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-one patients with disseminated colon carcinoma and clinically significant liver metastases were treated with 5-FUDR via hepatic artery infusion (HAI). All patients had previously received systemic chemotherapy consisting of either 5-fluorouracil aone or in combination with other agents. At the time of the initiation of the HAI, clinical disease in all patients was progressing. A PR of hepatic metastases was noted in eight patients (35%) with a median and mean duration of response of 4.5 and 5.0 months respectively. The median and mean survival from the start of HAI for responders was 8.0 and 9.0 months and for nonresponders was 1.0 and 1.6 months respectively. It appears that a significant response rate can be achieved with HAI of 5-FUDR in spite of previous exposure to fluorinated pyrimidines.
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PMID:Hepatic artery infusion of 5-FUDR after prior systemic 5-fluorouracil. 13 80

The fact that the national death rate from carcinoma of the colon and rectum has remained static over the past two decades is strong incentive for future investigation of measures to allow detection in its early and more favorable stage. Although no significant improvements in surgical techniques have afforded improvement in longevity, certain technical factors are known to inhibit tumor implantation during surgery. Data suggest that the extent of en bloc resection is the most crucial factor in avoiding recurrence. Extensive use of radiotherapy as the sole method of treatment or as preoperative or postoperative adjunctive therapy remains investigational, but it seems likely that this form of treatment will play an increasing role in the future. Preoperative radiotherapy seems to be useful in reducing the stage of the neoplasm and the incidence of extraserosal involvement; postoperative radiotherapy is beneficial for palliation. Chemotherapy, particularly with the fluorinated pyrimidines (5-FU and 5-FUDR), is being evaluated for its usefulness in lengthening survival time; response to 5-FU is occasionally dramatic. It remains for major investigational centers to clarify the role of combination chemotherapy in metastatic disease. Immunotherapy at present must be considered an unproven mode of treatment and of inconclusive benefit in any stage of colorectal carcinoma. Carcinoembryonic antigen assay is a useful prognostic and diagnostic tool in localizing primary tumor and in subsequent evaluation of response to treatment.
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PMID:Colorectal carcinoma: overview of management techniques. 15 80

The results of a study based on intraaterial therapy applied to 65 cases of hepatic cancers (among which 42 cases of metastases of recto-colitic origin and 8 cases of primitive hepatomas) are reported. The catheters are insected percutaneously through the left brachial artery. After achort term treatment with Fluoro-Uracil FUDR is given continuously for over 20 weeks on the average, in ambulatory practice, using a Watkins chronofusor. A subjective response is reported in 88 p. 100 of the cases, an objective one in 74 p. 100. The mean survival time reckoning from the date of diagnosis is 16.6 months (it is somewhat longer in the cases of primitive hepatoma). The signs of systemic toxicity are frequent but mild; they seldom compel to discontinue the treatment. No death due to therapy has been register-d. The results are at least as good and even better with transcutaneous catheters than with catheters surgically inserted in the abdomen. They should encourage a wide spread of the method.
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PMID:[Fluorinated pyrimidines administered by percutaneous arterial perfusion in primary or secondary cancers of the liver]. 20 Feb 95

A rising CEA level is accepted as a sensitive indicator of recurrent colorectal carcinoma. In order to assess its efficacy in monitoring responses to chemotherapy in disseminated disease, 47 patients with documented metastatic colorectal cancer were studied. All had pretreatment CEA determinations and 40/47 (85%) patients had CEA levels greater than 4.0 ng/ml. Patients with hepatic metastases had the highest CEA values and none were found to have levels less than 4.0 ng/ml. Thirty patients received chemotherapy and had serial CEA determinations. 4/30 (13.3%) demonstrated probable tumor regression, 7/30 (23.3%) had stable disease, while 19/30 (63.3%) showed disease progression. CEA titers declined in all four responders, but in only one instance did the level fall to below 4.0 ng/ml and provide evidence of a tumor response not appreciated clinically. The only cytotoxic drugs effecting tumor regressions were 5-FU and 5-FUDR. CEA levels usually rose as disease progressed, but once elevated, absolute values did not correlate directly with tumor burden. The further usefulness of CEA assays in monitoring disseminated colorectal cancer awaits the development of improved chemotherapeutic agents.
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PMID:Carcinoembryonic antigen (CEA) as a monitor of chemotherapy in disseminated colorectal cancer. 70 11

Sixty-two patients with metastatic disease were treated with continuous infusion folinic acid (leucovorin calcium; Lv) and 2-deoxy-5-fluorouridine (floxuridine; FUDR). Lv was given by constant intravenous (IV) infusion at 500 mg/m2/d, days 1 to 6, while FUDR was given by IV push, days 2 to 6, at 3:00 PM daily with doses ranging from 294 to 1,214 mg/m2/d. This program was well tolerated with dose-limiting toxicities of diarrhea and stomatitis, while hematologic toxicity was minimal. Eighty-two percent of the assessable patients (46 of 56) had failed at least one chemotherapy regimen. One complete remission lasting 9 months and 10 partial remissions ranging from 5 to 10 months were observed in this heavily pretreated patient population for an overall response rate of 20%. These data suggest that the combination therapy with Lv and FUDR may have clinical use. Because of differing patient sensitivity to this drug combination, the recommended dose of FUDR for the initial therapy cycle is 500 mg/m2/d, days 2 to 6, with subsequent escalation to 900 mg/m2/d in those patients without extreme sensitivity. Phase II studies are now in progress with these doses.
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PMID:Phase I clinical trial with floxuridine and high-dose continuous infusion of leucovorin calcium. 182 39

T-506 is a novel synthetic FUDR derivative which releases FUDR slowly in vivo. We studied antitumor activity of T-506 by i.v. injection against mouse colon cancer, colon 26. When T-506 was administrated to mice daily, from day 1 through day 10, or every 3 days, on days 1, 4, 7, and 11, after s.c. inoculation of the tumor, the survival period was expanded significantly. The subcutaneous tumor growth was also inhibited according to the dose levels. Then, we compared the therapeutic effects on the experimental hepatic metastasis of colon 26 between T-506, 5'-DFUR and UFT at each maximal tolerable dose; that is, T-506 (0.074 m mole/kg/day; i.v. on days 1, 4, 7, and 10), 5'-DFUR (1.0 m mole/kg/day; P. O. from day 1 to 7), UFT (0.1 m mole/kg/day; P. O. from day 1 to 7). T-506 and 5'-DFUR suppressed completely the metastases of 5 of 6 (83.3%) mice and 6 of 7 (85.7%), respectively. UFT did not show a significant inhibitory effect. However, since the loss of body weight was more marked in T-506 than in the other two drugs, the side effect was thought to be a serious problem. These data suggested that if the side effect could be overcome, T-506 would be useful clinically for the treatment of gastrointestinal cancers or hepatic metastases.
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PMID:[Antitumor activity of T-506, a novel synthetic FUDR derivative, on murine colon cancer and its hepatic metastasis]. 182 81

To evaluate the use of angiotensin-II (A-II) as a means of improving results with intra-arterial infusions of hepatic tumors, 32 New Zealand white rabbits underwent perfusion of VX-2 hepatic implants. Tritium-labeled fluorodeoxyuridine [( 3H]FUDR) was administered via peripheral ear vein in 9 control rabbits (iv), via the hepatic artery in 12 rabbits (HA), and following a constant infusion of A-II in the remaining 11 rabbits (HA/A-II). Biopsies of tumor and normal hepatic parenchyma were taken and tissue levels of FUDR measured. Hepatic artery infusions, both with and without A-II, resulted in a significantly greater tumor uptake of FUDR than the iv infusions (P less than 0.001). More importantly, the tumor/liver ratio of FUDR uptake was significantly greater in the HA/A-II group (3.40) than that in the HA without A-II (0.98) group (P less than 0.001). This difference is due to the decreased FUDR uptake by normal hepatic parenchyma in rabbits undergoing A-II infusion; tumor drug uptake is similar for both groups. We conclude that the addition of angiotensin II to hepatic artery infusional chemotherapy significantly improves the tumor/liver ratio of drug uptake in this experimental model of hepatic metastases.
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PMID:Angiotensin alteration of drug uptake in an experimental model of hepatic metastases. 183 Sep 15

Direct hepatic arterial infusion of floxuridine (FUDR) (Roche Laboratories, Division of Hoffman-LaRoche Inc., Nutley, NJ, U.S.A.) has been used extensively in the treatment of metastases of colorectal tumors to the liver. The effectiveness of infusion and tolerance of the chemotherapy has been improved utilizing a totally implantable infusion pump delivery system. However, unequal distribution of drug infusion may occur to different parts of the liver parenchyma as demonstrated by hepatic arterial infusion scintigraphy (HAPS). We present a case of such unequal perfusion in which fatty metamorphosis of the liver occurred in the overperfused liver segment after FUDR therapy. The liver parenchymal changes were followed by serial computerized tomography scans and proven by biopsy during a minilaparotomy. Serial HAPS examinations show redirection of subsequent infusion to the opposite liver lobe due to parenchymal damage and vascular sclerosis. The importance of uniform liver perfusion and a rare dose-related effect of FUDR on liver parenchyma are thereby demonstrated.
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PMID:Fatty liver change as a result of hepatic artery infusion chemotherapy. 213 9

Based on laboratory studies showing enhanced cytotoxicity of floxuridine (FUDR) when used with high doses of leucovorin (LV), a pilot study of FUDR and LV through an implantable pump was initiated for the treatment of hepatic metastases from colorectal cancer. The highest dose of LV that could be administered, taking into account the constraints of the capacity of the pump and the solubility of LV, was 120 mg/m2/d. Due to the possibility of added toxicity, 25% of this dose was initially used. Twenty-four patients were treated at three dose levels. Eight patients were treated with the combination of LV (30 mg/m2/d) and FUDR (0.3 mg/kg/d) for a 14-day infusion through the pump, alternating with 2 weeks of saline. All eight patients had a greater than 50% decrease in measurable disease (PR) and a greater than 50% decrease in carcinoembryonic antigen (CEA) value; however, sclerosing cholangitis developed in two of these patients within 4 months. The next seven patients were treated with a lower dose of FUDR (0.2 mg/kg/d) and the same dose of LV, both for 14 days. Four of seven patients had a PR, and toxicity was decreased with no biliary sclerosis. A third regimen explored the combination of FUDR (0.3 mg/kg/d) and LV (30 mg/m2/d) for 7 days, alternating with 1 week of saline, to evaluate a shorter interval of treatment with the same overall dose intensity. Six of nine patients had a PR and all patients had a greater than 50% decrease in CEA value; sclerosing cholangitis developed in three of these patients. The overall response rate was 72%, with 18 of 25 patients alive after 1 year. The median survival time has not been determined, but it is greater than 27 months. FUDR with LV appeared to be effective in the treatment of hepatic metastases from colorectal carcinoma, but hepatic toxicity appeared to be greater than that previously reported with FUDR alone.
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PMID:Continuous intrahepatic infusion of floxuridine and leucovorin through an implantable pump for the treatment of hepatic metastases from colorectal carcinoma. 214 70

Primary and metastatic hepatic tumours--evaluation of tumour regression or response under regional cytostasis with sonography and fine needle puncture histology. The results obtained through the use of regional liver perfusion with a 5-FU-BCNU application on non-resectable hepatic metastases of colorectal tumours following primary curative removal of the primary tumour and primary hepatocellular carcinomas display comparable results to those specified in the literature after the use of 5-FUDR. The effectivity of the cytostasis regime is checked using histological criteria. The ultrasonically guided fine needle puncture can prove the success of the cytostasis regime on the basis of cytomorphologic criteria more reliably than has been the case up to now. Patients displaying histological signs of tumour regression have a significantly longer survival time than those displaying no signs of regression (12 +/- 9.2 vs 4.5 +/- 2.2 months; p less than 0.05).
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PMID:[Primary and metastatic liver tumors--evaluation of tumor regression and response with regional cytostatic drug therapy by sonography and fine needle puncture histology]. 216 47


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