Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

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

The amount of iododeoxyuridine (IdUrd) incorporated into DNA determines the degree of radiosensitization. Fluorodeoxyuridine (FdUrd) has been shown to biochemically modulate IdUrd incorporation into DNA in vitro and in vivo. In this Phase I study, these drugs were coadministered to patients during 14-day continuous i.v. infusion periods in order to investigate whether the incorporation of IdUrd into DNA in vivo could be increased without increasing the dose of IdUrd. IdUrd plasma concentrations and incorporation of IdUrd into DNA of granulocytes were measured by high-performance liquid chromatography. Up to 8.8% substitution of thymidine by IdUrd was observed. Even at 3.5 mg/m2/day FdUrd for 14 days (78% of the maximum-tolerated dose as a single agent), no clinically relevant enhancement of incorporation of IdUrd into DNA of granulocytes was observed. Also, no changes in plasma levels of IdUrd were observed with escalating doses of FdUrd. Toxicity patterns (stomatitis, diarrhea, and bone marrow depression) and isobologram analysis suggested that IdUrd and FdUrd had additive, rather than synergistic, effects.
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PMID:Fluorodeoxyuridine modulation of the incorporation of iododeoxyuridine into DNA of granulocytes: a phase I and clinical pharmacological study. 296 70

The response rate of metastatic colorectal carcinoma confined to the liver to HAI of FUDR alone is at the range of 50% and to mitomycin C by hepatic arterial infusion (HAI) at the range of 35%. Mitomycin C was added to FUDR by continuous infusion and given by HAI to 12 patients with colorectal cancer confined to the liver. Catheters were placed subselectively in the hepatic artery, and infusion continued for five to six days when the catheter was removed. Cycles were repeated every 30 days. Chemotherapy consisted of mitomycin C 15 mg/m2 administered on day 1 followed by FUDR 100 mg/m2 by continuous infusion daily for five days. Response to treatment was evaluated by serial determinations of plasma CEA and by imaging techniques consisting of a computerized tomography, sonography, and radionuclide scanning of liver as well as by angiography. In 2 patients, complete remission was achieved; in 4 patients a 75% and in another 4 patients a 50% decrease in liver metastasis was observed, while 2 patients had stable disease. Thus, a response rate of 83% with a median duration of six to seven months was achieved. The median survival of the these patients was 16 months. Eight of the 12 patients have failed previous, i.v. 5-FU containing regimens. Complications related to 45 treatment cycles were the following: catheter displacement in 11.1%, an intimal tear, usually in the hepatic artery in 4.4%, gastric ulcerations in 5.4%, and septicemia in 2.7% of the cycles. In addition, aneurysmal dilation of the hepatic artery occurred in 4 patients (8.8% of the treatment cycles), all of whom continued treatment. Chemotherapy-related complications included primarily thrombocytopenia and stomatitis. Mitomycin C + FUDR by hepatic arterial infusion is an effective treatment for colorectal carcinoma metastatic to the liver. The high response rate justifies the adjuvant treatment of Dukes class C colon cancer patients with this treatment.
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PMID:Percutaneous hepatic arterial infusion (HAI) of mitomycin C and floxuridine (FUDR): an effective treatment for metastatic colorectal carcinoma in the liver. 644 76

Natural history of patients with colorectal liver metastases is not significantly changed even by curative resection. The majority unfortunately relapse. The results of adjuvant treatment after resection were evaluated by analysis of 17 publications as well as by own data (60 patients). 340 patients were either treated by intraarterial (n = 201), systemic (n = 82), intraportal (n = 29) or intraperitoneal (n = 28) chemoinfusion (5-Fluorouracil or Floxuridine). An alternative approach was the treatment with specific immunotherapy using tumor vaccination (n = 35) or monoclonal antibodies (n = 20). Morbidity of adjuvant treatment includes local (chemical hepatitis, biliary sclerosis) and systemic (diarrhea, stomatitis) side effects. Technical complications could reach a level of up to 50% in case of local administration. With exception of 6 studies no comparison with a resection only group was performed. Despite postulated increase of survival and recurrence free time with historical controls the results of current ongoing studies are needed before general use of adjuvant treatment can be recommended.
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PMID:[Results of resection and adjuvant therapy of liver metastases of primary colorectal tumors--a review of the literature]. 750 91

Due to the pattern of tumor infiltration, hepatic resection may be accomplished in 20% of all patients with colorectal liver metastases. However, a new recurrence is observed very often and early. Up to date, systemic adjuvant treatment failed to improve the overall results. Taking into account the benefit of palliative intrahepatic chemotherapy, intraarterial therapy was performed as an adjuvant to removal of metastatic colorectal liver metastases in 51 out of 90 patients over an eight year period (1982-90). Due to abnormal arterial liver arteries 5 pat. got an intraportal catheter. The following monthly treatment schedules were applied: FUDR (fluorodesoxyuridine) 0.2-0.3 mg/kg/d/14 d (N = 12), FUDR 1,2 mg/kg/d/5d (N = 21), FUDR 1.0-1.7 mg/kg/d/5 and folinic acid 30 mg/m2/d (N = 18). Mortality (5.5%) and morbidity (36%) were not increased by catheter implantation. Local and systemic side effects were mainly stomatitis 0-22% and hepatobiliary toxicity 6-42%. Including an operative mortality of 5.5%, the median survival of 45 months was associated with a disease-free interval of 15 months. Intrahepatic recurrence was diagnosed after a median time of 26 months (extrahepatic recurrence was 25 months respectively). The following prognostic factors were associated with favourable survival: solitary metastasis (p > 0.001), curative resection, segmentectomy, normal serum levels of CA 19-9 and LDH. Although both groups were not comparable, due to more extended tumor infiltration in the treatment group (p = 0.03), adjuvant arterial chemotherapy delayed after curative resection intrahepatic recurrence to 52 versus 14 months (p = 0.036). Disease-free survival was improved to 19 versus 12 months (p = 0.08) resulting in a trend to better overall survival (p = 0.07).
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PMID:[Adjuvant regional chemotherapy after resection of liver metastases of primary colorectal tumors]. 832 38

Despite the increasing success of liver resection in treatment of metastatic colorectal cancer, at least 50% of patients will recur again in the remaining liver. In a non-randomized, prospective study we examined the benefit of regional adjuvant chemotherapy compared with surgical resection alone. Data from 81 consecutive patients who received curative liver resection and from 29 additional patients who underwent palliative liver resection were collected. Intraarterial adjuvant treatment with FUDR or 5-Fluorouracil was performed after liver resection in 60 patients. Mortality (5.5%) and morbidity (30%) were not increased by catheter implantation. Five or more cycles of intraarterial chemotherapy were completed in 39 (89%) of the curative resected patients. Depending on the treatment schedule the most frequent local and systemic side effects were stomatitis (13%) hepatobiliary toxicity and in two patients biliary sclerosis after a FUDR treatment of 14 days. In curative resected patients median time to intrahepatic recurrence was significantly delayed by adjuvant arterial treatment from 17 to 63 months (p = 0.015). Median survival time (overall 48 months) was increased from 33 months after surgery to 52 months (p = 0.064) and in case of 5 or more treatment cycles to 54 months (p = 0.046).
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PMID:The value of postoperative hepatic arterial infusion following curative liver resection. 942 88

High-dose chemotherapy combining regional hepatic artery infusion (HAI) of fluorodeoxyuridine (HAI FUDR) and systemic venous infusion of 5-fluorouracil (i.v. 5-FU) was delivered against liver metastases from colorectal cancer. The hypothesis that chronomodulation of delivery rate along the 24 h time scale would improve the tolerable doses of both drugs was tested. Combined HAI FUDR (80 mg/m2/day) and i.v. 5-FU (1200 mg/m2/day) were administered for five consecutive days every 3 weeks, either as a constant rate infusion (schedule A, 27 patients) or as chronotherapy (schedule B, 29 patients). This latter regimen consisted of a sinusoidal modulation of the delivery rate over the 24 h scale with a maximum at 16:00 for FUDR and 4:00 for 5-FU. Intrapatient dose escalation up to the individual maximum tolerated doses (MTD) was planned for both drugs in the absence of any previous grade 3 or 4 toxicity. All patients had metastatic colorectal cancer, with adjuvant or palliative chemotherapy given to six patients (22%) on schedule A and 12 patients on schedule B (41%). Severe stomatitis occurred in 71% of the patients and was dose limiting. No hepatic toxicity was encountered. Dose reductions of 5-FU and/or FUDR were required for 17 of 27 patients on schedule A (63%) as compared to 11 of 29 patients on schedule B (38%), following reaching the individual MTD (p<0.05). Over the first six cycles, patients on schedule B received higher doses (mg/m2/cycle; FUDR: 522 +/- 85 versus 499 +/- 50, p=0.004 and 5-FU: 5393 +/- 962 versus 5136 +/- 963, p=0.009) and higher dose intensities (mg/m2/week; FUDR: 164 +/- 46 versus 151 +/- 52, p=0.018 and 5-FU: 1652 +/- 478 versus 1553 +/- 535, p<0.041) of both drugs than patients on schedule A. As a result the number of courses with doses of 5-FU above 1200 mg/m2/day and/or FUDR above 110 mg/m2/day was larger in group B than in group A (5-FU, A: 67 of 268, 25% versus B: 133 of 321, 41% and FUDR, A: 86 of 268, 32% versus B: 155 of 321, 48%; p<0.001). Objective responses were observed in 13 patients on schedule A (48%) and 11 patients on schedule B (38%). The results support the need for further exploration of chronotherapy of colorectal cancer liver metastases with combined arterial and venous fluoropyrimidine chemotherapy.
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PMID:Continuous delivery of venous 5-fluorouracil and arterial 5-fluorodeoxyuridine for hepatic metastases from colorectal cancer: feasibility and tolerance in a randomized phase II trial comparing flat versus chronomodulated infusion. 1037 73