of TTP (P < .001). CONCLUSIONS: Within the limitation of a retrospective study, the present data indicate that transarterial chemoembolization combined with RT could be considered as an alternative to the standard sorafenib in the treatment of patients with advanced-stage HCC with PVTT.


Asunto(s)
Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/mortalidad , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compuestos de Fenilurea/administración & dosificación , Trombosis de la Vena/terapia , Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/diagnóstico por imagen , Quimioradioterapia/mortalidad , Comorbilidad , Femenino , Humanos , Incidencia , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Niacinamida/administración & dosificación , Vena Porta/diagnóstico por imagen , Radiografía , República de Corea/epidemiología , Medición de Riesgo/métodos , Índice de Severidad de la Enfermedad , Sorafenib , Tasa de Supervivencia , Resultado del Tratamiento , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/mortalidad
7.
PLoS One ; 8(11): e79854, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24255719

RESUMEN

BACKGROUND: Even with early stage hepatocellular carcinoma (HCC), patients are often ineligible for surgical resection, transplantation, or local ablation due to advanced cirrhosis, donor shortage, or difficult location. Stereotactic body radiation therapy (SBRT) has been established as a standard treatment option for patients with stage I lung cancer, who are not eligible for surgery, and may be a promising alternative treatment for patients with small HCC who are not eligible for curative treatment. MATERIALS AND METHODS: A registry database of 93 patients who were treated with SBRT for HCC between 2007 and 2009 was analyzed. A dose of 10-20 Gy per fraction was given over 3-4 consecutive days, resulting in a total dose of 30-60 Gy. The tumor response was determined using dynamic computed tomography or magnetic resonance imaging, which was performed 3 months after completion of SBRT. RESULTS: The median follow-up period was 25.6 months. Median size of tumors was 2 cm (range: 1-6 cm). Overall patients' survival rates at 1 and 3 years were 86.0% and 53.8%, respectively. Complete and partial tumor response were achieved in 15.5% and 45.7% of patients, respectively. Local recurrence-free survival rate was 92.1% at 3 years. Most local failures were found in patients with HCCs > 3 cm, and local control rate at 3 years was 76.3% in patients with HCC > 3 cm, 93.3% in patients with tumors between 2.1-3 cm, and 100% in patients with tumors ≤ 2 cm, respectively. Out-of-field intrahepatic recurrence-free survival rates at 1 and 3 years were 51.9% and 32.4%, respectively. Grade ≥ 3 hepatic toxicity was observed in 6 (6.5%). CONCLUSIONS: SBRT was effective in local control of small HCC. SBRT may be a promising alternative treatment for patients with small HCC which is unsuitable for other curative therapy.


Asunto(s)
Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Radiocirugia , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/mortalidad , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Dosis de Radiación , Radiocirugia/efectos adversos , Planificación de la Radioterapia Asistida por Computador , Sistema de Registros , Retratamiento , Insuficiencia del Tratamiento , Resultado del Tratamiento , Carga Tumoral
8.
Radiology ; 269(2): 603-11, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23864102

RESUMEN

PURPOSE: To compare the time to progression (TTP) and overall survival (OS) in patients with advanced-stage hepatocellular carcinoma (HCC) who are undergoing sorafenib treatment combined with transarterial chemoembolization (TACE) versus sorafenib monotherapy. MATERIALS AND METHODS: The retrospective analysis of the data was approved by the institutional review board, and the requirement to obtain informed consent was waived. Of 355 patients with advanced-stage HCC (Barcelona Clinic Liver Cancer stage C) who were undergoing sorafenib therapy for at least 5 weeks between April 2007 and July 2011, 164 (46.2%) underwent repeat TACE (or chemolipiodolization if indicated) along with sorafenib therapy (combined group); the remaining 191 patients (53.8%) received sorafenib alone (monotherapy group). The median patient age was 53 years (range, 22-84 years). The median age was 53 years (range, 26-84 years) for men and 56 years (range, 22-75 years) for women. Propensity score-based methods were used to minimize bias when evaluating TTP on the basis of modified Response Evaluation Criteria in Solid Tumors and OS. Statistical analysis was performed with the Kaplan-Meier method by using the log-rank test and Cox regression models. RESULTS: In the combined and monotherapy groups, respectively, 64.6% and 49.2% of patients had vascular invasion, 87.8% and 91.1% had extrahepatic metastasis, and 54.3% and 47.1% had both. During follow-up (median duration, 5.5 months), the median TTP and OS in the combined group were longer than those in the monotherapy group (TTP: 2.5 months vs 2.1 months, respectively, P = .008; OS: 8.9 months vs 5.9 months, P = .009). At univariate and subsequent multivariate analyses, additional TACE was an independent predictor of favorable TTP and OS (adjusted hazard ratio: 0.74 and 0.57, respectively; P < .05 for both), consistent with the outcomes of inverse probability of treatment weighting. In the propensity score-matched cohort (96 pairs), the median TTP in the combined group was significantly longer than that in the monotherapy group (2.7 months vs 2.1 months, respectively; P = .011), but median OS was not (9.1 months vs 6.7 months, P = .21). CONCLUSION: In this retrospective study, TACE plus sorafenib was superior to sorafenib alone with respect to TTP in patients with advanced-stage HCC, although it may or may not improve OS. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13130150/-/DC1.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/patología , Terapia Combinada , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Niacinamida/uso terapéutico , Puntaje de Propensión , Estudios Retrospectivos , Sorafenib , Tasa de Supervivencia , Resultado del Tratamiento
9.
Liver Int ; 33(3): 327-37, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23331661

RESUMEN

Hepatocellular carcinoma (HCC) presents with a high burden of disease in East Asian countries. Intermediate-stage HCC as defined by the Barcelona Clinic Liver Cancer (BCLC) staging system poses a clinical challenge as it includes a heterogeneous population of patients that can vary widely in terms of tumour burden, liver function and disease aetiology. Intermediate HCC patients often have unsatisfactory clinical outcomes with repeated transarterial chemoembolization (TACE, due to non-response of the target tumour or the development of further metastasis indicating progressive disease. In September 2011, an Expert Panel Opinion on Interventions in Hepatocellular Carcinoma (EPOIHCC) was convened in HK in an attempt to provide a consensus on the practice of TACE. To that end, current clinical practice throughout Asia was reviewed in detail including safety and efficacy data on TACE alone as well as in combination with targeted systemic therapies. This review summarises the evidence discussed at the meeting and provides expert recommendation regarding the available therapeutic options for unresectable intermediate stage HCC. A key consensus of the Expert Panel was that in order to improve patient outcomes and long-term survival, the possibility of using TACE in combination with targeted agents given systemically should be explored. While the currently available clinical data is promising, the expected completion of several pivotal phase II and III RCTs will provide further evidence in support of the rationale for combination therapy regimens.


Asunto(s)
Antineoplásicos/uso terapéutico , Pueblo Asiatico , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Quimioembolización Terapéutica/normas , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compuestos de Fenilurea/uso terapéutico , Carcinoma Hepatocelular/etnología , Humanos , Neoplasias Hepáticas/etnología , Niacinamida/uso terapéutico , Sorafenib
10.
Dig Dis Sci ; 58(6): 1758-65, 2013 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-23361574

RESUMEN

BACKGROUND AND AIM: The aim of our study was to determine the predictors of recurrences in hepatocellular carcinoma (HCC) patients who had achieved complete remission (CR) by transarterial chemoembolization (TACE). METHODS: A total of 220 consecutive HCC patients who had achieved CR by TACE were followed for a median 72 months. CR was defined as complete lipiodol uptake based on the results of lipiodol-computed tomography 4 weeks after TACE and no additional tumor staining on the follow-up angiography. Recurrence patterns were classified as local recurrence and secondary tumor, respectively, in relation to the location of recurrence; early and late recurrence were classified in relation to recurrence time. RESULTS: Recurrence of HCC was observed in 169 patients (77 %), of whom 91 (54 %) had local recurrences, 61 (36 %) had secondary tumor, and 17 (10 %) had both. There were 45 (27 %) early and 124 (73 %) late recurrences. Local recurrence developed more frequently in patients with early recurrence than in those with late recurrence (62 vs. 51 %, respectively), while secondary tumor was detected more commonly in patients with late recurrence than in those with early recurrence (39 vs. 29 %, respectively; P < 0.001). In multivariate analyses, multinodularity [hazard ratio (HR) 2.351, P = 0.023] and a persistently high serum alpha-fetoprotein level following CR (HR 3.173, P < 0.001) were significant predictors of early recurrence. Older age (≥ 60 years; HR 1.531, P = 0.043), advanced Child-Pugh class (HR 1.983, P = 0.002), and the association with cirrhosis (HR 1.756, P = 0.028) were predictors of late recurrence following CR. CONCLUSIONS: Early recurrences following CR by TACE may be due mainly to undetectable remaining tumors, whereas late recurrences may be caused by newly appearing tumors in patients with a background of advanced cirrhotic liver.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Recurrencia Local de Neoplasia/etiología , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/métodos , Cisplatino/administración & dosificación , Aceite Etiodizado/administración & dosificación , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia/mortalidad , Inducción de Remisión , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia , Resultado del Tratamiento
11.
J Vasc Interv Radiol ; 24(3): 316-25, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23312990

RESUMEN

PURPOSE: To determine the usefulness of enhancement by iodized oil deposits on computed tomography (CT) following transarterial chemoembolization for hepatocellular carcinoma (HCC), and to compare the reliability of such CT imaging with that of magnetic resonance (MR) imaging. MATERIALS AND METHODS: Fifty-one patients for whom resected or explanted livers containing chemoembolized HCC lesions of at least 1 cm were available. Imaging responses were determined based on modified Response Evaluation Criteria In Solid Tumors (mRECIST) and European Association for the Study of the Liver (EASL) criteria for 59 target tumors on CT and MR scans before surgery. CT-based evaluation was performed per mRECIST and EASL criteria, considering iodized oil retention as indicating necrosis and, alternatively, as enhancing viable tissue ("mRECIST-Lipiodol" and "EASL-Lipiodol"). Pathologic necrosis was graded as 100%, 50%-99%, or less than 50%. RESULTS: Goodman-Kruskal γ-values for radiologic-pathologic correlation were greater than 0.95 for mRECIST and EASL criteria on CT or MR imaging. However, mRECIST-Lipiodol and EASL-Lipiodol measurements showed weaker correlation with pathologic findings, with γ-values of 0.797 and 0.846, respectively. With respect to intermethod agreement, weighted γ-values for mRECIST by CT and MR, and for EASL criteria by CT and MR, both exceeded 0.80, whereas mRECIST-Lipiodol and EASL-Lipiodol showed only moderate levels of agreement with mRECIST/EASL criteria by CT or MR imaging, with γ-values of 0.522-0.631. CONCLUSIONS: Response estimation based on measurement of iodized oil deposits as necrosis on CT when applying enhancement criteria after chemoembolization for HCC correlated well with actual pathologic class, and agreed with MR-based evaluation.


Asunto(s)
Antibióticos Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Doxorrubicina/administración & dosificación , Portadores de Fármacos , Aceite Etiodizado/administración & dosificación , Neoplasias Hepáticas/terapia , Imagen por Resonancia Magnética , Tomografía Computarizada Multidetector , Adulto , Anciano , Antibióticos Antineoplásicos/efectos adversos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/efectos adversos , Doxorrubicina/efectos adversos , Aceite Etiodizado/efectos adversos , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Necrosis , Estadificación de Neoplasias , Tamaño de la Partícula , Valor Predictivo de las Pruebas , Reproducibilidad de los Resultados , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento
12.
Cancer ; 119(1): 136-42, 2013 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-22736425

RESUMEN

BACKGROUND: Sorafenib currently sets the new standard for advanced hepatocellular carcinoma (HCC). It has been suggested that Asian patients with HCC have increased susceptibility to hand-foot skin reaction (HFSR) related to sorafenib therapy. The authors investigated the association between sorafenib-induced HFSR and genetic polymorphisms in Korean patients with HCC. METHODS: For this prospective cohort study, the authors enrolled 59 consecutive patients with intermediate stage HCC from 5 centers in Korea. All patients received sorafenib 400 mg twice daily in combination with transarterial chemoembolization (TACE). Genotyping was performed on a total of 49 single nucleotide polymorphisms (SNPs) in 8 candidate genes (minor allelic frequency ≥5%). Serum levels of vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) were measured using enzyme-linked immunosorbent assays before therapy and 1 month after therapy. RESULTS: During a median treatment period of 18 months, 55 patients (93%) developed sorafenib-induced HFSR, including grade 1 reactions in 15 patients, grade 2 reactions in 27 patients, and grade 3 reaction in 13 patients. The SNPs TNF-α -308GG, VEGF -94GG, VEGF 1991CC, VEGF IVS3-28CC, and uridine diphosphate glucuronosyltransferase 1 family-polypeptide A9 (UGT1A9) IVS1-37431AA were associated significantly with the development of high-grade (grade 2 or 3) HFSR in univariate analysis (P < .05). In multivariate analysis, the SNPs VEGF 1991CC (odds ratio, 45.7), TNF-α -308GG (odds ratio, 44.1), and UGT1A9 IVS1-37431AA (odds ratio, 18.7) were identified as independent risk factors for the development of high-grade HFSR (P = .01, P = .02, and P = .02, respectively). He serum TNF-α level measured 1 month after sorafenib therapy was correlated significantly with the development of high-grade HFSR (odds ratio, 3.56; P = .026). CONCLUSIONS: Differences in the incidence of HFSR may have been caused by ethnic differences in genetic polymorphisms of the TNF-α, VEGF, and UGT1A9 genes, especially in relation to the expression of serum TNF-α after sorafenib therapy.


Asunto(s)
Antineoplásicos/efectos adversos , Bencenosulfonatos/efectos adversos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Predisposición Genética a la Enfermedad , Síndrome Mano-Pie/etiología , Síndrome Mano-Pie/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Polimorfismo de Nucleótido Simple , Piridinas/efectos adversos , Adulto , Anciano , Carcinoma Hepatocelular/etnología , Femenino , Humanos , Corea (Geográfico) , Neoplasias Hepáticas/etnología , Masculino , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Sorafenib , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética , Factor A de Crecimiento Endotelial Vascular/sangre
13.
J Gastroenterol ; 47(10): 1115-24, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22526269

RESUMEN

BACKGROUND: Post-transplant outcomes for acute liver failure (ALF) are unsatisfactory, and there are debates about the most suitable type of graft. Given the critical shortage of donor organs, accurate assessment of post-transplant outcome in ALF patients is crucial to avoid a futile liver transplantation (LT). METHODS: A database of 160 consecutive adult ALF patients who underwent primary LT between 2000 and 2009 in a tertiary LT center was analyzed. RESULTS: The most common causes of ALF were hepatitis B virus infection (30%) and herbal/folk medicine use (30%). Thirty-six (22.5%) and 124 (77.5%) patients underwent deceased-donor LT (DDLT) and adult-to-adult living-donor LT (LDLT), respectively. During a median follow-up period of 38 (range 1-132) months, the DDLT and LDLT groups showed similar patient (P = 0.99) and graft (P = 0.97) survival rates. The overall 1- and 3-year patient survival rates were 78.8 and 74.6%, respectively. Five predictors of patient survival were identified by bootstrapping and multivariate analysis: vasopressor requirement, estimated glomerular filtration rate, serum sodium concentration, recipient age, and donor age, at the time of transplant. By summing scores weighted in each of these predictor categories, we designed a prognostic scoring system (scores from -2 to 20) that estimated 1-year post-transplant mortality from 0 to 100% (c statistic 0.79). CONCLUSIONS: Long-term outcomes after LDLT and DDLT were comparable in adult patients with ALF. A simple prognostic scoring system that includes 5 predictive variables at the time of LT may help estimate post-transplant survival in ALF patients, regardless of the type of transplant.


Asunto(s)
Fallo Hepático Agudo/mortalidad , Fallo Hepático Agudo/cirugía , Trasplante de Hígado , Donadores Vivos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Donantes de Tejidos , Resultado del Tratamiento
14.
Oncology ; 82(2): 119-25, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22354124

RESUMEN

OBJECTIVE: Although sorafenib has shown survival benefits in patients with hepatocellular carcinoma (HCC), many patients require discontinuation or dose reduction due to adverse events (AEs). We applied a dose escalation scheme to increase patient compliance and avoid AEs. METHODS: Of 267 HCC patients treated with first-line sorafenib, 25 at increased risk of AEs, including those with advanced liver cirrhosis, a history of liver transplantation, or cytopenia, received the dose escalation scheme. They started on a reduced dose of sorafenib which increased to the standard dosage according to tolerance in each patient. We analyzed the efficacy and safety of the dose escalation scheme. RESULTS: Patients with risk factors showed a lower disease control rate, shorter survival, and more frequently grade 3/4 AEs. Among patients presenting risk factors, the dose scheme did not affect the efficacy of sorafenib or survival, but reduced the incidence of grade 3/4 AEs. Rates of sorafenib discontinuation and dose reduction related to AEs were also lower in the dose escalation group. Dose escalation to the standard dose of sorafenib was achieved in 16 of the 25 patients in the dose escalation group (64.0%). After 2 weeks, the dose intensity of sorafenib did not differ between the two dose schemes. CONCLUSIONS: The sorafenib dose escalation scheme may increase patient compliance and tolerance to prolonged treatment, thus enhancing the efficacy of sorafenib in patients at high risk of AEs or with poor tolerance. Further prospective analyses are needed to determine the usefulness of the dose escalation scheme.


Asunto(s)
Antineoplásicos/administración & dosificación , Bencenosulfonatos/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Piridinas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Bencenosulfonatos/efectos adversos , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Piridinas/efectos adversos , Sorafenib
15.
Int J Radiat Oncol Biol Phys ; 82(5): 2004-11, 2012 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-21621346

RESUMEN

PURPOSE: We have evaluated the clinical outcomes of patients after transarterial chemoembolization (TACE) and 3-dimensional conformal radiotherapy for hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT). METHODS AND MATERIALS: A registry database of 412 patients treated with TACE and three-dimensional conformal radiotherapy for HCC with PVTT between August 2002 and August 2008 were analyzed retrospectively. The radiotherapy volume included the PVTT, with a 2- to 3-cm margin to cover adjacent HCC. Intrahepatic primary HCC was managed by TACE before or after radiotherapy. RESULTS: Median patient age was 52 years old, and 88.1% of patients were male. Main or bilateral PVTT was observed in 200 (48.5%) patients. Median radiation dose was 40 Gy (range, 21-60 Gy) delivered in 2- to 5-Gy fractions. We found that 3.6% of patients achieved a complete response and that 24.3% of patients achieved a partial response. The response and progression-free rates of PVTT were 39.6% and 85.6%, respectively. Median patient survival was 10.6 months, and the 1- and 2-year survival rates were 42.5% and 22.8%, respectively. Significant independent variables associated with overall survival included advanced tumor stage, alpha-fetoprotein level, degree of PVTT, and response to radiotherapy. Forty-one patients (10.0%) showed grade 3-4 hepatic toxicity during or 3 months after completion of radiotherapy. Grades 2-3 gastroduodenal complications were observed in 15 patients (3.6%). CONCLUSIONS: Radiotherapy is a safe and effective treatment for PVTT in patients with HCC. These results suggested that the combination of TACE and radiotherapy is a treatment option for relieving and/or stabilizing PVTT in patients with advanced HCC.


Asunto(s)
Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica/métodos , Neoplasias Hepáticas/terapia , Vena Porta , Radioterapia Conformacional/métodos , Trombosis de la Vena/terapia , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Carcinoma Hepatocelular/sangre , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Quimioembolización Terapéutica/efectos adversos , Cisplatino/administración & dosificación , Terapia Combinada/métodos , Supervivencia sin Enfermedad , Aceite Etiodizado/administración & dosificación , Femenino , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Vena Porta/patología , Dosificación Radioterapéutica , Radioterapia Conformacional/efectos adversos , Inducción de Remisión/métodos , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento , Trombosis de la Vena/etiología , Adulto Joven , alfa-Fetoproteínas/metabolismo
16.
J Med Virol ; 83(7): 1195-202, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21567423

RESUMEN

The epidemiology and clinical outcomes of acute hepatitis C are different geographically. This study aimed to investigate the mode of infection, clinical characteristics, and outcomes of acute hepatitis C in Korea. Forty-seven patients with acute hepatitis C were enrolled consecutively in a study conducted in seven medical centers. The patients with the mean age of 45.8 years had mostly mild symptoms. A healthcare-related procedure was the most common exposure history (42.5%): acupuncture (17%), surgery (10.6%), needle-stick injury (8.5%), and other medical procedures (6.4%). There was no case of intravenous drug use. Twenty-one patients (44.7%) recovered spontaneously. Among the 16 patients who received antiviral therapy (34%), all of the 12 evaluable patients had a sustained virologic response, while 10 patients (21.3%) who did not receive antiviral therapy progressed to chronic infection. The overall seroconversion rate of anti-HCV antibody was 61.7%. The patients who recovered spontaneously had significantly lower rate of seroconversion compared with the patients who did not clear spontaneously the infection. In conclusion, acute hepatitis C in Korea was related to various healthcare procedures, including acupuncture, characterized by high rates of spontaneous recovery and low rates of seroconversion, which may be associated with different modes of infection and ethnic differences. The characteristics of acute hepatitis C in Asian countries warrants further study.


Asunto(s)
Hepatitis C/transmisión , Acupuntura , Enfermedad Aguda , Adulto , Anciano , Alanina Transaminasa/análisis , Antivirales/uso terapéutico , Femenino , Hepacivirus/fisiología , Hepatitis C/diagnóstico , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Anticuerpos contra la Hepatitis C/análisis , Anticuerpos contra la Hepatitis C/biosíntesis , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Lesiones por Pinchazo de Aguja/sangre , ARN Viral/análisis , Remisión Espontánea , República de Corea , Factores de Riesgo , Procedimientos Quirúrgicos Operativos/efectos adversos , Resultado del Tratamiento , Adulto Joven
17.
Cancer Chemother Pharmacol ; 68(5): 1285-90, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21445543

RESUMEN

PURPOSE: We compared the efficacy and safety of sorafenib in patients with Child-Pugh (CP) class B and CP class A. METHODS: Clinical data from 267 patients with HCC who had been treated with sorafenib were reviewed. Patients were grouped according to CP score (5-6, 7, and 8-9), and their tumor response, tolerance, and survival were assessed. RESULTS: Median patient age was 55 years, and 87.6% were men. Gender, HCC etiology, and extrahepatic metastasis did not differ according to CP score. Of the 225 evaluable patients, 4 achieved partial response and 121 achieved stable disease, making the disease control rate 46.8%. DCR was higher in patients with CP A than CP B score, but did not differ between those with CP scores of 7 and 8-9. The incidence rates of grade 3/4 toxicities did not differ according to CP score. Many patients with CP score 8-9 (26.3%) had to stop sorafenib due to cirrhosis-related complications. At a median follow-up of 15.6 months, the median time to progression and overall survival of all patients were 2.6 and 7.9 months, respectively. OS was greater in patients with CP score 5-6 than in patients with CP scores of 7 or 8-9. CONCLUSIONS: Sorafenib efficacy and survival outcomes were worse in patients with CP B function. Patients with a CP score of 7 had the same incidence of adverse events and cirrhosis-related complications as those with CP A liver function, suggesting that the former can be included in clinical trials of new agents.


Asunto(s)
Antineoplásicos/uso terapéutico , Bencenosulfonatos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Piridinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Bencenosulfonatos/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Piridinas/efectos adversos , Sorafenib , Resultado del Tratamiento
18.
J Gastroenterol Hepatol ; 26(1): 145-54, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-21175808

RESUMEN

BACKGROUND AND AIMS: The therapeutic efficacy of transarterial chemoembolization (TACE) has not been evaluated in hepatocellular carcinoma (HCC) patients with extrahepatic metastasis. We investigated the efficacy of TACE with/without systemic chemotherapy (s-chemo) in these patients. METHODS: We performed a survival analysis of consecutive HCC patients with extrahepatic metastasis, diagnosed at initial presentation according to treatment modality after stratification, using the Child-Pugh classification and intrahepatic HCC T stage, retrospectively. RESULTS: Between 2005 and 2007, 251 patients were newly diagnosed with HCC involving extrahepatic metastasis at our institution. Among those, 226 were classified as Child-Pugh A-B and the other 25, Child-Pugh C. Within the Child-Pugh A-B group, repeated TACE or transarterial chemoinfusion (TACI) was performed with/without s-chemo in 171 patients. Eight of 226 received s-chemo alone, and 47, conservative management (CM) alone. The median survival time of patients treated with TACE/TACI with s-chemo, TACE/TACI alone, and CM was 10, 5, and 2.9 months in patients classified as Child-Pugh A and T3-stage HCC (TACE/TACI with s-chemo vs CM, P=0.0354; TACE/TACI alone vs CM, P=0.0553) and 7.1, 2.6, and 1.6 months in Child-Pugh B and T3-stage patients, respectively (TACE/TACI with s-chemo vs CM, P=0.0097; TACE/TACI alone vs CM, P<0.0001). Individual treatment with TACE/TACI or sorafenib showed independent prognostic significance in the multivariate analysis. CONCLUSION: Repeated TACE could show significant survival benefits in metastatic HCC patients with conserved liver function and intrahepatic HCC T3 stage. The survival data of our study could be used as a historical control for TACE monotherapy in future clinical trials evaluating combination treatments containing TACE in these patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/terapia , Quimioembolización Terapéutica , Neoplasias Hepáticas/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bencenosulfonatos/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/secundario , Causas de Muerte , Distribución de Chi-Cuadrado , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Modelos de Riesgos Proporcionales , Inhibidores de Proteínas Quinasas/administración & dosificación , Piridinas/administración & dosificación , República de Corea , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Sorafenib , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
19.
Jpn J Clin Oncol ; 40(8): 768-73, 2010 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-20494947

RESUMEN

OBJECTIVE: Sorafenib is the only drug that has shown a survival benefit in patients with hepatocellular carcinoma in randomized Phase 3 trials. The efficacy and safety of sorafenib in the treatment of recurrent hepatocellular carcinoma after liver transplantation, however, has not been determined. METHODS: We retrospectively analyzed 13 patients who were treated with sorafenib for recurrent hepatocellular carcinoma after liver transplantation. RESULTS: The median time to recurrence from liver transplantation was 12.3 months (95% confidence interval: 8.5-16.1 months). Six of 10 evaluable patients showed stable disease, which was the best response and the median duration of stabilization was 3.9 months (95% confidence interval: 1.6-6.2 months). At a median follow-up duration of 3.7 months (range: 0.3-10.9 months) in surviving patients, the median time to progression and the median overall survival from commencement of sorafenib were 2.9 months (95% confidence interval: 0.0-6.8 months) and 5.4 months (95% confidence interval: 3.7-7.0 months), respectively. Grade 3 neutropenia was observed in one patient, which was the only high-grade hematologic toxicity observed. Grade 3 hand-foot skin reactions were observed in three patients. Adverse events could be managed with dose adjustment. CONCLUSIONS: These findings suggest that sorafenib may be a feasible treatment option regarding its efficacy and safety for recurrent hepatocellular carcinoma after liver transplantation.


Asunto(s)
Antineoplásicos/uso terapéutico , Bencenosulfonatos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Recurrencia Local de Neoplasia/tratamiento farmacológico , Piridinas/uso terapéutico , Adulto , Antineoplásicos/efectos adversos , Bencenosulfonatos/efectos adversos , Carcinoma Hepatocelular/mortalidad , Progresión de la Enfermedad , Erupciones por Medicamentos/etiología , Femenino , Enfermedades Hematológicas/inducido químicamente , Humanos , Neoplasias Hepáticas/mortalidad , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Inhibidores de Proteínas Quinasas/efectos adversos , Inhibidores de Proteínas Quinasas/uso terapéutico , Piridinas/efectos adversos , Estudios Retrospectivos , Sorafenib , Tasa de Supervivencia
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