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 559 records · Page 31Linked to original sources
PubMed2002

Schedule-selective biochemical modulation of 5-fluorouracil in advanced colorectal cancer--a phase II study.

BACKGROUND: 5-fluorouracil remains the standard therapy for patients with advanced/metastatic colorectal cancer. Pre-clinical studies have demonstrated the biological modulation of 5-fluorouracil by methotrexate and leucovorin. This phase II study was initiated to determine the activity and toxicity of sequential methotrexate--leucovorin and 5-fluorouracil chemotherapy in patients with advanced colorectal cancer. METHODS: Ninety-seven patients with metastatic colorectal cancer were enrolled onto the study. Methotrexate--30 mg/m2 was administered every 6 hours for 6 doses followed by a 2 hour infusion of LV--500 mg/m2. Midway through the leucovorin infusion, patients received 5-fluorouracil--600 mg/m2. This constituted a cycle of therapy and was repeated every 2 weeks until progression. RESULTS: The median age was 64 yrs (34-84) and the Eastern Cooperative Group Oncology performance score was 0 in 37%, 1 in 55% and 2 in 8% of patients. Partial and complete responses were seen in 31% of patients with a median duration of response of 6.4 months. The overall median survival was 13.0 months. The estimated 1-year survival was 53.7%. Grade III and IV toxic effects were modest and included mucositis, nausea and vomiting. CONCLUSIONS: This phase II study supports previously reported data demonstrating the modest clinical benefit of 5-FU modulation utilizing methotrexate and leucovorin in patients with metastatic colorectal cancer. Ongoing studies evaluating 5-fluorouracil modulation with more novel agents (Irinotecan and/or oxaliplatin) are in progress and may prove encouraging.

Abdominal Neoplasms↗
PubMed2004

Phase I/II study of first-line irinotecan combined with 5-fluorouracil and folinic acid Mayo Clinic schedule in patients with advanced colorectal cancer.

BACKGROUND: This multicentre phase I/II study was designed to determine the maximum tolerated dose of irinotecan when combined with 5-fluorouracil and folinic acid according to the Mayo Clinic schedule and to evaluate the activity of this combination as first-line therapy in patients with advanced colorectal cancer. METHODS: Sixty-three patients received irinotecan (250 or 300 mg/m2, 30- to 90-minute intravenous infusion on day 1), immediately followed by folinic acid (20 mg/m2/day) and 5-fluorouracil (425 mg/m2, 15-minute bolus infusion) days 1 to 5, every four weeks. RESULTS: Diarrhoea was dose limiting at 300 mg/m2 irinotecan in combination with 5-fluorouracil and folinic acid, and this was determined to be the maximum tolerated dose. Grade 3-4 neutropenia was the most frequently reported toxicity. The recommended dose of irinotecan for the phase II part of the study was 250 mg/m2. The response rate for the evaluable patient population was 36% (13/36), and 44% (16 patients) had stable disease (including 19% of minor response). For the intention-to-treat population, the response rate was 29% (14/49) and 35% (17 patients) stable disease (including 14% of minor response). The median time to progression was 7.0 months and the median survival was 12.0 months. Grade 3-4 non-haematological drug-related toxicities included delayed diarrhoea, stomatitis, fatigue, and nausea/vomiting. There were three deaths due to septic shock that were possibly or probably treatment-related. CONCLUSIONS: This regimen of irinotecan in combination with the Mayo Clinic schedule of bolus 5-fluorouracil/folinic acid every four weeks showed activity as first-line therapy in patients with advanced colorectal cancer. In keeping with other published results of studies using bolus 5-fluorouracil combined with irinotecan, the use of this regimen is limited by a relatively high rate of grade 3-4 neutropenia, and the combination of irinotecan and infusional 5-fluorouracil / folinic acid should remain the regimen of first choice.

Adenocarcinoma↗
PubMed2000

Sustained release of 5-fluorouracil from polymeric nanoparticles.

The use of biodegradable nanoparticles loaded with 5-fluorouracil was investigated as a potential means to sustain the release of this drug. Nanoparticles prepared from four biodegradable polymers were loaded with 5-fluorouracil using three loading concentrations of drug and three different concentrations of added polymer. Washing particles using a centrifugation/re-suspension with ultrasound protocol was found to dislodge the majority of drug, resulting in an over-estimation of incorporation efficiency and low levels of strongly entrapped drug. Increasing the initial 5-fluorouracil concentration before polymer/monomer addition increased the drug loading in both washed and unwashed particles. Increasing the amount of polymer used to make nanoparticles did not increase loadings, but did produce increased amounts of unusable polymer waste. Drug release from nanoparticles was evaluated using a Franz cell diffusion apparatus, which showed an initial burst effect followed by a slower release phase over 24 h. Indeed, nanoparticles prepared from poly(lactide-co-glycolide) released 66% of their 5-fluorouracil payload over this period. It was concluded that 5-fluorouracil-loaded nanoparticles could be readily included into a hydrogel-based delivery system to provide sustained drug release for trans-epithelial drug-delivery applications.

Delayed-Action Preparations↗
PubMed2005

Interindividual variability in 5-Fluorouracil metabolism and procainamide N-acetylation in human liver cytosol.

We investigated the enzymatic kinetics and interindividual variability of the metabolism of 5-fluorouracil and procainamide by human liver cytosol and/or microsomes. The Km values for the 5-fluorouracil dihydropyrimidine dehydrogenase (DPD) and procainamide N-acetyltransferase activities in pooled liver cytosol, and procainamide hydrolysis in pooled liver microsomes were 3.9, 1670, and 969 microM, respectively, and the intrinsic clearance (Vmax/Km) values for these reactions were 128, 0.192, and 0.0059 microl/min/mg protein, respectively. The cytosolic activities of 5-fluorouracil metabolism and procainamide N-acetylation ranged from 145 to 790 (469+/-156, mean+/-S.D., n=22) and <1 to 152 (52+/-48, n=12) pmol/min/mg protein, respectively, and the DPD activity of 5-fluorouracil was neither gender-related nor age-dependent. Procainamide N-acetylation activities among 12 human cytosol samples were highly correlated with sulfamethazine N-acetylation activities, suggesting that procainamide N-acetylation is catalyzed by N-acetyltransferase-2. These results suggest that the N-acetylation reaction is more important than the hydrolysis in the metabolic pathway of procainamide, and that there are large interindividual differences in the enzyme activities towards the respective metabolic pathways of 5-fluorouracil and procainamide in human liver.

Acetylation↗
PubMed1982

Antitumor activity of 1-acyloxymethyl derivatives of 5-fluorouracil against L1210 leukemia.

Antitumor activity of 15 1-acyloxymethyl derivatives of 5-fluorouracil was examined by both intraperitoneal injection and oral administration in L1210 leukemia system. Therapeutic ratio for dodecanoyloxymethyl derivative by intraperitoneal injection was 23 which was greater than that for 5-fluorouracil (11). On the other hand, undecanoyloxymethyl derivative of 5-fluorouracil showed the highest therapeutic ratio (5.8) when administered orally which was greater than that for 5-fluorouracil (1.9) and 1-(2-tetrahydrofuryl)-5-fluorouracil (1.0).

Administration, Oral↗
PubMed1985

The topical use of 5-fluorouracil in the ear in the management of cholesteatoma and excessive mucous secretion.

5-Fluorouracil was introduced in the early 1960s as a topical chemotherapeutic agent and has become increasingly accepted because of its efficacy, economy, and relative absence of side effects in treating many pre-cancerous conditions, certain benign and malignant tumors, and dermatoses. This paper addresses the use of topical 5-fluorouracil in the management of cholesteatoma and unwanted mucus-secreting cells. A retrospective study has suggested a very impressive efficacy of topical 5-fluorouracil in the management of cholesteatoma and, to a lesser degree, control of hyper-mucus-secreting cells at locations in the middle ear and mastoid. The use of topical 5-fluorouracil in the management of hyperkeratosis, cholesteatoma in the middle ear and mastoid, and in the external canal has been almost 100% effective with very few side effects. In the management of hyper-mucous-secreting cells, 5-fluorouracil has a success rate of approximately 50%.

Adolescent↗
PubMed2001

Activity and safety of vinorelbine combined with doxorubicin or fluorouracil as first-line therapy in advanced breast cancer: a stratified phase II study.

PURPOSE: To evaluate the efficacy and safety of vinorelbine combined with doxorubicin or continuous infusion of fluorouracil as initial therapy for advanced breast cancer. AUBJECTS AND METHODS: A total of 118 women who had not received chemotherapy for advanced breast cancer were enrolled and included in the intent-to-treat analysis. Subjects were stratified into two treatment groups. If subjects were candidates for anthracycline therapy, they received doxorubicin 50 mg/m(2) on day 1 and vinorelbine 25 mg/m(2) on days 1 and 8 (n = 62). If subjects had received adjuvant anthracycline therapy or had cardiac disease, they received fluorouracil 750 mg/m(2)/day by continuous infusion on days 1 through 5 and vinorelbine 30 mg/m(2) on days 1 and 5 (n = 56). The regimens were repeated every 21 days until evidence of progression of disease or severe toxicity. RESULTS: For doxorubicin and vinorelbine, the objective response rate was 55% (95% confidence interval [CI]: 42% to 68%), median time to disease progression was 34 weeks, median time to treatment failure was 32 weeks, and median survival was 92 weeks (95% CI: 72 to 128 weeks). For fluorouracil and vinorelbine, the objective response rate was 45% (95% CI: 31% to 59%), median time to disease progression was 32 weeks, median time to treatment failure was 30 weeks, and median survival was 53 weeks (95% CI: 47 to 64 weeks). The most common adverse event was grade 3 or 4 granulocytopenia, which occurred in 95% of subjects in the doxorubicin-vinorelbine group and in 88% of those in the fluorouracil-vinorelbine group. The most common nonhematologic adverse event was grade 3 or 4 stomatitis, which occurred in 9% and 32% of subjects in the two groups, respectively. CONCLUSION: Both vinorelbine-containing regimens appear to offer useful options as initial therapy for advanced breast cancer. Both regimens were active, and any efficacy differences between the two may have been related to differences in prognosis for the anthracycline-pretreated group (i.e., selection for prior aggressive adjuvant therapy) and or comorbid cardiac conditions. Both regimens were associated with predictable but manageable toxicity, but a lower dose of fluorouracil (e.g., 600 mg/m(2)/day) should be used to reduce the risk of stomatitis.

Adult↗
PubMed2006

Comparison of surface contamination with cyclophosphamide and fluorouracil using a closed-system drug transfer device versus standard preparation techniques.

PURPOSE: A comparison was conducted of the levels of surface contamination with two commonly used antineoplastic drugs, cyclophosphamide and fluorouracil, on countertops, floors, and hood surfaces in three oncology pharmacies following preparation with standard hazardous drug (HD) preparation techniques, or a closed-system drug transfer device (CSTD) in conjunction with standard HD preparation techniques, or a CSTD in conjunction with standard HD preparation techniques but prepared on a countertop outside the biological safety cabinet (BSC). METHODS: Wipe samples of the various surfaces in each pharmacy were obtained biweekly for 12 weeks (six samples) to establish a baseline. Following implementation of the CSTD, an additional six biweekly samples were collected. The CSTD was then removed, and a final six samples were collected again using standard preparation techniques. During the CSTD Phase, fluorouracil was prepared on the countertop outside the BSC. RESULTS: During the 36-week study, 342 samples were collected. A total of 8% positive fluorouracil wipe samples were found in the three pharmacies. The proportion of positive fluorouracil samples was significantly less in the CSTD Phase than in the control phases (p = 0.0002). There were 324 (95%) positive cyclophosphamide wipe samples. The median surface contamination was significantly different across the three phases (p < 0.00001). This was consistent at all sites, for both the BSC work surfaces and countertops. Contamination on floors adjacent to the BSCs was not consistently reduced. CONCLUSION: The use of a CSTD in the BSC in conjunction with standard HD preparation techniques significantly reduced cyclophosphamide surface contamination as compared to standard techniques alone. Preparation of fluorouracil outside the BSC using the CSTD did not result in significant analytically detectable contamination on the countertops.

Antineoplastic Agents↗
PubMedDate not supplied

Pharmacokinetics of 5-fluorouracil: inter-relationship with biochemical kinetics in monitoring therapy.

The major difficulty in using pharmacokinetic concepts for monitoring individual therapy with 5-fluorouracil is based on the mostly intracellular location of the active nucleotide metabolites of 5-fluorouracil with no clear correlation of plasma levels of the drug. In addition, the basic biochemical mechanism of 'thymine-less cell death' following inhibition of de novo thymidylate synthesis by 2'-deoxy-5-flurouridine 5'-monophosphate (FdUMP) is poorly understood, and only some of the biochemical determinants of therapeutic response to 5-fluorouracil are known. Individualised therapy with 5-fluorouracil requires an intergrated approach which should include methods of pharmacokinetics and biochemical kinetics. 5-Fluorouracil stands as an example for most of the pyrimidine and purine metabolites to which similar consideration apply in monitoring of cancer chemotherapy.

Animals↗
PubMed1999

Tegafur/uracil + calcium folinate in colorectal cancer: double modulation of fluorouracil.

The oral chemotherapeutic agent tegafur/uracil (UFT) is the first of a new class of anticancer drugs called dihydropyrimidine dehydrogenase inhibitory fluoropyrimidines. Tegafur/uracil combines uracil with the fluorouracil prodrug tegafur in a 4:1 molar ratio. Uracil competitively inhibits the degradation of fluorouracil, which results in the concentration of fluorouracil remaining at sustained levels in both plasma and tumour. Tegafur/uracil has been commercially available in Japan since 1983 and examined extensively in various tumours. Trials conducted in the US have focused on the combination of tegafur/uracil plus calcium folinate (calcium leucovorin) [ORZEL]. Several phase I and II trials have evaluated the maximum tolerated dose, pharmacokinetics, efficacy, and safety of this combination in the treatment of colorectal cancer. Results have shown that tegafur/uracil at 300 mg/m2/day in divided doses given every 8 hours for 28 days provides prolonged exposure to fluorouracil. Furthermore, tegafur/uracil + calcium folinate is well tolerated, with dose-limiting toxicity manifesting as diarrhoea. Compared with intravenous fluorouracil plus folinic acid (leucovorin) regimens, tegafur/uracil + calcium folinate has similar efficacy with less toxicity and is more convenient because it is an oral regimen. Early studies have also shown potential cost savings because of fewer complications.

Administration, Oral↗
PubMed1999

Improving fluorouracil chemotherapy with novel orally administered fluoropyrimidines.

During the 40 years since the initial synthesis of fluorouracil, there have been many attempts to improve fluoropyrimidine chemotherapy. These have included the utilisation of different schedules of fluorouracil administration, modulation of the metabolism of fluorouracil with other drugs to increase its therapeutic benefit, and the synthesis of prodrugs of fluorouracil that are potentially more effective and less toxic. Of particular interest at present is the clinical evaluation of several new fluoropyrimidine drugs that can be orally administered. These include capecitabine, tegafur/uracil (UFT), eniluracil (GW-776C85; 5-ethynyluracil), S-1, and emitefur (BOF-A2). The pharmacological principles that have influenced the development of these new drugs are initially presented. This is followed by a review of our current knowledge of the clinical pharmacology of each of these new agents, focusing on antitumour activity and toxicity from studies conducted in the US. Studies of capecitabine, tegafur/uracil, and early studies with eniluracil indicate that these drugs have at least similar activity to protracted fluorouracil infusion but with additional quality-of-life and economic benefits.

Animals↗
PubMed2000

From a classic approach in cancer chemotherapy towards differentiation therapy: acyclic and cyclic seven-membered 5-fluorouracil O,N-acetals.

Novel derivatives of 5-fluorouracil (5-FU) possessing a broader spectrum of antitumor activity and fewer toxic side effects than 5-FU have been sought. Herein, we report three different types of 5-FU O,N-acetals: a) a novel class of 5-fluorouracil-containing acyclonucleosides. The antitumor activities of such compounds were assessed against HEp human cells showing that (RS)-1-¿[3-(2-hydroxyethoxy)-1-cyclopentoxy]propyl¿-5-fluorouracil 3c is 4-fold more active than 5-FU. (RS)-1-¿[3-(2-hydroxyethoxy)-1-isopropoxy]propyl¿-5-fluorouracil 3b has important potential advantages over 5-FU because of its lower toxicity and its ability to induce myogenic differentiation in rhabdomyosarcoma cells. Our results suggest that this drug may be useful for differentiation therapy in this type of tumor; b) within the cyclic prodrugs of 5-FU, a series of new ring-expanded isosteres (1,4-oxaheteroepanes) of Ftorafur were synthesized. The level of diastereoselectivity in the preparation of cis and trans 1-(3-chloromethyl)-1,4-dioxepan-5-yl)-5-fluorouracil, although modest, suggests a potentially general approach for controlling the stereochemistry of this unexplored class of reactions involving the preparation of 5-FU seven-membered O,N-acetals; c) new 5-FU acyclic analogs containing two 5-FU moieties at both ends of the molecules with a linker having two amide bonds have been designed and synthesized. These bis(5-FU-O,N-acetals) show interesting antineoplastic activities against the HT-29 cell line.

Antineoplastic Agents↗
PubMed1987

Combination of 5-fluorouracil and cyclophosphamide in L1210 and P388 leukemias with changes in optimum treatments as a function of the age of the L1210 tumor at first treatment.

The interaction of 5-fluorouracil and cyclophosphamide in the treatment of L1210 and P388 leukemias was studied using response surface methodology. Single dose treatment of each drug was administered simultaneously or with a 24-hr interval between 5-fluorouracil and cyclophosphamide to the advanced tumors or at various times after L1210 inoculation. While at low doses the action of the combination of the two drugs was greater than expected, there was no therapeutic synergism if the drugs were given together (optimum doses cyclophosphamide 366 mg/kg and 364 mg/kg, respectively, in advanced L1210 and P388 leukemias) or in the early tumor when cyclophosphamide was given 24 hours after 5-fluorouracil. In the advanced tumor, using the regimen employing a 24-hr interval between drugs, therapeutic synergism could be demonstrated (optimum doses 5-fluorouracil 130 mg/kg followed by cyclophosphamide 248 mg/kg in advanced L1210 leukemia and 5-fluorouracil 110 mg/kg followed by cyclophosphamide 263 mg/kg in advanced P388 leukemia). The evidence generated suggested that improved therapy could be found in two separate regions of the treatment space, raising the possibility of more than one mechanism of drug interaction. The location of the optimal treatment depended on the tumor burden at the time treatment was initiated. A shift from one region to the other occurred after 4-6 days of tumor growth when the original inoculum was 10(5) i.p. L1210 cells. Another more obvious conclusion that can be drawn is that treatment was less effective as the tumor became more advanced. The notion that different tumor stages may require different ratios of drugs in a clinically useful combination should receive attention.

Animals↗
PubMed2003

Toxicities and therapeutic effect of 5-fluorouracil controlled release implant on tumor-bearing rats.

AIM: To investigate the toxicities, biodistribution and anticancer effect of 5-fluorouracil controlled release implant (5-FUCI) on Walker 256 carcinosarcoma cells in Wistar rats. METHODS: Experiment 1: Wistar rats were randomly divided into three groups (27 rats per group). Blank implant was implanted in left lobe of the liver, and rats were treated with saline solution (in group A) or 5-fluorouracil (subcutaneous injection, group B). 5-FUCI was inserted in left lobe of the liver (group C). The gastrointestinal and hematological toxicities were observed and contents of element F in group C were assayed. Experiment 2: on day 6 after Walker-256 carcinosarcoma transplantation in left lobe of the liver, 5-FUCI was implanted in right lobe of the liver (group E) or left lobe (group F), and rats in control group (group D) were inserted blank implant. Tumor inhibition rate and survival time were investigated. RESULTS: 5-FUCI showed no obvious toxic effect, extraction of Evan's blue from gastrointestinal tissue was normal, the peripheral white blood cells and bone marrow nucleated cells were not reduced, compared with control group (P>0.05). Histological examination revealed that there were no visible changes in small intestinal mucosa, The concentration of 5-fluorouracil in left lobe of the liver was 9.84, 28, 34 times as much as those of right lobe of the liver, heart and kidney respectively after the implantation in group C. They kept a high level of fluorouracil in left lobe of the liver, ranging from (4.414+/-0.482) % to (7.800+/-0.804) %, for eight weeks. Survival days were 28.0+/-2.2, 30.0+/-3.2 and 38.7+/-6.7 d in group D, E and F, respectively. CONCLUSION: 5-FUCI shows no obvious toxicities to gastrointestinal tract and myelotoxicity. After implantation, it kept a high level of 5- fluorouracil in surrounding tissues of the implant for eight weeks. Its antitumor effect on Walker-256 carcinosarcoma is demonstrated.

Animals↗
PubMed1986

Enhancement of 5-fluorouracil uptake into the bacterial cell by piperacillin.

The antibacterial activity of 5-fluorouracil, an antineoplastic agent, was found to be enhanced by piperacillin, a beta-lactam antibiotic, resulting in a synergism. It was considered that the synergism was caused by an increase of 5-fluorouracil uptake into the bacterial cell. On the other hand, amount of piperacillin bound to penicillin binding protein (PBP) did not change when 5-fluorouracil was added. The morphological change of the cell was due to the 5-fluorouracil when synergism appeared between 5-fluorouracil and piperacillin.

Bacteria↗
PubMed1999

A phase II study of weekly 24-h infusion of high-dose 5-fluorouracil in advanced pancreatic cancer.

No single agent or combination chemotherapy protocol, with the exception of gemcitabine, has so far proven superior to standard bolus 5-fluorouracil regimes for the treatment of advanced pancreatic cancer. The present phase II trial was designed to study whether the effectivity of 5-fluorouracil can be improved with a weekly high-dose 5-fluorouracil schedule. 26 patients with cytologically or histologically verified, metastasized (n = 21) or locally advanced (n = 5) previously untreated adenocarcinoma of the pancreas were included in this study. Treatment consisted of weekly applications of 2,600 mg/m2 5-fluorouracil as 24-h infusion on days 1, 8, 15, 22, 29, 36. Treatment was repeated at day 50 and was continued until disease progression. Primary endpoints of the study were response rates and toxicity, secondary endpoints were survival and clinical benefit in terms of performance status, body weight and analgesia consumption. Toxicity of the regimen was mild with only four instances of grade-3 toxicity. Response rates were 8% (95% CI = 1.2-13.7) with two partial remissions. Improvement of at least one parameter of clinical benefit for > or = four weeks was observed for 11.5% of the study patients. The most prominent effect was a transient stabilization of objective tumor measurements (48% [95% CI = 27.8-68.7]) and individual parameters of clinical benefit (50-75%). Median survival was 248 days (95% CI = 164-459) for all patients included in the study. The present study indicates that the high-dose 5-fluorouracil regimen shows weak activity in advanced pancreatic cancer which seems comparable to gemcitabine.

Adenocarcinoma↗
PubMed1975

Antitumor activity of carbamoyl derivatives of 5-fluorouracil by oral administration.

Antitumor activity of 1-carbamoyl derivatives of 5-fluorouracil was tested in L-1210 system by oral administration with two reference compounds, 5-fluorouracil and tetrahydrofuryl-5-fluorouracil (FT-207). The compounds tested were methyl-, ethyl-, isopropyl-, phenyl-, and cyclohexyl-carbamoyl-5-fluorouracil, and the therapeutic ratios (ILSmax/ILS30) of these compounds were 1.9, 2.2, 2.3, 1.0, and greater than 3.3, respectively, those of the two reference compounds being 1.7 and 1.0. Cyclohexylcarbamoyl-5-fluorouracil was the most effective of these compounds.

Administration, Oral↗
PubMedDate not supplied

Vinorelbine and 5-fluorouracil bolus and/or continuous venous infusion plus levofolinic acid as second-line chemotherapy for metastatic breast cancer: an analysis of results in clinical practice of the Gruppo Oncologico Italia Meridionale (GOIM).

BACKGROUND: This retrospective study evaluated the activity and toxicity profile of a regimen of vinorelbine and 5-fluorouracil with levofolinic acid, given to a large series of patients with recurrent or refractory metastatic breast cancer after first-line chemotherapy. PATIENTS AND METHODS: Overall, 286 evaluable patients were included in the analysis. Two chemotherapy schedules were reviewed: a) the bolus regimen consisted of levofolinic acid 100 mg/m2 and 5-fluorouracil 375 mg/m2, both administered i.v. on days 1,2 and 3, plus vinorelbine 25 mg/m2 i.v. bolus on days 1 and 8 every 3 weeks; b) the infusional regimen of levofolinic acid 100 mg/m2 given as a 2-hour infusion, followed by 5-fluorouracil 400 mg/m2 i.v. bolus and by 5-fluorouracil 600 mg/m2 administered as 22-hour continuous venous infusion (c.v.i) for 2 days, plus vinorelbine i.v. bolus on days 1 and 8. RESULTS: Overall, twelve patients achieved a complete response (4%; 95%CL 2%-7%) and 115 patients showed a partial response (40%, 95%CL 34%-46%), for an overall response rate of 44% (95CL 39%-50%). Sixty-one patients had stable disease (21%) and 98 patients progressive disease (34%). The tumor growth control rate was 63% (95%CL 60%-71%). Patients with soft tissue metastases as the dominant disease showed the highest response rate (56%), followed by viscera (48%) and bone (33%). The difference in response rate between patients with dominant visceral disease versus those with dominant bone disease was statistically significant (p=0.038). Patients treated with the bolus schedule achieved a 40% overall response rate with a 5% complete response rate, while those who received the infusional regimen had a 48% overall response rate with a 5% complete response rate. This difference was not statistically significant (p=0.164). The overall median duration of objective responses was 8.3 months (range 4-14 months), median time to progression of the all series was 6.1 months (range 2-24 months) and the median overall survival was 14.6 months (range 3-32). There was a statistically significant difference in survival among responder and non-responder patients (p=0.0009). CONCLUSION: The results of this large off-trial analysis confirmed the clinical activity and adverse-event profile reported in controlled clinical trials of the vinorelbine/ 5-fluorouracil with levofolinic acid regimen in clinical practice. This combination regimen was active with a low toxicity burden and, therefore, represents a good therapeutic choice for patients who require second-line chemotherapy.

Adult↗