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PubMedDate not supplied

Mitoxantrone, L-leucovorin and 5-fluorouracil: an effective and well tolerated first-line treatment for advanced breast cancer.

AIMS AND BACKGROUND: The combination of mitoxantrone plus leucovorin/fluorouracil in heavily pretreated patients with advanced breast cancer has shown significant activity and extremely good tolerability. The aim of this study was to evaluate the activity of this combination in patients not previously submitted to chemotherapy. METHODS: From May 1993 to December 1995 we treated 80 patients with advanced breast cancer with a combination of mitoxantrone, l-leucovorin and 5-fluorouracil. All patients had histologically or cytologically proven breast cancer, WHO performance status 0-3, normal hematological parameters and normal serum bilirubin. Prior chemotherapy for metastatic disease was not allowed, whereas adjuvant CMF (cyclophosphamide, methotrexate and 5-fluorouracil) or adjuvant anthracycline (doxorubicin or epirubicin) therapy was allowed; a single prior hormone treatment was permitted. Chemotherapy consisted of mitoxantrone 12 mg/m2 i.v. day 1, l-leucovorin 150 mg/m2 i.v. days 1, 2 and 3 and 5-fluorouracil 350 mg/m2 i.v. days 1, 2 and 3. The courses were repeated every 3 weeks. RESULTS: Objective response (CR + PR) was observed in 46/80 (57%) patients (95% CI, 46%-68%). Complete response (CR) was observed in 21/80 cases (26%). Response was observed in 14/24 (58%) patients with soft tissues as the dominant site of disease, in 22/34 (65%) patients with visceral involvement and in 10/22 (45%) of those with bone as the dominant site of disease. The median duration of response and survival was 9 months (range, 3-16) and 22 months (range, 2-48+), respectively. Toxicity was very manageable, with grade 4 leukopenia and thrombocytopenia in 6/80 (7.5%) and 1/80 (1.25%) patients, respectively, and negligible non-hematological toxicity. CONCLUSIONS: The combination of mitoxantrone, 5-fluorouracil and high-dose l-leucovorin is a safe and effective regimen for first-line treatment of advanced breast cancer.

Adult↗
PubMed2003

Phase II study of irinotecan and mitomycin C in 5-fluorouracil-pretreated patients with advanced colorectal and gastric cancer.

The aim of this phase II study was to investigate the tolerance and efficacy of a second-line irinotecan/mitomycin C combination in patients with advanced gastric or colorectal cancer, pretreated with 5-fluorouracil. Forty patients who had received 5-fluorouracil-based chemotherapy for advanced disease or adjuvant 5-fluorouracil treatment were enrolled. Chemotherapy consisted of irinotecan 125 mg/m2 and mitomycin C 5 mg/m2, given every 2 weeks. Treatment was continued until progression or limiting toxicity occurred. Five partial responses (12.5%), 22 cases of stable disease (55%) and 13 of progression (32.5%) were registered, giving an overall response rate of 12.5% [95% confidence interval (CI), 4.2-26.8%] and an overall control of tumor growth in 67.5% (95% CI, 50.8-81.4%) of patients. Median progression-free survival was 5 months, median survival time 8 months, and 1-year probability of survival was 21.6%. Diarrhea and neutropenia affected 25% and 12.5% of patients respectively, with only 7.5% experiencing grade 3-4 toxicity. There were no chemotherapy-related deaths or hospitalizations. This combination regimen was shown to be moderately effective with substantially lower toxicity than irinotecan monotherapy in 5-fluorouracil-pretreated patients with advanced gastric or colorectal cancer. It may represent an attractive option in patients at high risk for developing specific irinotecan toxicity.

Adenocarcinoma↗
PubMed2001

5-fluorouracil-induced cardiotoxicity mimicking myocardial infarction: a case report.

BACKGROUND: Severe cardiotoxicity is a documented, but very unusual side-effect of intravenous 5-fluorouracil therapy. The mechanism producing cardiotoxicity is poorly understood. CASE PRESENTATION: A case of 5-fluorouracil-induced cardiotoxicity, possibly due to coronary artery spasm, and mimicking acute anterolateral myocardial infarction is presented and discussed. Electrocardiographs highlighting the severity of the presentation are included in the report along with coronary angiograms demonstrating the absence of significant coronary atherosclerosis. CONCLUSION: Severe 5-fluorouracil-induced cardiotoxicity is rare, but can be severe and may mimic acute myocardial infarction, leading to diagnostic and therapeutic dilemmas. Readministration of 5-fluorouracil is not advised following an episode of cardiotoxicity.

Aged↗
PubMed2000

Phase II study of vinorelbine with protracted fluorouracil infusion as a second- or third-line approach for advanced breast cancer patients previously treated with anthracyclines.

PURPOSE: To evaluate the feasibility and activity of vinorelbine in association with protracted infusional fluorouracil in patients with advanced breast cancer who were previously treated with anthracycline-containing regimens. PATIENTS AND METHODS: Eighty-three consecutive patients were entered onto the study. Forty-three patients experienced treatment failure or relapse after anthracycline-based, first-line chemotherapy for advanced disease and 29 experienced treatment failure or relapse after first- and second-line approaches; 11 patients experienced progressive disease within 6 months of completion of adjuvant anthracycline therapy. Sites of involvement were as follows: liver involvement, 42 patients (50.6%); lung 24 (28.9%); bone, 49 (59.0%); and skin/lymph nodes, 21 (25.3%). Treatment consisted of vinorelbine 30 mg/m(2) administered on days 1 and 15 every 28 days and fluorouracil 200 mg/m(2)/d given continuously over a 24-hour period. RESULTS: Toxicity was recorded for 441 cycles. The scheme was well tolerated: grade 1/2 nausea/vomiting occurred in 13 patients (15.6%), grade 1/2 diarrhea in nine (10.8%), and grade 2/3 stomatitis in six (7.2%). Three patients (3.6%) experienced grade 3/4 leukopenia and four (4.8%) experienced grade 2/3 anemia. Grade 2/3 neurologic toxicity was observed in three cases (3.6%), and grade 2/3 hand-foot syndrome was observed in three (3.6%). The median relative dose-intensity was 92% and 100% for vinorelbine and fluorouracil, respectively. Six patients (7.2%) attained a complete clinical response and 45 (54.2%) attained a partial response, for an overall response rate of 61.4% (95% confidence interval, 50.9% to 71.9%). Twenty-one patients (25.3%) obtained disease stabilization, and 11 (13.3%) experienced disease progression. Median time to progression in responding patients was 15 months; median overall survival of the entire population was 22 months. CONCLUSION: Vinorelbine associated with protracted infusional fluorouracil is an active and manageable scheme in advanced breast cancer patients previously treated with anthracyclines. The response obtained is durable.

Adult↗
PubMed2001

Dose-intensive epirubicin-based chemotherapy is superior to an intensive intravenous cyclophosphamide, methotrexate, and fluorouracil regimen in metastatic breast cancer: a randomized multinational study.

PURPOSE: To determine the relative efficacy of a cyclophosphamide epirubicin and fluorouracil (CEF) regimen compared with an intravenous (IV) cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in metastatic breast cancer. PATIENTS AND METHODS: Patients were randomized to receive either CEF (cyclophosphamide 400 mg/m(2) IV, epirubicin 50 mg/m(2) IV, and fluorouracil 500 mg/m(2) IV on days 1 and 8), or CMF (cyclophosphamide 500 mg/m(2) IV, methotrexate 40 mg/m(2) IV, and fluorouracil 600 mg/m(2) IV on days 1 and 8). Treatment was given in 3- to 4-week cycles for a total of six to nine cycles. RESULTS: A total of 460 patients (223 CEF and 237 CMF) were randomized. Overall response rate was superior for CEF than CMF in all randomized patients (57% v 46%, respectively; P =.01) and in the assessable subset (66% v 52%, respectively; P =.005). With a median follow-up of more than 20 months, time to progression (TTP) was significantly longer with CEF than CMF (median 8.9 v 6.3 months, respectively; P =.0064), as was time to treatment failure (TTF) (median 6.2 v 5.0 months, respectively; P =.01). Significant survival differences were not observed between CEF and CMF (median 20.1 v 18.2 months, respectively; P =.23). Granulocytopenia and infections were similar in both arms. Grade 3/4 nausea/vomiting and alopecia were more frequent with CEF, whereas diarrhea was more frequent with CMF. Cardiac toxicity, primarily asymptomatic, required withdrawal from study of 15 patients on CEF (7%) and one patient on CMF. CONCLUSION: This CEF regimen safely provides significantly better tumor control than CMF, manifest as a higher response rate, and longer TTP and TTF, but not survival, when used as first-line chemotherapy for metastatic breast cancer.

Adult↗
PubMed2003

A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer.

PURPOSE: Three agents with differing mechanisms of action are available for treatment of advanced colorectal cancer: fluorouracil, irinotecan, and oxaliplatin. In this study, we compared the activity and toxicity of three different two-drug combinations in patients with metastatic colorectal cancer who had not been treated previously for advanced disease. PATIENTS AND METHODS: Patients were concurrently randomly assigned to receive irinotecan and bolus fluorouracil plus leucovorin (IFL, control combination), oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX), or irinotecan and oxaliplatin (IROX). The primary end point was time to progression, with secondary end points of response rate, survival time, and toxicity. RESULTS: A total of 795 patients were randomly assigned between May 1999 and April 2001. A median time to progression of 8.7 months, response rate of 45%, and median survival time of 19.5 months were observed for FOLFOX. These results were significantly superior to those observed for IFL for all end points (6.9 months, 31%, and 15.0 months, respectively) or for IROX (6.5 months, 35%, and 17.4 months, respectively) for time to progression and response. The FOLFOX regimen had significantly lower rates of severe nausea, vomiting, diarrhea, febrile neutropenia, and dehydration. Sensory neuropathy and neutropenia were more common with the regimens containing oxaliplatin. CONCLUSION: The FOLFOX regimen of oxaliplatin and infused fluorouracil plus leucovorin was active and comparatively safe. It should be considered as a standard therapy for patients with advanced colorectal cancer.

Adenocarcinoma↗
PubMed1981

Excretion of 1-hexylcarbamoyl-5-fluorouracil in urine of mice.

Excretion and metabolites in urine and feces of mice after oral administration of l-hexylcarbamoyl-5-fluorouracil-6-14C (14C-HCFU) or 5-fluorouracil-6-14C (14C-FU) were examined. After oral administration, about 90% of 14C-HCFU was excreted in urine within 48 h but not in feces. Major radioactive compounds in urine were 1-(3-carboxypropylcarbamoyl)-5-fluorouracil (CPRFU), FU, 5, 6-dihydro-5-fluorouracil (DHFU) and alpha-fluoro-beta-alanine (FBAL). Excretion ratio of these metabolites within 48 h was 13.5, 32.5, 20.2 and 23.9%, respectively, CPRFU and FU were rapidly excreted in urine after 14C-HCFU administration followed by DHFU and FBAL. Excretion of the latter two degradation products of FU was slower. On the other hand, major metabolites in urine after 14C-FU administration were DHFU and FBAL, but intact FU was slightly excreted. Excretion ratio of FU, DHFU and FBAL within 48 h was 4.8, 58.1 and 28.2%, respectively.

Animals↗
PubMed1996

Different intravenous administration techniques for 5-fluorouracil. Pharmacokinetics and pharmacodynamic effects.

The pharmacokinetics after 20 min intravenous infusion or a 2 min bolus (push) injection of 5-fluorouracil (500 mg/m2) were studied in 14 colorectal cancer patients. Treatment effects and toxicity related to the administration technique of 5-fluorouracil were retrospectively analysed in 198 colorectal cancer patients. The AUC after bolus injection was 6158 +/- 874 micromol/l*min compared to 3355 +/- 428 micromol/l*min after short-time infusion of 5-fluorouracil (p < 0.01). The mean peak-level after bolus injection was 341 +/- 34 microM versus 161 +/- 17 microM after a short-time infusion (p < 0.01). Patients receiving bolus injections had significantly better treatment result (32% partial remission) than patients receiving infusion (10% partial remissions, p < 0.001). Toxic side-effects were more frequently encountered after bolus injection but subjective improvement was also more frequently experienced by these patients. Bolus 5-fluorouracil push injection rather than a short-time infusion appears to be the more efficient administration technique.

Aged↗
PubMedDate not supplied

Potentiation by 2-deoxy-D-glucose tetraacetate of the antitumoral action of 5-fluorouracil in mice inoculated with L1210 ascites-producing cells.

Ascites-producing tumoral cells of the L1210 line were inoculated to syngenic mice. The gain in body weight and survival time were measured in untreated animals and mice injected intraperitoneally 1, 5 and 9 days after the administration of the tumoral cells with 5-fluorouracil (20-200 microg/g body wt.) and/or 2-deoxy-D-glucose tetraacetate (75 or 1,350 microg/g body wt.). The two agents failed to affect adversely the growth of control mice not inoculated with the tumoral cells. 5-fluorouracil caused a dose-related decrease in the body weight gain caused by the occurrence of the tumoral ascites and a dose-related prolongation of survival time. Although 2-deoxy-D-glucose tetraacetate, when tested in the low dose of 75 microg/g body weight opposed the effect of 5-fluorouracil on survival time, a higher dose of the ester (1,350 microg/g body weight) potentiated the effect of 5-fluorouracil to both decrease body weight gain and increase survival time. It is proposed, therefore, that 2-deoxy-D-glucose tetraacetate could be used to increase the cytostatic action of classical chemotherapeutic agents in the treatment of neoplastic diseases.

Animals↗
PubMedDate not supplied

Treatment of verruca plantaris with a combination of topical fluorouracil and salicylic acid.

A medical record review was conducted to determine the clinical outcome and average time to resolution of verruca plantaris in 20 patients treated with twice-daily applications of either 0.5% or 5.0% topical fluorouracil combined with topical 17% and 40% salicylic acid. Seven patients used 0.5% fluorouracil, and 13 used 5.0% fluorouracil. All of the lesions were sharply debrided at regular 1- or 2-week intervals. All 20 patients achieved full clinical resolution in a mean +/- SD of 82.5 +/- 56.6 days. Three patients (15%) had recurrent lesions, which subsequently resolved with repeated treatment. Two patients (10%) developed local dermatitis, which resolved with temporary discontinuation of the medication and the addition of a topical corticosteroid. It was observed that the twice-daily application of topical fluorouracil and salicylic acid is a safe and effective treatment for verruca plantaris.

Administration, Cutaneous↗
PubMed2006

Retinal toxicity of intravitreal 5-fluorouracil in silicone-filled rabbit eyes.

OBJECTIVE: To determine the retinal toxicity of 5-fluorouracil, by means of electroretinography and histopathology, at different doses in vitrectomized rabbit eyes injected with silicone oil. DESIGN: A pre-clinical experimental study. PLACE AND DURATION OF STUDY: The Louisiana State University Eye Center and the Department of Ophthalmology at the Tulane University Health Sciences Center, between June 1999 and May 2002. MATERIALS AND METHODS: Thirty-two New Zealand albino rabbits were used for the study. One eye per animal was used. After vitrectomy, the eyes were injected with 1 ml of silicone oil and then randomly divided into 4 groups. Group 1 was intravitreally injected with 0.2 ml of normal saline; Group 2 was injected with 200 microg of 5-fluorouracil; Group 3 was injected with 400 microg of 5-fluorouracil and Group 4 was injected with 800 microg of 5-fluorouracil. Electroretinography (ERG) was performed before and 14 days after intravitreal injections. Retinal histological examinations were performed after the animals were euthanized at the end of the experiment to document any retinal toxicity. RESULTS: There was less than 15 % ERG decrease in the eyes injected with normal saline and 200 microg of 5-FU. Moderate postoperative ERG decrease (30-50%) was seen in the animals injected with 400 microg of 5-FU. Eyes injected with 800 microg of 5-FU Silicone oil showed severe postoperative ERG decrease (80-100%). Histological examinations of the enucleated eyes were consistent with ERG results. No retinal toxicity was observed in the eyes injected with saline and 200 microg of 5-FU. Moderate retinal damage was seen in the eyes injected with 400 microg of 5-FU. Severe retinal damage was seen in the eyes injected with 800 microg of 5-FU. CONCLUSION: The results of this study suggest that doses lower than 2.5 mg of 5-FU are required for injection into silicone oil-filled vitrectomized rabbit eyes.

Animals↗
PubMed2000

Comparison of fluorouracil with additional levamisole, higher-dose folinic acid, or both, as adjuvant chemotherapy for colorectal cancer: a randomised trial. QUASAR Collaborative Group.

BACKGROUND: Standard adjuvant chemotherapy for colorectal cancer consists of fluorouracil with folinic acid or levamisole. The large QUASAR randomised trial aimed to investigate (in a two x two design) whether use of a higher dose of folinic acid or addition of levamisole to fluorouracil and folinic acid improved survival. METHODS: Patients with colorectal cancer, without evident residual disease, were randomly assigned fluorouracil (370 mg/m2) with high-dose (175 mg) or low-dose (25 mg) L-folinic acid and either active or placebo levamisole. The fluorouracil and folinic acid could be given either as six 5-day courses with 4 weeks between the start of the courses or as 30 once-weekly doses. Levamisole (50 mg) or placebo was given three times daily for 3 days repeated every 2 weeks for 12 courses. The primary endpoint was mortality from any cause. Analyses were by intention to treat. FINDINGS: Between 1994 and 1997, 4,927 patients were enrolled. 1,776 had recurrences and 1,576 died. Survival was similar with high-dose and low-dose folinic acid (70.1% vs 71.0% at 3 years; p=0-43), as were 3-year recurrence rates (36.0% vs 35.8%; p=0.94). Survival was worse with levamisole than with placebo (69.4% vs 71.5% at 3 years; p=0.06), and there were more recurrences with the active drug (37.0% vs 34.9% at 3 years; p=0.16). INTERPRETATION: The inclusion of levamisole in chemotherapy regimens for colorectal cancer does not delay recurrence or improve survival. Higher-dose folinic acid produced no extra benefit in these regimens over that from low-dose folinic acid. Trials of chemotherapy versus no chemotherapy will show whether these four treatments are equally effective or equally ineffective.

Adjuvants, Immunologic↗
PubMed2000

Semiphysiological model for the time course of leukocytes after varying schedules of 5-fluorouracil in rats.

Models of leukopenia after chemotherapy are mainly empirical. To increase the derived models' potential of mechanistic understanding and extrapolation, more physiologically based models are being developed. To date, presented models cannot characterize the often-observed rebound of leukocytes. Therefore, a model able to describe the transient decrease and rebound in leukocytes was developed. Three different dosing regimens of 5-fluorouracil were given to rats. One group received a single dose of 127 mg/kg. The other two groups received two and three injections of 63 mg/kg and 49 mg/kg, respectively, with a 2-day interval. Leukocyte counts were followed for 23 to 25 days after the first dose. Plasma concentrations were determined by high-performance liquid chromatography. Population pharmacokinetic and pharmacodynamic models were developed using NONMEM. 5-Fluorouracil showed one-compartment disposition with capacity-limited elimination. The 49-mg/kg dose injected on three occasions produced the lowest leukocyte count (28% of baseline) and the most prominent rebound of the schedules, despite the fact that the fractionated regimens produced only 52 to 56% of the area under the concentration-time curve from time 0 to infinity in the single-dose group. The final semiphysiological model included two 5-fluorouracil-sensitive and two -insensitive transit compartments as well as a compartment of circulating leukocytes. Second order rate constants from the transit compartments and a negative feedback from the circulating leukocytes to the input of the first sensitive compartment characterized the pronounced changes in leukocyte counts. A posterior predictive check as well as predictions into a new data set showed that our model could well predict the schedule-dependent leukopenic effects of 5-fluorouracil.

Animals↗
PubMed1975

Interaction of chemotherapeutic agents with methotrexate and 5-fluorouracil and its effect on de novo DNA synthesis.

The transport of methotrexate is known to be affected by corticosteroids and vincristine in L1210 leukemia cells. The deoxyuridine suppression test was used to measure the metabolic consequences of using these drugs with the antimetabolites, methotrexate and 5-fluorouracil, in both L1210 leukemia cells and normal human marrow cells. The deoxyuridine suppression test can be utilized as a sensitive measure of methotrexate and 5-fluorouracil biological activity in producing defective de novo DNA synthesis. The deoxyuridine suppression test was found to detect changes in biological activity equal to 20 ng (0.044 nmole) of methotrexate and 200 ng (1.94 nmoles) of 5-fluorouracil. Hydrocortisone and prednisone, but not dexamethasone or prednisolone, decreased the methotrexate effect to one-half in both L1210 and human cells as measured by the deoxyuridine suppression test. 5-Fluorouracil biological activity was not affected by any steroid studied. Vincristine produced variable results, but on the average it decreased the methotrexate effect in human marrow. Vincristine consistently decreased the methotrexate effect in L1210 systems. Cephalosporin, 75 mug/ml (0.214 mumole), had no effect. In parallel studies, hydrocortisone decreased the uptake of methotrexate, but no folic acid, in human and L1210 cells. The deoxyuridine suppression test warants further investigation as a method of screening drugs for interaction with antagonists of de novo DNA synthesis. This tudy extends earlier evidence of drug interaction with methotrexate in a murine system to human cells and demonstrates that there is a metabolic consequence, reduced potency of methotrexate, as a result of reduced transport produced by certain corticosteroids.

Animals↗
PubMedDate not supplied

Thymidine phosphorylase activity in transitional cell cancer: relation to histological parameters and chemosensitivity to fluorouracil-related drugs.

BACKGROUND: Thymidine phosphorylase (TdR-Pase) is an essential enzyme for the metabolism of fluorouracil-related drugs and it is also recognized as a potent angiogenic factor. We measured the TdR-Pase activity in human transitional cell cancers (TCCs) of the urinary tract to assess the relationship between TdR-Pase activity and degree of tumor malignancy. Furthermore, we investigated the relationship between TdR-Pase activity and chemosensitivity to fluorouracil-related drugs. MATERIALS AND METHODS: Sixty-two TCC tissues and 12 normal bladder tissues were obtained. TdR-Pase activity was measured with the enzyme-linked immunosorbent assay. The in vitro histoculture drug response assay was also performed to investigate tumor sensitivity to 5-fluorouracil (5-FU) and doxifluridine (5'-DFUR). RESULTS: The TdR-Pase activity of TCCs was three-fold higher than that of normal tissues. The TdR-Pase activity increased along with the histological grade, and the TdR-Pase activity of invasive cancers was significantly higher than that of superficial cancers. However, TdR-Pase showed no relationship with the sensitivity to 5-FU or 5'DFUR. CONCLUSION: A high TdR-Pase activity in human TCCs was confirmed to predict a high tumor grade and stage. However, the anti-tumor effect of fluorouracil-related drugs was independent of the TdR-Pase activity.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

Randomized trial of 5-fluorouracil, leucovorin and cisplatin in advanced pancreatic cancer.

BACKGROUND/AIMS: Phase II trials of combined 5 fluorouracil, leucovorin and cisplatin have demonstrated an 18-28% response rate in advanced pancreatic carcinomas. We investigated the effect of this chemotherapy regime on patients' survival. METHODOLOGY: Patients included gave informed consent. They had an advanced and proven pancreatic adenocarcinoma. The trial was multicentric, prospective and randomized. It compared a 5-day course of leucovorin (200 mg/m2/day), 5-fluorouracil (375 mg/m2/day) and cisplatin (15 mg/m2/day) repeated every 21 days (23 patients) with a control group (22 patients). The main end points were survival time (Kaplan-Meier and log-rank methods) a[not readable: see text]side effects of chemotherapy. RESULTS: Association of leucovorin, 5-fluorouracil and cisplatin failed to demonstrate any advantage of this regimen compared with supported care alone. Median survival times were 8.6 months (SD +/- 1.8) and 7.0 months (SD +/- 0.6), respectively. The modulation of 5-fluorouracil by leucovorin and cisplatin was well tolerated with moderate toxic effects. CONCLUSIONS: This multicentric trial failed to demonstrate any advantage of the evaluated chemotherapy regime in the palliative treatment of cancer of the exocrine pancreas. Other trials including gemcitabine and/or radiotherapy are needed in advanced pancreatic adenocarcinoma.

Adenocarcinoma↗
PubMed1999

[The combined therapy of carboplatin, fluorouracil and radiotherapy for moderate and advanced non-small cell lung cancer].

OBJECTIVE: To observe the effect of combined chemotherapy (carboplatin and fluorouracil) with radiotherapy for moderate and advanced non-small cell lung cancer. METHODS: Eighty patients with moderate and advanced non-small cell lung cancer were randomized into 2 groups, radiotherapy group(R) and carboplatin, fluorouracil plus radiotherapy group (CF + R). All patients in two groups received conventional radiotherapy. Patients in CF + R group received combined chemotherapy with carboplatin(100 mg, d 1-5) 5-fluorouracil(500 mg d 1-5) in the first and fourth weeks during radiotherapy. RESULTS: The complete response rate was 48% in CF + R group, 25% in R group. The 1-year, 3-year, 5-year survival rates were 63%, 38%, 18% in CF + R group, and 40%, 15%, 8% in R group. The major toxic reactions in CF + R group were grade I-II myelo-suppression and digestive tract reaction. CONCLUSIONS: Combined chemotherapy(carboplatin and fluorouracil) with radiotherapy is preferable for non-small cell lung cancer.

Aged↗
PubMed1998

[The uptake characteristics of 5-fluorouracil in the Caco-2 model system].

The uptake characteristics of 5-fluorouracil in the Caco-2 model system were studied. The uptake of 5-fluorouracil was determined at different pH and concentrations, and in the presence of various inhibitors. The results indicated that the uptake of 5-fluorouracil was the best at pH 6.0. The rate of uptake was saturable with a Km of 24 mmol.L-1, and a Vmax of 20.9 nmol.min-1.mg-1 protein. The uptake was inhibited by noncompetitive inhibitors such as NaCN, ouabain, and dipyridamole. The uptake was also inhibited competitively by analogous compounds such as uracil, thymine, and uridine (but not by hypoxanthine). In conclusion, the evidence suggests that 5-fluorouracil was transported by uracil carrier in Caco-2 cells.

Antimetabolites, Antineoplastic↗