Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-two patients with hepatic colorectal metastases had Infusaid pumps implanted for hepatic artery infusion chemotherapy, or HAIC. Prior to pump placement, 19 of the 22 patients received percutaneous HAIC with 5-fluorouracil and citrovorum factor. Floxuridine, 0.2 mg/kg/d, was administered via the Infusaid pump and was alternated with saline solution every 2 weeks. HAIC responsiveness was defined as a 50% or greater reduction in the sum of all diameters of measured lesions on computerized tomography scans and no evidence of extra-hepatic tumor. Nine patients (41%) had a favorable response to HAIC; four (18%) had a partial response to percutaneous HAIC and five (23%) were considered pump responders. All responders had pretreatment liver replacement of less than 50%. The mean survival after pump placement was 13.6 months for responders and 11.1 months for non-responders. Although there were no operative deaths, the morbidity rate was 36%, and 31% of patients manifested significant chemotherapy toxicity. While toxicity is not insignificant and there is no survival benefit, the Infusaid pump is a reliable drug delivery system for HAIC, and may result in regression of colorectal liver metastases in patients with less than 50% hepatic replacement.
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PMID:Hepatic artery infusion chemotherapy for colorectal liver metastases. 225 76

During a five year period, 69 patients were treated for carcinoma of the liver (seven primary tumors and 62 metastatic tumors) with 5-fluorodeoxyuridine (5-FUDR) administered through a hepatic artery (n = 62) or portal vein (n = 3) implantable infusion pump. Ten patients proved to have previously unsuspected extrahepatic nodal metastases at laparotomy for pump insertion. 5-FUDR was given in 14 day cycles for three months. At the end of that period and at three month intervals thereafter (mean follow-up time of 18 months, a range of one to 60 months), patients were evaluated with roentgenograms of the chest, liver function tests, carcinoembryonic antigen levels, radionuclide scans and computed tomography. Thirty-five patients had a partial response, nine had stabilization of the disease and 25 had progression of the disease (five during therapy, who were given mitomycin C). Median regression was 6.8 months (a range of three to 18 months). Six of the 35 partial responders, three of the nine patients with stabilization and ten of the 25 patients with progression had extrahepatic visceral disease. Survival time averaged 18.4 months (a range of five to 60 months) for the partial responders, 12.6 months (a range of two to 40 months) for patients with stabilization and seven months (a range of one to 17 months) for those with progression of the disease.
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PMID:Chemoinfusion of the hepatic artery for metastases to the liver. 252 84

Loco-regional intra-arterial chemotherapy of hepatic metastases from colo-rectal cancer is one of the most effective non-surgical treatments in this clinical situation. In our experience of 58 cases treated during 3 years, in a non randomized study by either: 1) discontinuous perfusion of 5FU (using a subcutaneous access) or 2) by continuous infusion of FUDR (using an implantable pump), we observed an objective response rate of 52% and 53% with a 1 year survival of 73% and 90%, respectively. This technique, however, is limited in its application by loco-regional complications and in its long term efficacy by the development of extrahepatic metastases. The proof of its efficacy in terms of survival prolongation, is being studied within the framework of a prospective randomized trial with a control group.
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PMID:Intra-arterial hepatic chemotherapy for metastatic liver from colo-rectal carcinoma origin. 252 63

In 1983, the Northern California Oncology Group (NCOG) instituted a randomized trial of intravenous (IV) versus intraarterial (IA) floxuridine (FUDR) administered via an implantable pump for patients with colorectal cancer metastatic to the liver. The study objectives were to compare the hepatic response rate, time to hepatic progression, and toxicity for the two treatment arms. The study design, which allowed patients failing IV FUDR to crossover to the IA arm, prevents a meaningful comparative analysis of survival. Patients with liver-only metastases (N = 143) were randomized, 76 to the IV arm and 67 to the IA arm, and 115 patients (65 IV, 50 IA) were fully evaluable. Of the 65 patients in the IV arm, 28 crossed over to IA treatment after failing IV FUDR. The dose-limiting toxicity of IV FUDR was diarrhea, whereas biliary toxicity limited both the dose and duration of IA FUDR therapy. Of the first 25 patients treated with IA FUDR at a dose of .3 mg/kg/day, 10 developed radiographically evident biliary strictures, and three developed permanent jaundice. With reduction of the initial IA FUDR dose to .2 mg/kg/day, and adoption of a policy of early dosage reduction, treatment interruption, or termination of therapy for persistent elevations in alkaline phosphatase, only two further cases of serious biliary toxicity occurred. However, 26 of the 50 IA FUDR patients ultimately had therapy terminated because of drug toxicity rather than disease progression. When compared with systemic infusion, infusion into the hepatic artery greatly enhanced the antitumor activity of FUDR against colorectal liver metastases. Although biliary toxicity is the most serious limitation of this form of therapy, biliary stricture and jaundice usually can be averted through careful monitoring of liver enzymes and early dosage reduction.
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PMID:A randomized trial of continuous intravenous versus hepatic intraarterial floxuridine in patients with colorectal cancer metastatic to the liver: the Northern California Oncology Group trial. 253 Mar 17

Iododeoxyuridine (IdUrd) was administered as a continuous infusion for 14 days to patients with glioblastoma and sarcoma, and for 3 days to patients with metastatic colorectal carcinoma. In the first group, the maximum incorporation of IdUrd into DNA was determined, taking granulocytes as parameter. In the second group, selective incorporation into DNA of normal liver and hepatic metastases of colorectal cancer was investigated. The highest dose of 675 mg/sq.m./day for 14 days produced IdUrd plasma concentrations of 1.8 +/- 0.3 microM, and a substitution of dThd by IdUrd in the range of 7.1-11.7%. Coadministration of fluorodeoxyuridine did not show significant enhancement of IdUrd-incorporation in granulocytes. Three-day intravenous infusions of IdUrd 1000 mg/sq.m./day produced 1.7-4.5% IdUrd-incorporation in hepatic metastases. Three-day intraarterial infusions (hepatic artery) produced 3.8-10.5% dThd-replacement, whereas, in 9/10 patients this was less than 1% in normal liver. In tumor tissue there was a trend towards FdUrd-modulated enhancement of IdUrd-incorporation, although there was considerable scatter. Cell kinetic studies revealed that IdUrd-incorporation in monocytes and granulocytes was very similar. In lymphocytes, a much lower fraction incorporated IdUrd. Liver tumor contained a considerably higher fraction of IdUrd-labeled cells, compared with normal liver. Potential doubling times for the tumors were estimated to be 10 days.
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PMID:Iododeoxyuridine (IdUrd) incorporation into DNA of human hematopoietic cells, normal liver and hepatic metastases in man: as a radiosensitizer and as a marker for cell kinetic studies. 271 75

By far the majority of 54 patients suffering from hepatic metastases due to colorectal primaries developed obliterations of the arterial vascular bed when being submitted to regional chemotherapy with FUDR. In addition, about 25% exhibited obstructive jaundice in the course of severe sclerosing cholangitis. Either effect, which can be detected by radiological procedures, has to be referred to irritating activities of the chemotherapeutic drug used.
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PMID:[Biliary and arterial obstructive processes in regional chemotherapy with FUDR]. 284 77

Toxicities and complications were prospectively analyzed in patients with liver metastases receiving hepatic intra-arterial (IA) and systemic intravenous (IV) floxuridine (FUDR) with the Infusaid (Intermedics-Infusaid Corp., Norwood, MA) implantable pump. Among 55 patients treated with IA FUDR (0.3-0.1 mg/kg/day X 14, every 28 days), elevations in liver enzyme values, not attributable to disease progression, developed in 96% of patients. Serious biliary toxicity occurred in 31 patients (56%). In 16, biliary sclerosis was documented radiographically and was diagnosed clinically in 15 additional patients. Ten patients were hospitalized for biliary toxicity, including five who required cholecystectomy for acalculous cholecystitis. Because of the high reported incidence of serious gastroduodenal toxicity after IA FUDR infusion, our procedure for hepatic arterial cannulation was designed to eliminate misperfusion of the stomach and duodenum with drug; none of our patients experienced FUDR-associated gastroduodenal ulceration or bleeding. Cyclic IV FUDR (0.05-0.15 mg/kg/day X 14, every 28 days) was administered to 31 participants of the Northern California Oncology Group trial (3L-82-1) of IV versus IA FUDR. Dose-limiting toxicity was diarrhea. Serious toxicities were: protracted diarrhea (three), dermatitis (two), tear duct stenosis (two), and stomatitis (two). Three patients were hospitalized for toxicity. No hematologic or biliary toxicity occurred. The optimal route for treatment of hepatic metastases with continuous FUDR infusion has not yet been established. Systemic IV infusion has low morbidity, but preliminary response data need to be substantiated in controlled clinical trials before there can be widespread clinical application. High response rates for IA infusion have been previously documented. Morbidity due to acalculous cholecystitis and gastroduodenal ulceration can now be avoided. Despite significant progress in characterization of hepatobiliary toxicity, it remains dose-limiting. Continuous IA FUDR infusion should remain under the aegis of dedicated treatment centers until standardized protocols with diminished toxicity are established.
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PMID:Toxicities and complications of implanted pump hepatic arterial and intravenous floxuridine infusion. 293 42

A pilot study was designed to evaluate the efficacy of high-dose FUDR administered through the hepatic artery for the treatment of cancer involving the liver. Three dose schedules were used beginning with a dose of 0.5 mg FUDR/kg/day for 2 weeks followed by normal saline infusion for 2 weeks (schedule A). Elevation of serum bilirubin was the sole indication to deescalate to schedule B (0.3 mg FUDR/kg/day for two weeks followed by saline infusion for 4 weeks). Tolerance to this schedule escalated the patient to schedule C (0.5 mg FUDR/kg/day for 2 weeks followed by normal saline infusion for 4 weeks). Eighteen patients were treated, sixteen with metastatic colon cancer, one with metastatic leiomyosarcoma, and one with hepatoma. The patient with hepatoma developed progressive disease after one cycle of therapy. Of the 17 patients with metastatic cancer only 5 patients failed therapy yielding a 70% response rate. High-dose FUDR was well tolerated with only six patients requiring deescalation to schedule B. Elevation of alkaline phosphatase and glutamic oxaloacetic transaminase was universal. Two patients developed peptic ulceration. Sclerosing cholangitis was not observed. We conclude that high-dose FUDR administered through the hepatic artery is as safe as conventional dose infusion therapy but probably not more effective. The safety of high-dose FUDR infusion therapy suggests that sclerosing cholangitis is association with hepatic arterial infusion therapy is not related to the FUDR dose.
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PMID:Good tolerance to high-dose hepatic arterial infusion therapy. 294 73

Comparative in vitro drug testing was performed in 72 of 183 surgically removed human colorectal cancer specimens (34 primary lesions, 38 metastases). In 10 of these tumors, comparative dose-response curves were obtained. Given a greater than or equal to 70% ICF (inhibition of colony formation) as threshold for in vitro sensitivity, 5-FU was active in 16/62 specimens, and FUDR in 14/62. Significantly discordant sensitivity results were observed in 8/62 tests, 5-FU being the more active agent in 5 of these cases. These data are supported by the finding of 3 considerably differing dose-response curves in 10 additional comparative studies of human primary tumors.
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PMID:Comparison of 5-FU versus FUDR activity in human colorectal cancer using an in vitro clonogenic assay (HTCA). 294 30

A patient with metastatic colorectal carcinoma to the liver, who was being treated with a continuous systemic infusion of floxuridine (FUDR) through a permanent indwelling central venous catheter, developed bone pain. Bone imaging showed abnormal findings, without evidence of metastatic disease progression elsewhere. The patient's complaints and the abnormality seen on the bone scan resolved with removal of the catheter and discontinuation of the systemic infusion. Diagnostic and therapeutic considerations are discussed.
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PMID:A complication of prolonged infusional chemotherapy masquerading as a bone metastasis in a patient with colorectal carcinoma. 294 23


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