RESUMO
INTRODUCTION: Local therapies for high risk non-muscle-invasive bladder cancer (NMIBC) such as intravesical chemotherapy (IVC) have shown a high rate of progression and recurrence. Intravesical Bacillus Calmette-Guérin (BCG) for local therapies has been shown to reduce progression and recurrence in patient with NMIBC. However, its potential role is limited in high burden countries for tuberculosis (TB) due to its low specificity that can cause wrong diagnosis or false positive in patients with clinically diagnosed tuberculosis. BCG vaccine that has to be given for most people in tuberculosis endemic countries will induce trained immunity that could reduce the effectivity of intravesical BCG for NMIBC. Moreover, intravesical BCG is contraindicated in patient with or previous tuberculosis. The potential clinical benefit of intraarterial chemotherapy (IAC) in delaying the recurrence and progression of high-risk NMIBC have been investigated with promising results. We aimed to conduct a meta-analysis to evaluate the potential anti-tumor effect of IAC in NMIBC. METHODS: We conducted a comprehensive search of published articles in Cochrane Library, Pubmed, and Science-Direct to identify relevant randomized controlled trials (RCTs) and observational studies comparing IAC alone or combined with IVC versus IVC/BCG alone in NMIBC. The protocol of preferred reporting items for systematic review and meta-analysis (PRISMA) was applied to this study. RESULTS: Four RCTs and 4 cohort observational studies were eligible in this study and 5 studies were included in meta-analysis. The risk ratio of tumor recurrence was reduced by 35% (RR = 0.65; 95% CI 0.49-0.87; p = 0.004) in IAC plus IVC, while recurrence-free survival (RFS) was prolonged by 45% (HR: 0.55; 95% CI, 0.44-0.69; p < 0.001). The risk of tumor progression was reduced by 45% (RR = 0.55; 95% CI 0.41-0.75; p = 0.002) and tumor progression-free survival (PFS) was also prolonged by 53% (HR: 0.47; 95% CI, 0.34-0.65; p<0.001). Some RCT's had high or unclear risk of bias, meanwhile 4 included cohort studies had overall low risk of bias, therefore the pooled results need to be interpreted cautiously. Subgroup analysis revealed that the heterogeneity outcome of tumour recurrence might be attributed to the difference in NMIBC stages and grades. CONCLUSIONS: The IAC alone or combined with IVC following bladder tumor resection may lower the risk of tumor recurrence and progression. These findings highlight the importance of further multi institutional randomized controlled trials with bigger sample size using a standardized IAC protocol to validate the current results.
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Invasividade Neoplásica , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Humanos , Vacina BCG/administração & dosagem , Vacina BCG/uso terapêutico , Tuberculose/tratamento farmacológico , Administração Intravesical , Infusões Intra-Arteriais , Antineoplásicos/administração & dosagem , Recidiva Local de Neoplasia , Progressão da DoençaAssuntos
Carcinoma Hepatocelular , Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Artéria Hepática , Natação , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Infusões Intra-Arteriais , Quimioterapia Adjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêuticoRESUMO
PURPOSE: This study compares the efficacy and safety of lenvatinib and programmed cell death protein (PD)-1 versus lenvatinib alone for advanced hepatocellular carcinoma (Ad-HCC) refractory to hepatic arterial infusion chemotherapy (HAIC). METHODS: From April 2016 to September 2021, 145 patients with Ad-HCC refractory to HAIC based on modified Response Evaluation Criteria in Solid Tumors criteria were enrolled by two radiologists and classified into the HAIC-lenvatinib group (H-L, n = 87) and HAIC-lenvatinib-PD-1 group (H-L-P, n = 58). A propensity score-matching method was used to reduce selective bias. The overall survival (OS) and postprogression-free survival (PPS) rates were compared using the Kaplan-Meier method with log-rank test. Multivariable analyses of independent prognostic factors were evaluated by means of the forward stepwise Cox regression model. RESULTS: After propensity score matching 1:1, the median OS was 43.6 months in the H-L-P group and was significantly longer than that (18.9 months) of the H-L group (p = .009). The median PPS was 35.6 months in the H-L-P group and was significantly longer than that (9.4 months) of the H-L group (p = .009). Multivariate analyses showed that the factors that significantly affected the OS were α-fetoprotein (hazard ratio [HR], 2.14; 95% CI, 1.26-3.98; p = .006), early response to HAIC (HR, 0.44; 95% CI, 1.20-3.85; p = .009), and H-L treatment (HR, 0.52; 95% CI, 0.30-0.86; p = .012). Modified albumin-bilirubin grade (HR, 1.32; 95% CI, 1.03-1.70; p = .026), early response to HAIC (HR, 0.44; 95% CI, 0.25-0.77; p = .004), and H-L (HR, 0.47 ; 95% CI, 0.28-0.78; p = .003) significantly affected the PPS. CONCLUSIONS: This combination therapy of PD-1 inhibitors plus lenvatinib has promising survival benefits in the management of patients with Ad-HCC refractory to HAIC. PLAIN LANGUAGE SUMMARY: Lenvatinib plus programmed death 1 inhibitor is an effective and safe postprogression treatment and improved significantly overall survival and postprogression-free survival compared with lenvatinib alone in patients with advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy.
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Antineoplásicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Antineoplásicos/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Sorafenibe , Neoplasias Hepáticas/patologia , Resultado do Tratamento , Infusões Intra-Arteriais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosAssuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Artéria Hepática/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , FluoruracilaRESUMO
PURPOSE: Various chemotherapy administration methods have been used to prevent liver metastasis (LM) in patients with colorectal cancer (CRC). This network meta-analysis evaluated the efficacy of these different methods in preventing LM in CRC patients who underwent curative surgery. METHOD: A systematic search of randomized controlled trials reporting the efficacy of various adjuvant chemotherapy methods in patients with colorectal cancer who underwent curative surgery was conducted. The primary outcome was the LM rate. RESULTS: This network meta-analysis included 19 studies reporting on 12,588 participants, comparing portal vein infusion chemotherapy (PVIC) versus hepatic arterial infusion chemotherapy (HAIC) versus systematic chemotherapy (SC) versus surgery alone. The HAIC group had the lowest LM rate when compared to the other three groups (odds ratio [OR] of PVIC vs. HAIC: 1.86; OR of SC vs. HAIC: 1.98; and HAIC vs. surgery alone: 0.43). The LM rate did not differ significantly between PVIC, SC, and surgery alone. The recurrence rates were lower for PVIC and HAIC than for surgery alone (the ORs for PVIC and HAIC were 0.73 [95% CI: 0.58-0.92] and 0.45 [95% CI: 0.26-0.77]). The mortality rates of patients undergoing PVIC and HAIC were lower than that of patients undergoing surgery alone (the ORs for PVIC and HAIC were 0.77 [95% CI: 0.64-0.93] and 0.49 [95% CI: 0.24-0.98]). Anastomotic leakage, cardiopulmonary leakage, diarrhea, nausea and vomiting, oral ulceration, wound infection, or ileus did not differ significantly between the four groups. PVIC showed the highest hepatic toxicity rate compared to those for SC, HAIC, and surgery alone. CONCLUSION: HAIC might be a satisfactory method for preventing LM in patients with CRC undergoing curative surgery.
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Carcinoma Hepatocelular , Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como Assunto , Neoplasias Hepáticas/patologia , Infusões Intra-Arteriais , Quimioterapia Adjuvante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/patologia , Fluoruracila , Carcinoma Hepatocelular/patologia , Resultado do Tratamento , Artéria Hepática/patologiaRESUMO
PURPOSE: To report the efficacy and safety of postoperative adjuvant hepatic arterial infusion chemotherapy (HAIC) with 5-fluorouracil and oxaliplatin (FOLFOX) in hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI). PATIENTS AND METHODS: In this randomized, open-label, multicenter trial, histologically confirmed HCC patients with MVI were randomly assigned (1:1) to receive adjuvant FOLFOX-HAIC (treatment group) or routine follow-up (control group). The primary end point was disease-free survival (DFS) by intention-to-treat (ITT) analysis while secondary end points were overall survival, recurrence rate, and safety. RESULTS: Between June 2016 and August 2021, a total of 315 patients (ITT population) at five centers were randomly assigned to the treatment group (n = 157) or the control group (n = 158). In the ITT population, the median DFS was 20.3 months (95% CI, 10.4 to 30.3) in the treatment group versus 10.0 months (95% CI, 6.8 to 13.2) in the control group (hazard ratio, 0.59; 95% CI, 0.43 to 0.81; P = .001). The overall survival rates at 1 year, 2 years, and 3 years were 93.8% (95% CI, 89.8 to 98.1), 86.4% (95% CI, 80.0 to 93.2), and 80.4% (95% CI, 71.9 to 89.9) for the treatment group and 92.0% (95% CI, 87.6 to 96.7), 86.0% (95% CI, 79.9 to 92.6), and 74.9% (95% CI, 65.5 to 85.7) for the control group (hazard ratio, 0.64; 95% CI, 0.36 to 1.14; P = .130), respectively. The recurrence rates were 40.1% (63/157) in the treatment group and 55.7% (88/158) in the control group. Majority of the adverse events were grade 0-1 (83.8%), with no treatment-related death in both groups. CONCLUSION: Postoperative adjuvant HAIC with FOLFOX significantly improved the DFS benefits with acceptable toxicities in HCC patients with MVI.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Resultado do Tratamento , Fluoruracila/efeitos adversos , Infusões Intra-Arteriais , Adjuvantes Imunológicos/uso terapêuticoRESUMO
AIM: To investigate the individualized survival benefit of hepatic arterial infusion chemotherapy (HAIC) and sequential ablation treatment in large hepatocellular carcinoma (HCC) patients. METHODS: Between February 2016 and December 2020, a total of 228 HCC patients (diameter > 5 cm) who underwent HAIC alone (HAIC group, n = 135) or HAIC and sequential ablation (HAIC-ablation group, n = 93) treatment were reviewed. We applied the inverse probability of treatment weighting (IPTW) to adjust for potential bias of two treatment groups. The overall survival (OS) and progression-free survival (PFS) were compared with Kaplan-Meier curves. The Cox regression model was used to identify independent prognostic factors. And a prediction nomogram based on these independent prognostic factors was built, aiming to make probabilistic survival predictions and estimate personalized ablation benefits. RESULTS: After a median follow-up of 17.9 months, HCC patients in the HAIC-ablation group have longer significantly OS and PFS than those in the HAIC alone group (median OS: 22.2 months vs. 14.5 months; median PFS: 8.5 months vs. 4.6 months; both, p < 0.001). The IPTW-adjusted analysis revealed similar findings (both, p < 0.001). Tumor size, tumor number, and treatment modality were identified as independent prognostic factors for OS. The nomogram based on these factors showed favorable discrimination and well calibration. CONCLUSIONS: HAIC and sequential ablation provided significant survival benefits in patients with large HCC. The nomogram could help predict individual survival probabilities and estimate personalized sequential ablation benefits.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Sorafenibe/uso terapêutico , Resultado do TratamentoAssuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Fluoruracila/uso terapêutico , Genômica , Hepatectomia , Artéria Hepática/patologia , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirurgiaRESUMO
BACKGROUND AND OBJECTIVES: Colorectal liver metastasis (CRLM) is a leading cause of morbidity and mortality in patients with colorectal cancer. Hepatic arterial infusion (HAI) chemotherapy has been demonstrated to improve survival in patients with resected CRLM and to facilitate conversion of technically unresectable disease. METHODS: Between 2016 and 2018, n = 22 HAI pumps were placed for CRLM. All patients received systemic chemotherapy concurrently with HAI floxuridine/dexamethasone. Overall survival (OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. RESULTS: HAI pumps were placed in seven patients with completely resected CRLM and 15 patients with unresectable disease. Twenty-one patients received HAI floxuridine with a median of 5 total HAI cycles (interquartile range: 4-7). Biliary sclerosis was the most common HAI-related complication (n = 5, 24%). Of the 13 patients treated to convert unresectable CRLM, 3 (23%) underwent hepatic resection with curative intent after a median of 7 HAI cycles (range: 4-10). For all HAI patients, the mean OS was 26.7 months from CRLM diagnosis, while the median PFS and hepatic PFS from pump placement were 9 and 13 months, respectively. CONCLUSION: Concomitant HAI and systemic therapy can be utilized at multidisciplinary programs for patients with advanced CRLM, both in the adjuvant setting and to facilitate conversion of unresectable disease.
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Neoplasias Colorretais , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais/patologia , Floxuridina , Fluoruracila , Artéria Hepática/patologia , Humanos , Bombas de Infusão , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgiaRESUMO
We investigated the safety and efficacy of circadian chronotherapy via the hepatic artery(chrono-HAI)as a prehepatectomy chemotherapy for initially unresectable colorectal liver metastases. Five-day course of chrono-HAI using 5-FU, l-LV, and L-OHP plus systemic panitumumab with 9-day interval were administered to 24 patients with failure for previous chemotherapy. Response rate and Grade 3 adverse effect(AE) were 63% and 54%, respectively. Among 22 patients( excluding 2 CR patients), conversion surgery could be performed in 10(45%). Two-year overall survival of patients with surgery (58%)was longer in those without(20%, p=0.057). Although incidence of AE was a bit high, chrono-HAI plus systemic panitumumab is an effective prehepatectomy chemotherapy for patients with aggressive colorectal liver metastases.
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Neoplasias Colorretais , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Fluoruracila , Artéria Hepática/patologia , Artéria Hepática/cirurgia , Humanos , Infusões Intra-Arteriais , Leucovorina , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgiaRESUMO
The aim of the current study was to investigate the efficacy and safety of sorafenib and intermittent hepatic arterial infusion chemotherapy with cisplatin for unresectable hepatocellular carcinoma (HCC) with severe portal vein invasion. The antitumor effect was a complete response in 1 of 38 patients, a partial response in 12 patients, stable disease in 16 patients, and progressive disease in 9 patients, for a 34.2% response rate and a 76.3% disease control rate. This regimen had favorable efficacy and acceptable safety and may be feasible for unresectable HCC with severe portal vein invasion.
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Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Infusões Intra-Arteriais/métodos , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/uso terapêutico , Idoso , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Estudos Prospectivos , Sorafenibe/farmacologiaRESUMO
BACKGROUND: The practice of adjuvant hepatic arterial infusion chemotherapy (HAIC) for colorectal liver metastasis (CRLM) varies widely. This meta-analysis investigates the effectiveness of adjuvant HAIC and the influence of variations in HAIC treatment in patients with resected CRLM. METHODS: PRISMA guidelines were followed for this study. The search was limited to comparative studies (HAIC vs non-HAIC) for overall survival. Subgroup meta-analyses using random-effects were performed for type of intra-arterial drug, method of catheter insertion, use of concomitant adjuvant systemic chemotherapy, and study design. RESULTS: Eighteen eligible studies were identified. After excluding overlapping cohorts, fifteen studies were included in the quantitative analysis, corresponding to 3584 patients. HAIC was associated with an improved overall survival (pooled hazard ratio (HR) 0.77; 95%CI 0.64-0.93). Survival benefit of HAIC was most pronounced in studies using floxuridine (HR 0.76; 95%CI: 0.62-0.94), surgical catheter insertion with subcutaneous pump (HR 0.71; 95%CI: 0.61-0.84), and concomitant adjuvant systemic chemotherapy (HR 0.75; 95%CI: 0.59-0.96). The pooled HR of RCTs was 0.91 (95%CI 0.72-1.14), of which only 3 used floxuridine. CONCLUSION: Adjuvant HAIC is a promising treatment for patients with resectable CRLM, in particular HAIC with floxuridine using a surgically placed catheter and a subcutaneous pump, and concomitant systemic chemotherapy.
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Neoplasias Colorretais , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Neoplasias Colorretais/patologia , Fluoruracila/uso terapêutico , Artéria Hepática/patologia , Humanos , Infusões Intra-Arteriais/métodos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Resultado do TratamentoRESUMO
Severe refractory cerebral vasospasm (CV) is a major cause of disability and death in patients with aneurysmal subarachnoid hemorrhage (SAH). One rescue therapy in selected patients is intra-arterial nimodipine, either given as a single shot or as continuous infusion. To evaluate treatment efficacy, we analyzed outcome factors such as the incidence of craniectomy, ventriculo-peritonial (VP) shunting, and tracheotomy after intra-arterial nimodipine infusion. We retrospectively analyzed the rates of cerebral infarction, decompressive craniectomy, VP shunting, and tracheotomy in patients with severe CV after SAH. Three different patient groups were compared: group 1 had only been treated with oral nimodipine and hypervolemic hypertensive therapy (HHT) (2006-2010), group 2 with a single shot of intra-arterial nimodipine (SSN) in addition to oral conservative treatment (2006-2010), and group 3 with continuous intra-arterial nimodipine (CIAN) (2011-2017). The incidence of cerebral infarction was significantly lower in CIAN group (p = 0.005) than in conservative and SSN group. The indication for consecutive decompressive craniectomy was significantly lower in CIAN group in comparison with the conservative group (p = 0.018). The rates of VP shunting and tracheotomy were significantly higher in the CIAN group than in the conservative group (p = 0.028 for VP, and p = 0.003 for tracheotomy). The significantly lower rate of craniectomy in the CIAN group was most probably attributable to the significantly lower rate of CV-induced infarction. The higher rate of tracheotomy reflects more extensive sedation and the need of longer stays on the intensive care unit. Thus, the effect on long-term neurological outcome and quality of life has to be evaluated separately.
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Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Humanos , Infusões Intra-Arteriais , Nimodipina , Qualidade de Vida , Estudos Retrospectivos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/cirurgia , Resultado do Tratamento , Vasodilatadores/uso terapêutico , Vasoespasmo Intracraniano/tratamento farmacológico , Vasoespasmo Intracraniano/etiologiaRESUMO
BACKGROUND: Patients with intermediate to advanced stage hepatocellular carcinoma (HCC; Barcelona Clinic Liver Cancer [BCLC] stage B/C) have few choices of curable treatments and thus suffer from dismal outcomes. Although surgical resection could prolong survival in certain selected patients with BCLC stage B/C HCC, the frequent postoperative recurrence and poor survival of these patients need to be improved by combining other therapies perioperatively. OBJECTIVE: This study was conducted to investigate the survival associations of adjuvant portal vein perfusion chemotherapy (PVC) and neoadjuvant hepatic arterial infusion chemotherapy (HAIC) in patients with resectable BCLC stage B/C HCC. METHODS: A retrospective study was conducted in consecutive patients who underwent R0 resection for intermediate to advanced stage HCC, combined with either PVC or HAIC perioperatively between January 2017 and December 2018. Patients treated with PVC or HAIC were analyzed according to intention-to-treat (ITT) and per protocol (PP) principles, respectively. The chemotherapy regimen of adjuvant PVC and neoadjuvant HAIC included 5-fluorouracil/leucovorin/oxaliplatin. Survival analysis and Cox regression for overall survival (OS) and event-free survival (EFS) were used to compare the outcomes. RESULTS: Among all 64 patients enrolled in this study, 28 received perioperative PVC and 36 received HAIC for ITT analysis. Age (median 44.00 vs. 46.50 years; p = 0.364), sex (male: 25/28 vs. 35/36; p = 0.435), and tumor size (median 9.55 vs. 8.10 cm; p = 0.178) were comparable between the two groups. In the ITT analysis, the median OS was significantly longer in patients in the HAIC group compared with the PVC group (median OS not reached vs. 19.47 months; p = 0.004); in the PP analysis, patients who received neoadjuvant HAIC followed by hepatectomy presented with much better EFS than patients in the PVC group (modified EFS 16.90 vs. 3.17 months; p = 0.022); and in the multivariate analysis, neoadjuvant HAIC presented as a significant predictor for enhanced EFS (hazard ratio [HR] 0.296; p = 0.007) and OS (HR 0.095; p = 0.007) for BCLC stage B/C HCC patients who received hepatectomy. CONCLUSIONS: Compared with adjuvant PVC, neoadjuvant HAIC treatment was associated with better survival and fewer recurrences in HCC patients who received R0 resection at the intermediate to advanced stage. These results need to be further validated prospectively.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Fluoruracila/uso terapêutico , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Masculino , Terapia Neoadjuvante , Perfusão , Veia Porta , Estudos Retrospectivos , Resultado do TratamentoRESUMO
AIM: To study the treatment efficacy and survival of hepatic arterial infusion chemotherapy (HAIC) for patients with advanced hepatocellular carcinoma (HCC) and portal vein tumour thrombosis (PVTT) with compensated cirrhosis in comparison with sorafenib as the standard of care therapy versus best supportive care (BSC). MATERIALS AND METHODS: This case-control study included 91 patients with advanced HCC and PVTT divided into three groups: Group 1 20 treated with HAIC, (50 mg adriamycin and 50 mg cisplatin were infused in hepatic artery); Group 2, 42 patients treated with BSC; and Group 3, 29 patients treated with sorafenib. Patients were followed up for assessment and comparison of treatment outcome by modified Response Evaluation Criteria in Solid Tumours (mRECIST) and survival. RESULTS: There was no significant difference among the groups studied regarding baseline demographic and tumour characteristics. The majority of patients who received sorafenib therapy (82.8%) had stable disease. The response rate (complete response + partial response) was significantly better in the HAIC group. HAIC patients had the longest survival compared with the best supportive care and sorafenib groups, which was statistically significant (29.2 ± 21.8, 4.55 ± 11.41, and 11.52 ± 8.72 months respectively, p=0.007) CONCLUSION: HAIC is a safe procedure with a better response rate and longer survival than best supportive care or sorafenib for patients with advanced HCC and PVTT.
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Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/tratamento farmacológico , Veia Porta , Trombose Venosa/complicações , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos de Casos e Controles , Cisplatino/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/uso terapêutico , Feminino , Humanos , Infusões Intra-Arteriais , Masculino , Sorafenibe/uso terapêutico , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE/BACKGROUND: The purpose was to determine whether adding Pmab versus no Pmab to an adjuvant regimen of hepatic arterial infusion (HAI) of floxuridine (FUDR) plus systemic (SYS) leucovorin, fluorouracil, and irinotecan (FOLFIRI) improves 15-month recurrence-free survival for patients with RAS wild-type colorectal cancer. Secondary endpoints included overall survival, toxicity, and influence of predictive biomarkers. METHODS: This phase II trial randomized patients with KRAS wild-type resected colorectal liver metastases to adjuvant HAI FUDR + SYS FOLFIRI +/- Pmab (NCT01312857). Patients were stratified by clinical risk score and previous chemotherapy. Based on an exact binomial design, if one arm had ≥24 patients alive and disease-free at 15âmonths that regimen was considered promising for further investigation. RESULTS: Seventy-five patients were randomized. Patient characteristics and toxicity were not different in the 2 arms, except for rash in +Pmab arm. Grade 3/4 elevation in bilirubin or alkaline phosphatase did not differ in the 2 arms. Twenty-five (69%; 95% CI, 53-82) patients in the Pmab arm versus 18 (47%; 95% CI, 32-63) patients in the arm without Pmab were alive and recurrence-free at 15âmonths. Only the Pmab arm met the decision rule, while the other arm did not. After median follow-up of 56.6âmonths, 3-year recurrence-free survival was 57% (95% CI, 43-76) and 42% (95% CI, 29-61), and 3-year overall survival was 97% (95% CI, 90-99) and 91% (95% CI, 83-99), +/- Pmab, respectively. CONCLUSIONS: The addition of Pmab to HAI FUDR + SYS FOLFIRI showed promising activity without increased biliary toxicity and should be further investigated in a larger trial.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Panitumumabe/administração & dosagem , Adulto , Idoso , Camptotecina/uso terapêutico , Quimioterapia Adjuvante , Feminino , Floxuridina/administração & dosagem , Fluoruracila/uso terapêutico , Humanos , Infusões Intra-Arteriais , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas p21(ras)RESUMO
OBJECTIVE. The goal of this study was to evaluate radiologic and clinical factors associated with overall survival of advanced hepatocellular carcinoma treated with hepatic arterial infusion chemotherapy (HAIC). MATERIALS AND METHODS. This single-center retrospective study included 180 patients with advanced hepatocellular carcinoma who underwent HAIC with a 5-fluorouracil (250-500 mg/m2 for 5 hours) plus cisplatin (10-20 mg/m2 for 1-2 hours) regimen via an implantable port system. Survival curves were generated by the Kaplan-Meier method and compared by log-rank tests. Factors associated with overall survival were evaluated with Cox proportional hazard models. RESULTS. The median overall survival time was 7.6 months (95% CI, 6.1-9.1), and the objective response rate was 15%. In multivariate analysis, infiltrative tumor growth (hazard ratio [HR], 1.002; p = .03) and rimlike arterial enhancement (HR, 3.040; p < .001) were pretreatment radiologic factors associated with reduced overall survival. No early response to treatment (HR, 2.064-6.491) and higher Child-Pugh class (HR, 2.010-2.815) were strong prognostic factors of poor outcome. Treatment with three or more HAIC cycles (HR, 0.371; p = .001) and high-dose HAIC (HR, 0.447; p < .001) were favorable for increased overall survival. CONCLUSION. Infiltrative tumor growth and rimlike arterial enhancement in pre-treatment imaging studies were associated with poor prognosis, and better early radiologic response and preserved liver function reserve were strong indicators of prolonged survival. Recognizing these radiologic and clinical predictors may help optimize care of patients with hepatocellular carcinoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Antineoplásicos/uso terapêutico , Cisplatino/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Infusões Intra-Arteriais , Estimativa de Kaplan-Meier , Fígado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: We compared the clinical efficacies of hepatic arterial infusion chemotherapy (HAIC) vs. sorafenib as sequential maintenance therapy following liver-directed concurrent chemoradiotherapy (LD-CCRT) for locally advanced-stage hepatocellular carcinoma (HCC). METHODS: Patients undergoing HAIC with 5-fluorouracil and cisplatin (HAIC-maintain group, n = 151) or sorafenib (Sorafenib-maintain group, n = 37) after LD-CCRT were consecutively enrolled. The study endpoints were overall survival (OS), progression-free survival (PFS), and treatment response rates. RESULTS: The median OS among HAIC-maintain and Sorafenib-maintain groups were 15.9 and 24.3 months (p = 0.287), whereas the median PFS were 8.1 and 9.1 months (p = 0.651), respectively. During the planned treatments, the radiological objective response rate (54.3% vs. 64.9%; p = 0.246), and conversion rate to surgical resection or liver transplantation after successful down-staging (15.9% vs. 18.9%; p = 0.657) were comparable between the HAIC-maintain and Sorafenib-maintain groups. Similar results were found after the inverse probability of treatment weighting and propensity score-matching analyses. Regarding treatment-related adverse events, the HAIC-maintain group showed worse profiles in terms of leukopenia (all grades [p = 0.001] and grades 3 or 4 [p = 0.041]) and hypoalbuminemia (p = 0.001) than the Sorafenib-maintain group. CONCLUSIONS: The overall clinical efficacies between the sequential treatment of HAIC vs. sorafenib after LD-CCRT were comparable for locally advanced HCC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/patologia , Quimiorradioterapia/mortalidade , Neoplasias Hepáticas/patologia , Quimioterapia de Manutenção/mortalidade , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Cisplatino/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sorafenibe/administração & dosagem , Taxa de SobrevidaRESUMO
A male patient in his 70s underwent a right lobectomy because of a hepatocellular carcinoma(HCC)located in the right lobe(S6)of his liver. Eleven months after surgery, contrast-enhanced CT showed multiple masses in the residual liver, which were diagnosed as HCC recurrence. He was then treated with hepatic arterial infusion chemotherapy(HAIC). Ten months after the recurrence, the liver tumors progressed. Therefore, treatment was switched to sorafenib(400 mg/day orally)and HAIC(low-dose FP: 5-FU 250 mg plus CDDP 5 mg 5 days/week 4 weeks)sequential therapy. The patient received 2 cycles of sorafenib-HAIC sequential therapy for 11 months, and his liver tumors shrunk considerably. Unfortunately, 24 months after the recurrence of HCC, he died of respiratory failure. The cause of his death was officially determined to be primary lung cancer. An autopsy revealed that most tissues were necrotic, and only a small number of viable tumor cells were present in the liver tumors. This suggests that sorafenib-HAIC sequential therapy was significantly effective in targeting the multiple HCCs in this case.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/cirurgia , Artéria Hepática , Humanos , Infusões Intra-Arteriais , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Masculino , Recidiva Local de Neoplasia/tratamento farmacológico , Sorafenibe/uso terapêutico , Resultado do TratamentoRESUMO
Transarterial chemoembolization (TACE) is an image-guided locoregional therapy used for the treatment of patients with primary or secondary liver cancer. However, conventional TACE formulations are rapidly dissociated due to the instability of the emulsion, resulting in insufficient local drug concentrations in the target tumor. Methods: To overcome these limitations, a doxorubicin-loaded albumin nanoparticle-conjugated microbubble complex in an iodized oil emulsion (DOX-NPs-MB complex in Lipiodol) has been developed as a new ultrasound-triggered TACE formulation. Results: (1) Microbubbles enhanced therapeutic efficacy by effectively delivering doxorubicin- loaded nanoparticles into liver tumors via sonoporation under ultrasound irradiation (US+). (2) Microbubbles constituting the complex retained their function as an ultrasound contrast agent in Lipiodol. In a rabbit VX2 liver cancer model, the in vivo study of DOX-NPs-MB complex in Lipiodol (US+) decreased the viability of tumor more than the conventional TACE formulation, and in particular, effectively killed cancer cells in the tumor periphery. Conclusion: Incorporation of doxorubicin-loaded microbubble in the TACE formulation facilitated drug delivery to the tumor with real-time monitoring and enhanced the therapeutic efficacy of TACE. Thus, the enhanced TACE formulation may represent a new treatment strategy against liver cancer.