RESUMO
BACKGROUND: In patients with advanced hepatocellular carcinoma (HCC), evidence is unclear as to whether hepatic arterial infusion chemotherapy (HAIC) or sorafenib is superior. We performed a prospective, open-label, non-comparative phase II study to assess survival with HAIC or HAIC converted to sorafenib. METHODS: Fifty-five patients were prospectively enrolled. Patients received HAIC as a second course if they had complete response, partial response, or stable disease (SD) with an alpha fetoprotein (AFP) ratio < 1 or a des-γ-carboxy prothrombin (DCP) ratio < 1. Patients were switched to sorafenib if they had SD with an AFP ratio > 1 and a DCP ratio > 1 or disease progression. The primary endpoint was the 1-year survival rate. Secondary endpoints were the 2-year survival rate, HAIC response, survival rate among HAIC responders, progression-free survival, and adverse events. RESULTS: Of the 55 patients in the intent-to-treat population, the 1-year and 2-year survival rates were 64.0 and 48.3%, respectively. After the first course of HAIC, one (1.8%) patient showed complete response, 13 (23.6%) showed partial response, 30 (54.5%) had SD, and 10 (18.1%) patients had progressive disease. Twenty-three patients (41.8%) had SD with AFP ratios < 1 or DCP ratios < 1, and 7 (12.7%) had SD with AFP ratios > 1 and DCP ratios > 1. Thirty-seven patients (68.5%) were responders and 17 (30.9%) were non-responders to HAIC. In responders, the 1-year and 2-year survival rates were 78 and 62%, respectively. CONCLUSION: Given the results of this study, this protocol deserves consideration for patients with advanced HCC. This trial was registered prospectively from December 12. 2012 to September 1. 2016.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Infusões Intra-Arteriais/métodos , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Cisplatino/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Resultado do TratamentoRESUMO
OBJECTIVE: To compare the outcome of hepatic arterial infusion chemotherapy combined with radiotherapy (HAIC + RT) versus sorafenib monotherapy in patients with advanced hepatocellular carcinoma (HCC) and major portal vein tumor thrombosis (PVTT). METHODS: This retrospective study included 108 HCC patients with PVTT of the main trunk or first branch and Child-Pugh ≤7. Sixty-eight received HAIC + RT and 40 received sorafenib. Patients were then assigned to the HAIC + RT group (n = 36) and the sorafenib group (n = 36) through case-control matching. The decision to treat with HAIC + RT or sorafenib was left to the attending physician. RESULTS: The median overall, progression-free, and postprogression survival were significantly longer in the HAIC + RT group than in the sorafenib group (9.9 vs. 5.3, p = 0.002; 3.9 vs. 2.1, p = 0.048; and 3.7 vs. 1.9 months, p = 0.02, respectively). Multivariate analysis identified HAIC + RT (hazard ratio = 2.02; 95% confidence interval, 1.14-3.57; p = 0.01) as a significant and independent determinant of overall survival. CONCLUSIONS: In patients with advanced HCC and major PVTT, survival was significantly longer in those treated with HAIC + RT than with sorafenib.
Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Veia Porta/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Hepatocelular/mortalidade , Quimiorradioterapia/efeitos adversos , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Interferons/administração & dosagem , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Células Neoplásicas Circulantes , Niacinamida/efeitos adversos , Niacinamida/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Radioterapia Conformacional/efeitos adversos , Estudos Retrospectivos , Sorafenibe , Taxa de SobrevidaRESUMO
OBJECTIVE: To evaluate the impact of hepatitis C virus (HCV) eradication on the clinical outcome of patients with HCV-related advanced hepatocellular carcinoma (HCC) treated with sorafenib. METHODS: A total of 58 HCV-related advanced HCC patients with Child-Pugh grade A disease who were treated with sorafenib were enrolled in this retrospective cohort study. Of these, 27 patients were HCV RNA negative as a result of previous antiviral therapy (sustained viral response [SVR] group), while the remaining 31 were HCV RNA positive (non-SVR group). RESULTS: The response rate, disease control rate and median time to progression in the SVR group (6, 46.0%, and 3.8 months, respectively) were similar to those in the non-SVR group (3, 51.5%, and 2.7 months, respectively). On the other hand, the median time to treatment failure (TTTF), post-progression survival (PPS), and overall survival (OS) were significantly longer in the SVR group than in the non-SVR group (9.7, 8.5, and 15 months vs. 5.9, 5.2, and 9.3 months; p = 0.023, 0.02, and 0.014, respectively). On multivariate analysis, SVR was identified as a significant and independent determinant of PPS (p = 0.009), TTTF (p = 0.028), and OS (p = 0.01). CONCLUSION: HCV eradication before sorafenib treatment for HCV-related advanced HCC could prolong PPS and TTTF and improve OS.
Assuntos
Antineoplásicos/uso terapêutico , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/virologia , Progressão da Doença , Intervalo Livre de Doença , Feminino , Hepacivirus/efeitos dos fármacos , Humanos , Japão , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Niacinamida/uso terapêutico , Estudos Retrospectivos , Sorafenibe , Tempo para o Tratamento , Resultado do TratamentoRESUMO
Even with current promising antitumor antibodies, their antitumor effects on stroma-rich solid cancers have been insufficient. We used mild hyperthermia with the intent of improving drug delivery by breaking the stromal barrier. Here, we provide preclinical evidence of cetuximab + mild hyperthermia therapy. We used four in vivo pancreatic cancer xenograft mouse models with different stroma amounts (scarce, MIAPaCa-2; moderate, BxPC-3; and abundant, Capan-1 and Ope-xeno). Cetuximab (1 mg/kg) was given systemically, and the mouse leg tumors were concurrently heated using a water bath method for 30 min at three different temperatures, 25°C (control), 37°C (intra-abdominal organ level), or 41°C (mild hyperthermia) (n = 4, each group). The evaluated variables were the antitumor effects, represented by tumor volume, and in vivo cetuximab accumulation, indirectly quantified by the immunohistochemical fluorescence intensity value/cell using antibodies against human IgG Fc. At 25°C, the antitumor effects were sufficient, with a cetuximab accumulation value (florescence intensity/cell) of 1632, in the MIAPaCa-2 model, moderate (1063) in the BxPC-3 model, and negative in the Capan-1 and Ope-xeno models (760, 461). By applying 37°C or 41°C heat, antitumor effects were enhanced shown in decreased tumor volumes. These enhanced effects were accompanied by boosted cetuximab accumulation, which increased by 2.8-fold (2980, 3015) in the BxPC-3 model, 2.5- or 4.8-fold (1881, 3615) in the Capan-1 model, and 3.2- or 4.2-fold (1469, 1922) in the Ope-xeno model, respectively. Cetuximab was effective in treating even stroma-rich and k-ras mutant pancreatic cancer mouse models when the drug delivery was improved by combination with mild hyperthermia.