Arterial Infusion Of 5-fluorouracil Research Articles

Efficacy and safety of localized concurrent chemoradiation therapy and sorafenib sequential therapy in advanced hepatocellular carcinoma: A prospective phase II trial.

e15678 Background: Patients with advanced hepatocellular carcinoma (HCC) have a particularly poor prognosis of the median overall survival of less than 12 months. Even though sorafenib has been approved for treating advanced stage HCC, the unsatisfactory objective response rate still remain unresolved. In the current study, we aimed to evaluate the efficacy and safety of localized concurrent chemoradiotherapy (CCRT) followed by sequential sorafenib treatment for advanced hepatocellular carcinoma. Methods: This study is an ongoing, phase II trial. Patients with advanced HCC not amenable for curative treatments were eligible. In the course of radiotherapy for 5 weeks, hepatic arterial infusion of 5-fluorouracil (500mg/day) via implanted port was applied during the first 5 days and the last 5 days of radiotherapy. Four weeks after localized CCRT, sorafenib (400mg bid) was maintained. The primary endpoint was overall survival. Results: A total of 47 patients were enrolled. After the completion of localized CCRT, the objective response rate was 31.9%. During the overall treatment course, the objective response rate was 46.8% respectively. Overall, 7 patients (14.9%) underwent curative resection or transplantation after down-staging. The median overall survival was 18.4 months and the progression-free survival was 6.8 months. Adverse events were predictable and manageable with conservative care. Conclusions: Localized CCRT followed by sequential sorafenib treatment in patients with advanced HCC showed significant activity and good tolerability. Furthermore, such a treatment modality, when compared to the use of sorafenib alone, might provide the additional therapeutic benefit through initial tumor reduction, allowing curative treatment after down-staging in 14.9% of patients, Further randomized trial should be required to make the more robust evidence. Clinical trial information: NCT02425605.

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.

Complete remission of hepatocellular carcinoma with portal vein tumor thrombus and lymph node metastases by arterial infusion of 5-fluorouracil and interferon-α combination therapy following hepatic resection

We report two cases of hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) and lymph node (LN) metastases successfully treated by hepatic arterial infusion of 5-fluorouracil (5-FU) combined with systemic injection of interferon (IFN)-alpha following hepatic resection for the liver tumor. Complete remission was obtained. Case 1 was a 51-year-old man who had HCC in the right lobe of the liver with PVTT and multiple intrahepatic metastases. He also had abdominal and mediastinal LN metastases. Case 2 was a 53-year-old man who had diffuse-type HCC in the right lobe of the liver with PVTT and intrahepatic metastases. A chest computed tomography scan revealed lymph nodes enlarged to 1.0 cm from the mediastinum to the left supraclavicular space. Both patients underwent the hepatectomy to reduce the tumor volumes and remove the PVTT to relieve portal vein obstruction. Following the surgery, the patients underwent IFN-alpha/5-FU combination therapy. Three months after this combined therapy, tumor markers (both alpha-fetoprotein and protein induced by vitamin K absence or antagonist II) returned to the normal range and residual tumors in the liver disappeared. The patients are alive without any recurrence more than 1 year after initial treatment. IFN-alpha/5-FU combined therapy following hepatic resection is a promising modality for the treatment of advanced HCC with LN metastasis.

An experimental study on the pharmacokinetics of 5-fluorouracil regional chemotherapy for pancreatic cancer.

Recently a few centers reported promising results of regional intra-arterial chemotherapy for pancreatic cancer. However, the detailed pharmacokinetics and the side effects of anticancer agents remain unclear. Catheters were introduced into the gastroduodenal artery and the splenic artery of dogs. In group I, arterial infusion of 5-fluorouracil (5-FU) was performed over 10 minutes. In group II, 5-FU was infused systemically. In group III, an intra-arterial infusion was repeated weekly three times. Blood samples and liver and pancreas tissue samples were obtained to determine 5-FU levels. In a subset of each group, the pancreas, duodenum, and liver were excised for histological analyses. Immediately after the infusion of 5-FU, the portal level in group I was higher than that in group II. However, the mean systemic level in group I was lower than in group II. The mean tissue concentration in the pancreas in group I was significantly higher than that of group II. Histological examination revealed no microscopic alterations after treatment in all groups, including group III. This fundamental study suggested that intra-arterial chemotherapy of 5-FU for pancreatic cancer allows higher regional drug delivery without adverse effects on normal regions of the pancreas, the duodenum, and the liver.

A 10-year survivor with unresectable hepatic metastases from sigmoid colon carcinoma treated with regional chemotherapy

We treated a man with unresectable hepatic metastases from sigmoid colon carcinoma who has since survived for more than 10 years. A sigmoidectomy with lymph node dissection was performed and a continuous hepatic arterial infusion of 5-fluorouracil (5-FU) with intermittent infusion of mitomycin C (MMC) was administered for about 3 months after this operation. The total doses of 5-FU and MMC were 16 g and 84 mg, respectively. Tegafur also was administered orally at a dose of 600 mg/day for about 8 months. The carcinoembryonic antigen (CEA) level (which had reached 4,409 ng/ml preoperatively) normalized 4 months after surgery, and still remains normal. Very few patients with unresectable hepatic metastases survive for 5 or more years. However, regional chemotherapy can be effective in some patients.

Arterial changes during treatment with intrahepatic arterial infusion of 5-fluorouracil.

Changes in the liver arteries ranging from minimal irregularities in occlusions and development of aneurysms were investigated in 27 patients who received intra-arterial infusion of 5-FU in the hepatic artery. Variations in the arterial caliber peripheral to the hilum of the liver were noted in 13 of the patients. Further investigation of such arterial changes may be important in controlling the growth of liver metastases.

Arterial infusion of 5-fluorouracil as a treatment for carcinoma of the prostate.

Arterial infusion of 5-fluorouracil as a treatment for carcinoma of the prostate.

The continuous arterial infusion of 5-fluorouracil as a therapeutic adjunct in the treatment of advanced carcinoma of the bladder and prostate. A preliminary report.

Twenty-two patients have been treated with the intra-arterial infusion of 5-fluorouracil followed by megavoltage radiation. Nine patients with carcinoma of the prostate completed the protocol. All of these patients responded to 5-fluorouracil. This was documented by a decrease in tumor size, improvement in IVP and cystograms, lowering of specific acid phosphatase, control of bony metastasis, and a marked improvement in symptoms. Six of the patients are alive and asymptomatic today. Three patients have no clinical or microscopic evidence of retained disease. The mean survival is 21 months with a range of 13 to 31 months. Six of ten patients with bladder carcinoma responded to the 5-fluorouracil. This was documented by a marked reduction in tumor size in all patients and complete destruction of the tumor in four patients. Four of the patients are alive and microscopically free of their disease. The mean survival is 25 months with a range of 19 to 34 months. These results suggest that this therapeutic modality should be continued at our institution for advanced carcinomas of the bladder and prostate. In order that a more complete evaluation of the protocol be obtained, other institutions will have to participate in an identical treatment program.