Safety Of Hepatic Arterial Infusion Research Articles

A randomized phase II trial of hepatic arterial infusion of oxaliplatin plus raltitrexed versus oxaliplatin plus 5-fluorouracil for unresectable colorectal cancer liver metastases.

BackgroundThe purpose was to compare the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin plus raltitrexed (TOMOX) to those of oxaliplatin plus 5-fluorouracil (FOLFOX) for unresectable colorectal cancer liver metastases (CRCLM).MethodsPatients with unresectable CRCLM were randomly assigned to receive HAI of TOMOX or FOLFOX. The primary end points were progression-free survival (PFS) measured from the date of randomisation until the date of disease progression and objective response rate (ORR). The secondary end points were overall survival (OS) measured from the date of randomisation until the date of death from any cause, disease control rate (DCR), and adverse events.Results113 patients were randomly assigned. With a median follow-up of 39.5 months, the PFS was 5.8 months [95% CI, 4.838–6.762]) and 4.6 months [95% CI, 3.419–5.781; P = 0.840], and the median OS was 17.6 months [95% CI, 13.828–21.372] and 13.1 months [95% CI, 11.215–14.985; P = 0.178] for the FOLFOX and TOMOX arm, respectively. The ORR were 26.1% vs 22.4% and DCR were 80.4% vs 71.4% in the FOLFOX and TOMOX arms. The most common severe adverse event was elevation of liver enzymes and pain, which did not differ in the two arms.ConclusionHAI chemotherapy was effective for unresectable CRCLM. HAI of FOLFOX has similar efficacy to TOMOX, and HAI of TOMOX had shorter arterial infusion time.Clinical Trial Registration https://clinicaltrials.gov/, identifier NCT02557490.

Hepatic Artery Infusion Pump Combined With Systemic Chemotherapy for Patients With Liver Metastases From Breast Carcinoma.

Background: When liver metastasis in patients with breast cancer is diagnosed, treatment is generally palliative and usually consists of systemic therapies only. This study aimed to evaluate the efficacy and safety of hepatic arterial infusion (HAI) combined with systemic chemotherapy in patients with breast carcinoma liver metastases (BCLM). Methods: From January 2012 to December 2019, HAI catheter systems were implanted under the guide of digital subtract angiography (DSA) in 19 patients with BCLM. All patients received systemic chemotherapy and HAI gemcitabine plus floxuridine (FUDR). Methods: The overall response rate (ORR) of intrahepatic lesions was 73.7%, including 2 patients (10.5%) with complete remission (CR) and 12 patients (63.2%) with partial remission (PR). Additionally, we found that young patients (age < 55 years) had a higher ORR than the older (100% vs 44.4%, P = .011). The median overall survival (mOS) was 13.1 months. Kaplan-Meier survival curves demonstrated that the mOS was not significantly different between patients with < 9 intrahepatic lesions and those with ≥ 9 lesions (13.7 months vs 10.9 months, P = .225). The mOS was 14.3 and 10.6 months for patients without extrahepatic metastases and with extrahepatic metastases, respectively (P = .016). None of the patients had grade 4 toxicity. The grade 3 toxicities included leucopenia, neutropenia and diarrhea. Conclusions: HAI gemcitabine plus FUDR combined with systemic chemotherapy is effective in achieving a high local response and prolonging mOS for patients with BCLM and is associated with a relatively low rate of toxicity.

Hepatic arterial infusion of oxaliplatin plus raltitrexed in patients with intermediate and advanced stage hepatocellular carcinoma: A phase II, single-arm, prospective study

PurposeTo investigate the efficacy and safety of hepatic arterial infusion (HAI) of oxaliplatin plus raltitrexed in patients with intermediate stage and advanced stage hepatocellular carcinoma (HCC). MethodsIn this phase II, single-arm clinical trial, we enrolled patients aged 18–70 years with intermediate stage and advanced stage HCC, which included patients with HCC at Barcelona Clinic Liver Cancer (BCLC) stage B who experienced transcatheter arterial chemoembolization failure/refractoriness, and those with BCLC stage C with portal vein invasion. We performed HAI with oxaliplatin and raltitrexed. Treatment was repeated every 3 weeks and was discontinued either because of disease progression, unacceptable toxicity levels, or refusal of further treatment. We used Simon's two-stage design. The primary end-point was the objective response rate in accordance with the Response Evaluation Criteria in Solid Tumours. ResultsFifty-one patients were screened between January 5, 2018 and August 7, 2019. Of these, 39 patients (34 men and 5 women; median age, 53 years) were enrolled and included in the intention-to-treat population. Objective response was achieved in 18 (51.4%) of 35 patients in the per-protocol population and in 18 (46.2%) of 39 patients in the intention-to-treat population. Treatment-related grade IV adverse events or deaths were not reported, and the observed grade III adverse events were elevated aspartate aminotransferase levels (5 [12.8%]), elevated alanine aminotransferase levels (1 [2.6%]), leukopenia (1 [2.6%]), thrombocytopaenia (1 [2.6%]) and abdominal infection (1 [2.6%]). ConclusionHAI of oxaliplatin plus raltitrexed showed promising efficacy and acceptable toxicity levels in patients with intermediate and advanced stage HCC, and further evaluation is warranted.

Hepatic arterial infusion of oxaliplatin plus raltitrexed in patients with unresectable hepatocellular carcinoma (HAIROX): A phase II, single-arm, prospective study.

4574 Background: Chemoembolisation and oral sorafenib are the recommended treatment for unresectable hepatocellular carcinoma (HCC); however, some patients respond poorly to these. Hepatic arterial infusion (HAI) chemotherapy may have potential benefit in these patients. We aimed to investigate the efficacy and safety of HAI of oxaliplatin plus raltitrexed in patients with unresectable HCC. Methods: In this phase II, single-arm clinical trial, we enrolled patients aged 18–70 years with unresectable HCC at the Fujian Cancer Hospital (China). We performed HAI with oxaliplatin (100 mg/m2 for 4 hours) and raltitrexed (3 mg/m2 for 1 hour). Treatment was repeated every 3 weeks and was discontinued either because of disease progression, unacceptable toxicity levels, or refusal of further treatment. We used Simon’s two-stage design. The primary endpoint was the objective response rate according to the Response Evaluation Criteria in Solid Tumors version 1.1. Results: Fifty-one patients were screened between January 5, 2018 and August 7, 2019. Of these, 39 patients (34 men and 5 women; median age, 53 years) were enrolled and included in the intention-to-treat population. Objective response was achieved in 18 (51.4%) of 35 patients in the per-protocol population and in 18 (46.2%) of 39 patients in the intention-to-treat population. Treatment-related grade 4 adverse events or deaths were not reported, and the observed grade 3 adverse events were elevated aspartate aminotransferase levels (5[12.8%]), elevated alanine aminotransferase levels (1 [2.6%]), leukopenia (1 [2.6%]), thrombocytopenia (1 [2.6%]), and abdominal infection (1 [2.6%]). Conclusions: HAI of oxaliplatin plus raltitrexed showed promising efficacy and acceptable toxicity levels in patients unresectable HCC, and further evaluation is warranted. Clinical trial information: ChiCTR-OOC-17014182 . [Table: see text]

Hepatic Arterial Infusion Combined with Systemic Chemotherapy for Patients with Extensive Liver Metastases from Gastric Cancer.

PurposeLiver metastases in patients with gastric cancer often indicate poor prognosis. Once liver metastases are extensive, it is difficult to achieve disease control by using systemic chemotherapy alone. The purpose of this study was to evaluate the effect and safety of hepatic arterial infusion (HAI) combined with systemic chemotherapy on extensive liver metastases from gastric cancer.Patients and MethodsBetween 2012 and 2019, 21 patients with extensive liver metastases from gastric cancer (LMGC) were enrolled in our study. Liver metastases were identified as unresectable and a major factor affecting prognosis mainly based on size and number of intrahepatic lesions. All patients received systemic chemotherapy with S-1 and HAI oxaliplatin plus floxuridine (FUDR).ResultsLiver metastases in 16 patients (76.2%) were evaluated as H3. The overall response rate was 76.2% (9.5% complete response). Intrahepatic and extrahepatic median progression-free survival times were 9.5 and 5.2 months, respectively. Median survival time (MST) was 12.3 months. All patients did not have the toxicity of grade 4. Grade 3 toxic effects included bone marrow suppression (14.3%) and diarrhea (9.5%). The other treatment-related toxicities were mild and reversible.ConclusionHAI combined with systemic chemotherapy for extensive LMGC seems to be safe and effective, which achieves a high-local response and may contribute to long survival time for patients.

Hepatic Arterial Infusion of Oxaliplatin Plus Raltitrexed in Patients with Intermediate- and Advanced-Stage Hepatocellular Carcinoma (HAIROX): A Phase II, Single-Arm, Prospective Study

Background: Hepatic arterial infusion of oxaliplatin plus fluorouracil could improve the outcomes of patients with advanced hepatocellular carcinoma. Fluorouracil is inconvenient for arterial infusion because it requires prolonged infusion. Conversely, raltitrexed, another antimetabolic drug, could be used in short infusions. We aimed to investigate the efficacy and safety of hepatic arterial infusion of oxaliplatin plus raltitrexed in patients with intermediate- and advanced-stage hepatocellular carcinoma. Patients and methods: We enrolled patients aged 18-70 years with intermediate-stage hepatocellular carcinoma with chemoembolisation failure/refractoriness and advanced-stage hepatocellular carcinoma with portal vein invasion. We performed hepatic arterial infusion with oxaliplatin (100 mg/m2 infusion for 4 hours) and raltitrexed (3 mg/m2 for 1 hour). Treatment was repeated every 3 weeks and was discontinued either because disease progression did not allow further treatment, toxicity levels were unacceptable, or the patient refused further treatment. The primary endpoint was the objective response rate according to the Response Evaluation Criteria in Solid Tumors version 1.1. Results: Fifty-one patients were screened between 5 January, 2018 and 7 August, 2019. Of these, 39 patients were enrolled and included in the intention-to-treat population. Objective response was achieved in 18 (51.4%) of 35 patients in the per-protocol population and in 18 (46.2%) of 39 patients in the intention-to-treat population. There were no reports of treatment-related grade 4 adverse events or deaths, and the observed grade 3 adverse events were elevated aspartate aminotransferase levels (5[12.8%]), elevated alanine aminotransferase levels (1 [2.6%]), leukopenia (1 [2.6%]), thrombocytopenia (1 [2.6%]), and abdominal infection (1 [2.6%]). Conclusion: Hepatic arterial infusion of oxaliplatin plus raltitrexed showed promising efficacy and acceptable toxicity levels in patients with intermediate- and advanced-stage hepatocellular carcinoma, and a multi-centre, phase III trial is expected. Clinical Trial Registration: This study is registered with www.chictr.org.cn, number ChiCTR-OOC-17014182. Funding Statement: This work was supported by the Guiding Project of Science and Technology Planning Project in Fujian Province, China (grant number 2019Y0060). Declaration of Interests: The authors have declared no conflicts of interest. Ethical Approval Statement: The trial was approved by the Ethics Committee of Fujian Cancer Hospital and was performed according to the Declaration of Helsinki. All patients involved in the trial provided written informed consent.

Liver regeneration therapy through the hepatic artery-infusion of cultured bone marrow cells in a canine liver fibrosis model.

BackgroundWe previously reported regenerative therapies for decompensated cirrhosis based on peripheral venous drip infusion using non-cultured whole bone marrow (BM) cells, or the less invasive cultured BM-derived mesenchymal stem cells (BMSCs). Here, we assessed the efficacy and safety of hepatic arterial infusion using cultured autologous BMSCs, comparing it with peripheral infusion, using our established canine liver fibrosis model.MethodsCanine BM cells were harvested and cultured, and the resultant BMSCs were returned to carbon tetrachloride (CCl4)-induced liver cirrhosis model canines via either a peripheral vein (Vein group) or hepatic artery (Artery group). A variety of assays were performed before and 4, 8, and 12 weeks after BMSC infusion, and liver fibrosis and indocyanine green (ICG) half-life (t1/2) were compared to those in a control group that received CCl4 but not BMSCs. The safety of this approach was evaluated by contrast-enhanced computed tomography (CT) and serial blood examinations after infusion.ResultsFour weeks after infusing BMSCs, a significant improvement was observed in the Vein group (n = 8) compared to outcome in the Control group (n = 10), along with a decrease in ICG t1/2. In the Artery group (n = 4), ICG t1/2 was significantly shorter than that in the Vein group at 8 weeks (Δt1/2: −3.8 ± 1.7 min vs. +0.4 ± 2.4 min; p < 0.01) and 12 weeks (Δt1/2: −4.2 ± 1.7 min vs. +0.4 ± 2.7 min; p < 0.01) after BMSC administration. Post-infusion contrast-enhanced CT showed no liver infarction, and blood tests showed no elevations in either serum lactate dehydrogenase concentrations or hypercoagulability.ConclusionsWe confirmed the efficacy and safety of the hepatic arterial infusion of cultured autologous BMSCs using a canine model, thereby providing non-clinical proof-of-concept.

Clinical effect and safety of hepatic arterial infusion of cinobufotalin injection combined with lipiodol chemoembolization in treatment of Barcelona Clinic Liver Cancer stage C primary liver cancer

Clinical effect and safety of hepatic arterial infusion of cinobufotalin injection combined with lipiodol chemoembolization in treatment of Barcelona Clinic Liver Cancer stage C primary liver cancer

The efficacy and safety of hepatic arterial infusion of oxaliplatin plus intravenous irinotecan, leucovorin and fluorouracil in colorectal cancer with inoperable hepatic metastasis

Hepatic arterial infusion (HAI) was evaluated for different drugs to treat hepatic metastasis from colorectal cancer (CRC). Combination treatment with 5-fluorouracil (5-FU), leucovorin, oxaliplatin and irinotecan (FOLFOXIRI) is effective for CRC. A phase II study was conducted to evaluate concomitant HAI administration of oxaliplatin and intravenous leucovorin, 5-FU and irinotecan (FOLFIRI) for patients with inoperable liver metastasis, which had chemotherapy with oxaliplatin (OX) 85 mg/m2 HAI plus systemic intravenous chemotherapy [leucovorin 200 mg/m2, 5-FU 2400 mg/m2 and irinotecan (IRI) 160 mg/m2 in 48 hours]. We treated 24 patients. Neutropaenia was the most frequent toxicity. The main HAI-related toxicity was pain. Two patients (8%) obtained complete response and 17 patients (70%) partial response, giving an objective response rate of 78%. Median follow-up was 22.8 months, and median overall and disease-free survival times were 29 and 20 months, respectively. Therefore, OX HAI and intravenous FOLFIRI is feasible and effective in patients with metastatic CRC.

Unresectable Colorectal Liver Metastases: The Safety and Efficacy of Conversion Therapy Using Hepatic Arterial Infusion Immunochemotherapy with 5‐Fluorouracil and Polyethylene Glycol‐Interferon α‐2a

Hepatic arterial infusion (HAI) or systemic chemotherapy has been used to treat unresectable colorectal liver metastases. The prognosis of the disease in recent years has been improved because chemotherapy is performed before hepatectomy to reduce tumor size (conversion therapy). The purpose of this study was to investigate the safety and efficacy of conversion therapy following HAI immunochemotherapy. Hepatic arterial infusion of 5-fluorouracil (5-FU)/polyethylene glycol (PEG)-IFNα-2a was performed in 21 patients. The primary endpoint was the safety of HAI and hepatectomy. The secondary endpoints were response rate, rate of conversion to hepatectomy, survival rate, and prognostic factors. With regard to side effects, drugs were discontinued temporarily in one patient because of a decrease in white blood cell count; however, other patients continued chemotherapy. The response rate with HAI was 61.9 %, and the conversion rate was 38.1 %. Hepatectomy was completed successfully without mortality. Median progression-free survival (PFS) was 11.5 months (with and without conversion, 16.7 and 4.8 months, respectively; p = 0.021). Median overall survival was 34.6 months (with and without conversion, 48.4 and 26.6 months, respectively; p = 0.003). Prognosis was poor when the number of metastatic tumors was ≥10 [PFS: hazard ratio (HR) 32.21, p = 0.003; overall survival (OS): HR 9.13, p = 0.07], but prognosis improved after hepatectomy (OS: HR 0.08, p = 0.09). Hepatic arterial infusion immunochemotherapy with 5-FU/PEG-IFNα-2a was performed safely without major side effects. Prognosis is expected to improve after successful conversion to hepatectomy.

Hepatic Arterial Infusion with Irinotecan, Oxaliplatin, and Floxuridine plus Systemic Chemotherapy as First-Line Treatment of Unresectable Liver Metastases from Colorectal Cancer

Background: The aim of this study was to evaluate the therapeutic efficacy and safety of hepatic arterial infusion (HAI) with irinotecan, oxaliplatin, and floxuridine as a firstline treatment in patients with unresectable liver metastases of colorectal cancer (CRC). Patients and Methods: Individual patients were treated with irinotecan (120 mg/m²), oxaliplatin (100 mg/m²), and floxuridine (500 mg/m²) via tumorsupplying arteries. Intravenous leucovorin (200 mg/day) and floxuridine (300 mg/m²/day) were given on days 1–3 after the procedure. The therapeutic courses were repeated every 4–8 weeks. Tumor responses, overall survival, and the time to tumor progression were observed. Results: 204 cumulative cycles of chemotherapy were performed for 31 patients (median 7.0). 19 patients achieved a partial response; in 10 patients the disease stabilized, and in 2 patients the disease progressed, producing an overall response rate of 61.3%. The median survival time was 24.8 months, and the median time to tumor progression was 10.1 months. Frequencies of grade 3–4 neutropenia, diarrhea, elevation of serum bilirubin, elevation of serum transaminases, and vomiting were 6.5, 9.7, 3.2, 19.4, and 90.3%, respectively. Conclusion: This triplecombination chemotherapy as firstline treatment through HAI was well tolerated and effective in patients with unresectable liver metastases of CRC.

Safety and Optimal Management of Hepatic Arterial Infusion Chemotherapy After Pancreatectomy for Pancreatobiliary Cancer

The purpose of this study was to assess the safety of hepatic arterial infusion (HAI) chemotherapy after pancreatectomy for pancreatobiliary cancer. The study subjects comprised 51 patients treated with HAI chemotherapy after pancreatectomy: 31 patients had undergone pancreaticoduodenectomy or total pancreatectomy and 20 patients had undergone distal pancreatectomy. HAI chemotherapy was performed for the prevention of liver metastasis in 42 patients and for the treatment of metastases in nine patients. HAI chemotherapy consisted of 5-fluorouracil administered at 1000 mg/m(2)/wk. After each cycle of chemotherapy, the patency of the hepatic artery and complications were evaluated using digital subtraction angiography and CT arteriography via the catheter-port system. Placement of the catheter-port system was successful in all patients. Hepatic arterial occlusion and severe asymptomatic hepatic artery stenosis were observed in one patient (2%) and 10 patients (19.6%), respectively. The hepatic arterial patency rate tended to be lower in the group who underwent pancreaticoduodenectomy or total pancreatectomy (71%) than in the group who underwent distal pancreatectomy (90%), although the difference was not significant (p = 0.107). Four asymptomatic patients with hepatic artery stenosis restarted HAI chemotherapy after a 4-week withdrawal of treatment. In three patients (5.9%), all of whom had undergone pancreaticoduodenectomy, liver abscess or biloma developed synchronously with asymptomatic hepatic artery stenosis. All three cases were cured by percutaneous abscess drainage or conservative management. The tumor response rate in the treatment of liver metastases was 44.4%. The hepatic recurrence rate with adjuvant therapy was 7.1%. Our findings suggest that HAI chemotherapy after pancreatectomy is feasible and tolerable, although caution is required particularly after pancreaticoduodenectomy or after total pancreatectomy.

Efficacy and Safety of Hepatic Arterial Infusion of Fluorouracil with Leucovorin as Salvage Treatment for Refractory Liver Metastases from Colorectal Cancer

Background/AimsLimited options remain for patients with metastatic colorectal cancer (CRC) after failure of standard systemic chemotherapy. Readministration of chemotherapeutic agents by hepatic arterial infusion (HAI) has the rationale of providing higher concentrations of chemotherapeutic agents to hepatic metastases. The present study was conducted to evaluate the efficacy and safety of HAI of fluorouracil with leucovorin (HAI 5-FU/LV) for patients with liver metastases from CRC.MethodsFourteen patients with liver metastases from CRC who received HAI 5-FU/LV after failure of systemic chemotherapy containing fluorouracil and leucovorin were identified and their medical records were reviewed.ResultsOf 10 patients evaluable for response, one partial response, six stable disease, and three progressive disease were reported. Additionally, the overall response and disease control rates were 7% and 50%, respectively. The median time to progression was 4.3 months (range, 2.9 to 5.6), to hepatic progression was 5.8 months (range, 4.7 to 6.9), and to extrahepatic progression was 5.8 months (range, 2.3 to 9.2). No grade 3/4 hematologic toxicities occurred and one case of abdominal pain and two cases of oral mucositis were the only grade 3 nonhematologic toxicities. Catheter-related complications occurred in three patients: one thrombosis, one infection, and one displacement.ConclusionsHAI 5-FU/LV was well tolerated and showed modest efficacy for patients with liver metastases from refractory CRC. Readministration of previously used chemotherapeutic agents via the hepatic artery could be an effective salvage option and warrants further investigation in a prospective trial.

Study of hepatic arterial infusion of Endostar combined with TACE on advanced hepatocellular carcinoma

Objective To study the efficacy and safety of hepatic arterial infusion of Endostatin (YH-16, Endostar), combined with transcatheter arterial chemoembolization (TACE) on advanced hepatocellular carcinoma.