Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “FLUOROURACIL”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 901 records · Page 50Linked to original sources
PubMed2003

Phase I clinical study of infusional 5-fluorouracil with oxaliplatin and gemcitabine (FOG regimen) in patients with solid tumors.

BACKGROUND: The aim of this study was to determine the maximum tolerated dose, recommended phase II dose (RPTD) and toxicities of the FOG regimen (infusional 5-fluorouracil, oxaliplatin, gemcitabine). PATIENTS AND METHODS: Patients with advanced solid tumors were treated in an accelerated titration scheme. 5-Fluorouracil was administered intravenously at 200 mg/m(2)/day for 14 days and repeated every 21 days (one cycle). Gemcitabine was administered on days 1 and 8 over 30 min at 450-650 mg/m(2). Oxaliplatin was administered on day 1 over 2 h at 85-130 mg/m(2). For cycles 1, 3 and beyond, gemcitabine followed oxaliplatin; for cycle 2, gemcitabine preceded oxaliplatin. RESULTS: Forty-five and 39 patients were assessable for toxicity and response, respectively. Cycle 1 dose-limiting toxicities (DLT) included neutropenia, thrombocytopenia and diarrhea. No DLT was observed in cycle 1 at the first four dose levels (DL). At DL-5, two of four (50%) patients experienced DLT in cycle 1. Expanding DL-4, nine of 26 (35%) patients experienced DLT in cycle 1. Because recurrent grade 3 toxicities were observed in three of six (50%) patients at DL-3, DL-2 was considered the RPTD. At the RPTD, three patients had a partial response (response rate 23%). CONCLUSIONS: The RPTD for the 5-fluorouracil-oxaliplatin-gemcitabine combination is 200/100/450 mg/m(2). This novel regimen has demonstrated activity in advanced solid tumors and merits further investigation.

Adult↗
PubMed2005

Mucinous histology predicts for reduced fluorouracil responsiveness and survival in advanced colorectal cancer.

BACKGROUND: Mucinous carcinoma of the colon and rectum (mucinous CRC) is a histological subtype of colorectal adenocarcinoma for which there is little data on chemotherapy responsiveness. The purpose of this study was to investigate specifically the efficacy of fluorouracil-based first-line chemotherapy in patients with advanced mucinous CRC. PATIENTS AND METHODS: All patients with advanced mucinous CRC enrolled in three prospective randomized trials evaluating infused 5-fluorouracil as first-line treatment were compared with patients with non-mucinous subtypes enrolled in the same trials in a case-control study. Prognostic factors associated with overall response rate (ORR), progression-free survival (PFS) and overall survival (OS) were identified using univariate and multivariate logistic and/or Cox proportional hazards analyses. RESULTS: The study included 135 patients (45 cases and 90 controls). The response rates for cases and controls were 22% [95% confidence interval (CI), 11% to 38%] and 47% (95% CI, 36.1% to 58.2%), respectively (P=0.0058). Median OS for the mucinous CRC patients was 11.8 months (95% CI, 8.87-14.8) compared with 17.9 months (95% CI, 13.38-22.39) in the control group (univariate analysis, P=0.056); after correcting for significant prognostic factors by multivariate Cox regression analysis, P=0.0372 and hazard ratio (HR)=1.497 (1.02-2.19). CONCLUSION: Patients with advanced mucinous CRC have a poorer response to fluorouracil-based first-line chemotherapy and reduced survival compared with patients with non-mucinous CRC.

Adenocarcinoma, Mucinous↗
PubMed2006

A phase II study of high-dose bevacizumab in combination with irinotecan, 5-fluorouracil, leucovorin, as initial therapy for advanced colorectal cancer: results from the Eastern Cooperative Oncology Group study E2200.

AIM: Patients with untreated advanced colorectal cancer were enrolled to this single arm phase II multi-center cooperative group trial of bevacizumab combined with IFL. The first 20 patients received irinotecan (125 mg/m(2)), 5-fluorouracil (500 mg/m(2)) and leucovorin (20 mg/m(2)) weekly for four of six weeks and high-dose bevacizumab (10 mg/kg) every other week. Following a toxicity review of other trials using IFL, subsequent patients were enrolled at reduced doses of irinotecan (100 mg/m(2)) and 5-fluorouracil (400 mg/m(2)). RESULTS: Of the 92 patients accrued to the study, toxicity data are available for 87 patients and efficacy data for 81 patients. At a median follow-up of 37.5 months, median overall survival is 26.3 months, median progression free survival is 10.7 months and 1-year survival is 85%. The overall response rate is 49.4% (6.2% complete responses). A reduction in the starting doses of irinotecan and 5-fluorouracil decreased the occurrence of vomiting, diarrhea and neutropenia related complications. Bleeding occurred in 37 patients; all events but two were grade 1 or grade 2. There were nine reports of grade 3 or grade 4 thrombo-embolic events. Hypertension of any grade occurred in 13% of patients and proteinuria was infrequent. CONCLUSION: High-dose bevacizumab added to IFL is a well-tolerated and highly active regimen in patients with previously untreated metastatic colorectal cancer.

Adult↗
PubMed1998

Pharmacokinetics of cisplatin in combined cisplatin and 5-fluorouracil therapy: a comparative study of three different schedules of cisplatin administration.

BACKGROUND: Cisplatin is widely used in combination chemotherapy against a variety of tumors; however, the optimal administration schedule of cisplatin is still controversial. To clarify the pharmacokinetic differences according to the administration schedules of cisplatin, we compared three different administration schedules of cisplatin such as single short-term infusion, daily short-term infusion and daily continuous infusion in combination with 5-fluorouracil. Preliminary clinical responses and toxicities were also investigated. METHODS: A total of 12 courses in combination of cisplatin and 5-fluorouracil therapy was studied. The schedules of cisplatin tested were as follows: single short-term infusion (80 mg/m2, day 1,2 h div., n = 4), daily short-term infusion (20 mg/m2, days 1 to 5, 2 h div., n = 4), daily continuous infusion (100 mg/m2, 120 h, n = 4). In all schedules, 5-fluorouracil was continuously administered at a dose of 800 mg/m2/day on days 1 to 5. The area under the time-concentration curve (AUC) and the maximum concentration (Cmax) of total and free Pt were investigated. RESULTS: The highest AUC of total and free Pt and the lowest Cmax of free Pt were observed in the daily continuous infusion (total AUC; 162.53 +/- 18.39 micrograms h/ml, free AUC; 5.50 +/- 0.9 micrograms h/ml, free Cmax; 0.07 +/- 0.01 microgram/ml, mean +/- SEM). Two patients in the single short-term infusion and one patient in the daily continuous infusion indicated partial responses clinically. No nephrotoxicity or ototoxicity was observed. All toxicities were mild and tolerable in all regimens; however, the incidence of GI toxicity in daily continuous infusion seemed to be relatively higher. CONCLUSIONS: Daily continuous infusion of cisplatin gave the best pharmacokinetic results and to evaluate the clinical advantage of this schedule a prospective randomized trial should be conducted with sufficient numbers of patients.

Aged↗
PubMed1998

Toxic cardiogenic shock in a patient receiving weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin.

A 54-year-old man was treated with weekly 24-h infusion of high-dose 5-fluorouracil (2600 mg/m2) and leucovorin (100 mg/m2) for metastatic colon cancer. At first, he tolerated the treatment well and no significant toxicity was identified. After a total of eight courses of treatment, a stable disease was observed, but mild shortness of breath was found on occasion. The patient had no previous history of cardiac disease and the heart performance assessed by left ventricular ejection fraction before treatment was normal. Unfortunately, acute pulmonary edema with lethal cardiogenic shock occurred during the ninth course of treatment, in spite of intensive medical treatment. The chest X-ray showed extreme cardiomegaly. Repeated assessment of his heart function by echocardiogram and ventricular ejection fraction revealed a very poor cardiac performance. Toxic cardiogenic shock during weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin is extremely rare. To the best of our knowledge, no case has been reported in the English literature. We report a case and the relevant literature about the incidence, clinical picture and possible pathophysiology on 5-fluorouracil-related cardioxicity is reviewed.

Acute Disease↗
PubMed2005

Docetaxel + 5-fluorouracil + cisplatin 3-day combination chemotherapy as a first-line treatment in patients with unresectable gastric cancer.

BACKGROUND: Our objective was to verify the efficacy and safety of "docetaxel + 5-fluorouracil + cisplatin" 3-day combination chemotherapy as a first-line treatment in patients with unresectable gastric cancer. METHODS: Between January and November 2002, we enrolled 43 patients [males 31; median age 55 years (range 24-74)] with inoperable gastric cancer who had not been seen previously in Seoul National University Hospital. The regimen used was docetaxel 70 mg/m(2) on day 1, cisplatin 40 mg/m(2) on days 2 and 3, and 5-fluorouracil 1200 mg/m(2) over 10 h on days 1-3, every 3 weeks. RESULTS: A total of 168 cycles were administered. Mean cycle number per patient was 3.9. The administered dose intensity of docetaxel was 21.23 mg/m(2)/week, 5-FU 1092.14 mg/m(2)/week and cisplatin 23.82 mg/m(2)/week, which corresponded to 91.1, 91.0 and 89.5% of planned doses. Of the 43 patients, response evaluation was possible in 40 and, of these patients, 17 (42.5%) achieved a partial response, 13 (32.5%) stable disease, and 10 patients (25%) showed progressive disease. The median time to progression was 5.6 months [95% confidence interval (CI) 4.6-6.6 months]. Median overall survival was 9.0 months. (95% CI 4.8-13.2 months). Leukopenia occurred during 21.4% of cycles (36 of 168 cycles); 14.3% grade 1, 5.3% grade 2 and 1.8% grade 3. Anemia occurred in 16.7% (28 of 168 cycles); 11.3% grade 1, 4.8% grade 2 and 0.6% grade 3. Thrombocytopenia was not observed. Diarrhea, stomatitis and hypersensitivity occurred in 4.7% (two out of 43 patients), respectively. Neutropenic fever occurred in two patients (4.7%) and myalgia in three (7.0%). CONCLUSION: "Docetaxel + 5-fluorouracil + cisplatin" 3-day combination chemotherapy is an active and tolerable regimen as a first-line treatment in patients with unresectable gastric cancer.

Adult↗
PubMed1993

Comparison of adjuvant chemotherapy with methotrexate and fluorouracil with and without cyclophosphamide in breast cancer patients with one to three positive axillary lymph nodes.

BACKGROUND: Alkylating agents administered as single agents or in combination with antimetabolites or anthracyclines delay the appearance of metastases and prolong the survival of breast cancer patients after surgery. PURPOSE: This phase III clinical trial was designed to evaluate the therapeutic efficacy and toxicity of the alkylating agent cyclophosphamide in combination with the antimetabolites methotrexate and fluorouracil adjuvant to breast cancer surgery. METHODS: This study consisted of 255 breast cancer patients (a) with one to three histologically positive axillary lymph nodes and either no detectable primary tumor or operable primary tumors 5 cm or less (T0-T2) (95% of the patients) or (b) with tumors larger than 5 cm (T3) and with negative axillary nodes. Patients were randomly allocated to receive either methotrexate (60 mg/m2) and fluorouracil (600 mg/m2) (MF) intravenously on days 1 and 8 every 28 days for eight cycles or cyclophosphamide (100 mg/m2) orally on days 1-14 plus MF (CMF) every 28 days for the same duration. Median follow-up was 7.8 years, and maximum follow-up was 13 years. RESULTS: There were no statistically significant differences in time to treatment failure or overall survival for patients treated with MF or CMF. At 8 years after completion of treatment, time to treatment failure was 55% (95% confidence interval [CI] = 50%-60%) and 59% (95% CI = 54%-64%) and overall survival was 69% (95% CI = 65%-73%) and 67% (95% CI = 62%-72%) for MF- and CMF-treated patients, respectively. The hazard ratios (MF to CMF) for time to treatment failure and for survival, estimated with a proportional hazards model, were 1.02 (95% CI = 0.69-1.50) and 0.87 (95% CI = 0.56-1.34), respectively. Myelosuppression was significantly greater (P < .0001) in CMF-treated patients during cycles 1-6. Median white blood cell count nadirs were between 4.4 x 10(3)/microL and 3.5 x 10(3)/microL in patients receiving MF and between 3.0 x 10(3)/microL and 2.4 x 10(3)/microL in those receiving CMF. Dose reductions were more frequent in CMF-treated patients, which led to statistically significant differences (P < .0001) in amounts of methotrexate and fluorouracil administered. Primary cancers at other sites occurred in 14 patients (5.5%)--six treated with MF and eight treated with CMF. CONCLUSIONS: Our findings suggest that the addition of cyclophosphamide to adjuvant chemotherapy with MF offers no therapeutic advantage but results in increased myelosuppression. IMPLICATIONS: Future trials will define the possible advantages of antimetabolites in adjuvant therapy. Further information will also become available when results of the ongoing National Surgical Adjuvant Breast and Bowel Project trial comparing adjuvant MF to CMF in node-negative breast cancer patients are presented.

Adult↗
PubMed1991

Interactions of transfer RNA pseudouridine synthases with RNAs substituted with fluorouracil.

We have previously purified and characterized two different S. cerevisiae enzymes that produce pseudouridine specifically in nucleotide positions 13 and 55, respectively, in their tRNA substrates. The interactions of these enzymes with fluorinated tRNAs have now been studied. Such RNAs were produced by in vitro transcription using as templates synthetic genes that encode variants of a yeast glycine tRNA. RNAs substituted with fluorouracil were found to markedly inhibit pseudouridine synthase activity and the inhibitory effect of a tRNA was to a large extent dependent on the presence of fluorouracil in the nucleotide position where normally pseudouridylation occurs. Pseudouridine synthases were shown to form highly stable, non-covalent complexes with fluorinated tRNAs and we demonstrate that this interaction may be used to further characterize and purify these enzymes. The use of 5-fluorouracil as a cancer therapeutic agent is discussed in relation to our results.

Base Sequence↗
PubMed1990

Response and toxicity of cisplatin and 120-h 5-fluorouracil infusion in pretreated and untreated patients with advanced epidermoid cancer of the head and neck.

Eighty-two patients with advanced or recurrent squamous cell carcinoma of the head and neck were treated with bolus cisplatin and 120-h infusion of 5-fluorouracil. Among 49 pretreated patients, there were 9 complete and 12 partial responses, for an overall response rate of 43% and a median estimated survival of 8 months. Hematologic toxicity in this group was relevant, with 4 early deaths and 30% of cases with moderate to severe leukopenia; mucosal and renal toxicities were also important. Among 33 patients with no prior therapy, there were 8 complete and 17 partial responses, for an overall response rate of 76%. Fifteen of the 25 responding patients received subsequent locoregional treatment. The median estimated survival in this group was 29 months. Hematologic, mucosal, and renal toxicities were only mild to moderate. Episodes of possible 5-fluorouracil-related cardiotoxicity were recorded in both pretreated and untreated patients. Twelve of 41 partial responses observed after the second cycle of therapy were converted to complete responses with a third (8 cases) and also a fourth (4 cases) course. This study confirmed that cisplatin plus 5-fluorouracil is a first-choice combination in previously untreated patients. Definitive evidence that chemotherapy can favorable influence survival awaits confirmation by randomized trials, using a control arm with conventional locoregional treatment. In previously treated patients with recurrent disease, less intensive regimens not requiring hospitalization seem more useful for the quality of life.

Adult↗
PubMed1994

Allopurinol mouthwashes in the treatment of 5-fluorouracil-induced stomatitis.

This study was aimed at assessing the efficacy of allopurinol mouthwashes in the treatment of 5-fluorouracil-induced stomatitis. A randomized double-blind, placebo-controlled trial was thus designed to test its efficacy to treat oral mucositis in advanced cancer patients receiving 5-fluorouracil-containing chemotherapy. There were 44 patients randomized to receive allopurinol mouthwashes, or placebo, as soon as mucosal lesions were observed during any treatment cycle. Stomatitis was evaluated at the end of each 5-day treatment cycle. Allopurinol mouthwashes resolved stomatitis in 9 of 22 treated patients (40.9%), and diminished its intensity in 10 more patients (45.4%); stomatitis resolved completely in none of the 22 patients, and partially in 3 patients in the placebo group (p < .001 by chi 2 test). Duration of symptoms was also significantly different between the two groups (median: 4 days for the allopurinol group, 7.5 days for the control group; p < .0005 by Student's t-test). In conclusion, our results suggest that allopurinol mouthwashes can be effective to treat 5-fluorouracil-induced stomatitis.

Adult↗
PubMed1998

Dacarbazine, fluorouracil, and leucovorin in patients with advanced neuroendocrine tumors: a phase II trial.

Chemotherapy of neuroendocrine tumors must be improved. The most widely used regimen, which combines streptozotocin with fluorouracil, commonly obtains poor results. The best response rate that has been reported for carcinoid tumors is 33%. From July 1991 through September 1994, 18 patients who had advanced neuroendocrine tumors-including nine carcinoid tumors, seven neuroendocrine tumors of unknown primary site, one insulinoma, and one paraganglioma-were treated with a regimen of dacarbazine, 400 mg/m2/day, plus fluorouracil, 1 g/m2/day, with leucovorin, 200 mg/m2/day, for 2 days every 21 days (DTIC-LVFU2 protocol). The results were assessed according to the World Health Organization criteria of toxicity and response. Toxicity was moderate. The most severe side effects were grade 3 vomiting in two patients, grade 3 leukopenia in three patients, and grade 3 mucositis in one patient. The overall response rate was 27%, with only one partial response for carcinoid tumors but one complete and three partial responses for the other tumor types. Efficacy was insufficient in patients who had carcinoid tumors but the combination of dacarbazine with fluorouracil and leucovorin could be an effective regimen for the treatment of neuroendocrine tumors of unknown primary site.

Adult↗
PubMed1999

Phase II clinical trial of cisplatin, 5-fluorouracil, and ifosfamide as treatment for advanced locoregional head and neck carcinoma.

The association of ifosfamide with cisplatin and 5-fluorouracil for the management of advanced squamous cell carcinoma of the head and neck was assessed in this trial. Ifosfamide was given initially to 12 patients in combination with standard fixed doses of cisplatin and 5-fluorouracil, at 1,000 mg/m2 daily on days 2, 3, and 4. Two patients died of neutropenia and severe infection, and the authors recruited seven more patients who were treated with a lower dose of ifosfamide, 800 mg/m2 daily on days 2, 3, and 4. One of the seven patients died of neutropenia and severe infection. Three complete remission were observed in 18 patients evaluable for efficacy. The study was closed early because of the severe toxicity profile demonstrated by this scheme and because of no clear advantage in efficacy versus cisplatin plus 5-fluorouracil combinations.

Adult↗
PubMed2000

Combination chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in previously treated patients with advanced/recurrent head and neck cancer: a phase II feasibility study.

The purpose of this phase II feasibility trial was to determine the efficacy and toxicity of docetaxel combined with cisplatin and 5-fluorouracil in patients with locally advanced and/or recurrent squamous cell carcinoma of the head and neck. Nineteen patients entered the study. The majority had received prior radiotherapy but were chemotherapy naive. Treatment consisted of docetaxel 80 mg/m2 day 1, cisplatin 40 mg/m2 days 2 and 3, and 5-fluorouracil 1,000 mg/m2 by continuous infusion days 1 to 3. The cycle was repeated every 28 days. Most patients received granulocyte colony-stimulating factor, 150 microg/m2/day subcutaneously between days 4 and 8. The median number of chemotherapy cycles per patient was four. Dose reduction was done in three patients with no treatment delays. Of the 16 evaluable for response, seven patients (44%) demonstrated an objective response, including two complete and five partial ones; eight patients (50%) had stable disease; and one patient had progressive disease. The median time to progression was 7.5 months (range: 4-17.5 months). The median survival was 11 months (range: 1-18 months) and 1-year survival was 49%. Febrile neutropenia was recorded in 15% of courses. There were no toxic deaths. In conclusion, the combination of docetaxel, cisplatin, and 5-fluorouracil is an active regimen against previously treated squamous cell carcinoma of the head and neck with acceptable toxicity.

Adult↗
PubMed1987

5-Fluorouracil cardiotoxicity: left ventricular dysfunction and effect of coronary vasodilators.

Seven patients developed clinical features simulating myocardial ischemia less than 72 hours after 12 of 13 separate intravenous 5-fluorouracil administrations; 9 episodes were associated with chest pain, 3 with hypotension, 3 with ventricular tachycardia and 1 with cardiogenic shock. Left ventricular dysfunction was demonstrated by echocardiography in 5 separate episodes, 2 with interval improvement upon repeat echocardiograms. Pretreatment with nitrates and/or calcium channel blockers failed to prevent recurrence of cardiotoxicity during 5 of 6 repeat 5-fluorouracil administrations. Therapy with 5-fluorouracil is associated with cardiotoxicity simulating myocardial ischemia with left ventricular dysfunction. Pretreatment with coronary vasodilators may not prevent this phenomenon.

Aged↗
PubMed2000

Topical 5-fluorouracil as primary therapy for keratoacanthoma.

Keratoacanthoma is a common, benign cutaneous neoplasm that displays rapid growth on sun-exposed skin. Keratoacanthomas usually involute spontaneously after several months but rarely progress to squamous cell carcinoma. Because this is a benign, self-limited lesion of exposed skin, effective treatment should emphasize patient comfort and cosmetic results in addition to effectiveness. The authors present 2 patients with keratoacanthomas treated with topical 5-fluorouracil. Both patients had complete resolution of their lesions within 8 weeks. The cosmetic result was superb in both patients. Patient satisfaction with this therapy was excellent. Treatment can be instituted based on a clinical diagnosis; no diagnostic biopsy is necessary. Most keratoacanthomas respond to topical 5-fluorouracil therapy within 3 weeks, whereas squamous cell carcinomas respond poorly. Any lesion that shows a poor response after 3 weeks of therapy or that does not resolve within 8 weeks should undergo prompt excisional biopsy for definitive diagnosis and treatment. Topical 5-fluorouracil is an effective, convenient, relatively inexpensive treatment for keratoacanthoma that produces excellent cosmetic results. It should be added to the therapeutic armamentarium of all physicians who treat keratoacanthoma.

Administration, Topical↗
PubMed2000

Severe heart failure secondary to 5-fluorouracil and low-doses of folinic acid: usefulness of an intra-aortic balloon pump.

OBJECTIVES: To report 5-fluorouracil in combination with folinic acid as a cause of severe nonischemic heart failure and to demonstrate the potential usefulness of an intra-aortic balloon pump. DESIGN: Case report. SETTING: An adult, 19-bed medical/surgical intensive care unit of a university hospital. PATIENTS: A patient, who developed severe heart failure secondary to 5-fluorouracil infusion with low-dose folinic acid, which was introduced to treat a rectal cancer, was transferred from a cancer institute to our intensive care unit 4 days after the treatment was initiated. INTERVENTIONS: Electrocardiography, determination of level of cardiac enzymes, echocardiography, radial arterial catheterization, mechanical ventilatory support, continuous venovenous hemodialysis, vasopressors, and secondary intra-aortic balloon pump. MEASUREMENT AND MAIN RESULTS: During shock, the patient's systolic blood pressure progressively decreased to 70 mm Hg, despite inotropic agents and vasopressors. Transesophageal echocardiography showed a calculated left ventricular ejection fraction within 20% with global hypokinesia. Electrocardiography showed sinus tachycardia with only nonspecific ST-T changes. Results of serial determination of levels of cardiac enzymes were not significant for myocardial infarction. Treatment with an intraaortic balloon pump was initiated and resulted in a dramatical improvement within 48 hrs. The patient was gradually weaned from vasopressors and the intra-aortic balloon pump. By the tenth day, echocardiography showed a septoapical hypokinesia with a 50% left ventricular ejection fraction. On the 30th day, the echocardiography was considered normal. CONCLUSION: Intravenous 5-fluorouracil in combination with low doses of folinic acid can induce severe nonischemic heart failure. In such a case, an intra-aortic balloon pump could be useful by providing left ventricular function support when inotropic agents and vasopressors fail to restore normal hemodynamics.

Adenocarcinoma↗
PubMed2001

Combination cisplatin, 5-fluorouracil and radiation therapy for locally advanced unresectable or medically unfit bladder cancer cases: a Southwest Oncology Group Study.

PURPOSE: Patients with locally advanced bladder cancer or who are not medically fit for surgery are a therapeutic dilemma. Radiotherapy with or without single agent cisplatin has been the major therapeutic modality. A phase II Southwest Oncology Group trial investigated the efficacy and feasibility of 5-fluorouracil, cisplatin and radiation in this patient subset. MATERIALS AND METHODS: Eligible patients had muscle invasive bladder cancer (clinical stages T2-T4) with nodal involvement at or below the level of bifurcation of the iliac vessels, were medically or surgically inoperable, or refused cystectomy. Patients underwent pretreatment cystoscopy and detailed tumor mapping, and were treated with 75 mg. /m.2 cisplatin on day 1 and 1 gm./m.2 daily, 5-fluorouracil on days 1 to 4 and definitive radiotherapy. Chemotherapy was repeated every 28 days, twice during and twice after radiation. RESULTS: From October 1993 to April 1998, 60 patients were enrolled in study. Of the 56 eligible patients 34% had unresectable tumors, 21% were not medically fit for surgery and 45% refused cystectomy. Overall, 68% of the patients had clinical T3 tumors or greater and 22% had nodal metastasis. Treatment was completed as planned in 32 of 56 (57%) patients. The most frequent grade 3 or 4 toxicities were neutropenia, stomatitis or mucositis, diarrhea, neuropathy and nausea. There were 53 patients who were evaluable for response, although response was not determined for 18. The overall response rate was 51% (95% confidence interval [CI] 37 to 65) based on intent to treat with a complete response rate of 49% (95% CI 35 to 63). Estimated median survival of the 56 patients was 27 months (95% CI 21 to 40 months) with an overall 5-year survival of 32%. The 5-year survival of the 25 patients who refused surgery was 45%. CONCLUSIONS: Concurrent 5-fluorouracil, cisplatin and radiation therapy is feasible. Despite a promising complete response rate, the overall 5-year survival suggests the need for more effective systemic therapy. The 5-year survival of patients who refused cystectomy suggests that this combined modality may provide another alternative to cystectomy for these patients.

Aged↗
PubMed1999

Decrease in adhesion formation by a single application of 5-fluorouracil after flexor tendon injury.

Using an animal model, the effect of a single intraoperative application of 5-fluorouracil on digital flexor tendon adhesions was assessed. After a standard partial division of the tendon and immobilization with a stitch, the synovial sheath in 30 rabbit tendons was treated with 5-fluorouracil solution (50 mg/ml)-soaked sponge pledgets for 5 minutes. Buffered saline was substituted for 5-fluorouracil in 30 control tendons. The tendons were harvested 1 week postoperatively, and histologic sections were assessed with a light microscope. There was a significant reduction in synovial sheath thickening (p < 0.001), cell counts (p < 0.001) and proportional length of adhesions (p < 0.001) in the treated tendons. The reduction in synovial reaction and adhesion formation using this "one touch" technique presents a novel strategy for the management of the clinical problem of postoperative adhesions complicating tendon injury and repair.

Animals↗