Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixty-eight unselected patients with progressive metastatic renal cell carcinoma (RCC) were treated between March 1985 and November 1988 with continuous infusion floxuridine (FUDR). Thirty-seven percent of these patients had previously received and failed systemic treatment. Using implantable pumps for automatic drug delivery, FUDR was continuously infused for 14 days at monthly intervals. The starting dose was 0.15 mg/kg/d (intravenous [IV]; n = 61) or 0.25 mg/kg/d (intraarterial [IA]; n = 7); IV doses were increased or decreased in increments of 0.025 mg/kg/d as permitted by toxicity. Diarrhea (with or without mild abdominal cramping) and nausea/vomiting limited the FUDR IV infusion, and hepatic function abnormalities limited FUDR IA infusion. The use of a circadian-modified infusion schedule permitted high FUDR doses to be safely given as compared with a constant rate infusion schedule. Of 63 patients assessable for response, 56 received systemic FUDR infusion. Four complete responses (CRs; 7.1%); and seven partial responses (PRs; 12.5%) were observed (objective response rate, CR plus PR, 19.6 +/- 5.1% [95% confidence limits] ). The median objective response duration was 10.8 months (range, 1 to 18 months; mean, 9.4 +/- 1.6). Four additional patients had minor tumor responses (MRs; 7.1%). In a subgroup of seven assessable patients receiving hepatic arterial FUDR, we observed one CR and three PRs (57.2 +/- 42.8%). Overall, objective response (CR plus PR) was seen in a quarter of assessable patients treated, 15 of 63, while only 15 of the 63 assessable patients (25.4%) have had objective tumor progression. The median follow-up time for all 68 patients was 28 months (range, 1 to 42), and their median survival duration is 15 months (range, 3 to 37 months). Continuous infusion FUDR is an effective outpatient treatment for progressive metastatic RCC, producing durable tumor response and causing little toxicity.
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PMID:Circadian-shaped infusions of floxuridine for progressive metastatic renal cell carcinoma. 214 18

During a 2-year period, cholangiography was performed on 17 patients with clinical evidence of cholestasis who were receiving hepatic intraarterial floxuridine (IA-FUDR) infusions for treatment of metastatic colorectal adenocarcinoma. The development of cholestasis was associated with persistently elevated alkaline phosphatase, but serial CT examinations of the liver showed no progression of the tumor. All patients had cholangiographic abnormalities (by endoscopic retrograde cholangiopancreatography, percutaneous transhepatic cholangiography, or operative cholangiography) of the biliary ductal system similar to those in idiopathic sclerosing cholangitis. Certain features, however, appear specific to IA-FUDR-induced cholestasis. All patients studied had segmental involvement at the common hepatic duct bifurcation. The cystic duct and gallbladder were often involved, but the distal common bile duct was spared. Histologic features of periportal and periductal fibrosis were present in specimens obtained from percutaneous liver biopsy in three patients, cholecystectomy in four patients, and autopsy in two patients. When clinical signs of hepatic dysfunction occur in the absence of tumor progression, biliary sclerosis must be suspected.
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PMID:Sclerosing cholangitis associated with hepatic arterial FUDR chemotherapy: radiographic-histologic correlation. 293 74

A prospective phase II evaluation of regional FUDR chemotherapy using a totally implantable drug infusion pump was conducted in 81 patients with colorectal metastases to the liver. The survival results were compared to a historical control group of 129 patients with isolated liver metastases. The two groups were comparable with respect to their dominant prognostic factors. The pump patients received their continuous chemotherapy on an outpatient basis and had an 88% response rate, as evidenced by a fall in their serum CEA levels by one-third or greater after two cycles of chemotherapy. By four criteria, the regional chemotherapy patients had an improved survival rate compared to the control series. First, the 1 year survival and median survival was better for the entire group of pump patients vs. controls (82% vs. 36%, 26 months vs. 8 months, p less than 0.0001). The survival for the regional chemotherapy patients was not influenced by the extent of tumor involvement, whether previous systemic 5-FU was given, or whether the patient had symptomatic disease. Second, the entire group of regional chemotherapy patients (including nonresponders) had a greater 1 year survival compared to the most favorable subgroup of control patients with the following characteristics: normal liver function tests, no symptoms, and only one lobe involved (82% vs. 66%, p = 0.009). Third, a subgroup of 49 pump patients, whose initial treatment for metastatic disease was regional chemotherapy (within 3 months of diagnosis) had a better 1 year survival than an exactly matched group of 49 control patients (67% vs. 30%, p = 0.000003). Fourth, the actuarial survival for all 81 pump patients was significantly better than predicted by a mathematical model constructed to predict the patient's clinical course based upon the seven dominant prognostic variables identified in a multifactorial analysis (82% survival at 1 year vs. 33% predicted survival). While liver metastases could be controlled in most patients, the major cause of death was tumor progression in extrahepatic sites, particularly lung metastases and abdominal carcinomatosis. Although it appears that regional chemotherapy with an implantable pump appears to prolong life by 12 to 18 months more than matched historical controls, these results must be confirmed by a randomized (phase III) prospective clinical trial.
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PMID:A prospective phase II clinical trial of continuous FUDR regional chemotherapy for colorectal metastases to the liver using a totally implantable drug infusion pump. 622 95

We used a murine tumor progression model for the evaluation of potential proliferation markers using positron emission tomography (PET). 5-[(18)F]-2'-deoxyuridine ([(18)F]FdUrd) was synthesized with >98% radiochemical purity and investigated in a pancreatic cancer model, transforming growth factor alpha transgenic mice crossbred to p53 deficient mice. Thymidylate synthase was increased already in premalignant lesions, whereas thymidine kinase 1 mRNA levels were up-regulated 4-fold in the pancreatic cancer specimen of these mice. PET imaging was performed after injection of 1 MBq of [(18)F]FdUrd and 1 MBq of [(18)F]fluoro-deoxyglucose. Animals with pancreatic cancer displayed focal uptake of both tracers. The [(18)F]FdUrd uptake ratio closely correlated with the proliferation index as evaluated in morphometric and fluorescence-activated cell sorter analysis. These results indicate the potential of our tumor model for the evaluation of PET tracers and suggest [(18)F]FdUrd as a tracer for the assessment of proliferation in vivo.
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PMID:In vivo evaluation of 5-[(18)F]fluoro-2'-deoxyuridine as tracer for positron emission tomography in a murine pancreatic cancer model. 1135 95