Leucovorin In Patients Research Articles

Oxaliplatin/5-FU chemotherapy without leucovorin in metastatic colorectal cancer

3734 Background: Oxaliplatin, 5-FU and leucovorin combination chemotherapy is one of effective regimen for metastatic colorectal cancer, even in patients who received 5-FU previously. But, in this regimen, the role of ( high dose) leucovorin in patients who previously received 5-FU and leucovorin is unknown. And the response rate of oxaliplatin/5-FU without leuconvorin given as the first regimen is almost similar to that of with leucovorin. We evaluated the effect of oxaliplatin and 5-FU without leucovorin in patients with metastatic colorectal cancer. Methods: Twenty four patients with metastatic colon(n=15), rectal (n=9) cancer were enrolled in this study. There were 9 male and 15 female patients and their median age was 63(range 37–74). Seventeen patients were received 5-FU and leucovorin previously. All patients received oxaliplatin 85mg/m2 on day 1 and, 5-FU bolus infusion 400mg/m2 on day 1 and continous infusion 600mg/m2/22hrs on days 1 and 2. The chemotherapy was repeated every 3 weeks. Response rate and toxicity were evaluated according to WHO criteria and NCI toxicity criteria respectively. Results: The median cycles of chemotherapy was 6(range1–9). Three were not evaluable. There were 6 partial responses with 25% response rate. In previously treated and untreated patients, the response rate were 23.5% (4/17) and 28.5%(2/7) respectively. The median survival time was 18 months(range 4–32). There was no grade III or IV toxicity except one grade 3 anemia. Conclusions: Oxaliplatin/5-FU combination chemotherapy without leucovorin showed good response and very tolerable toxicity. No significant financial relationships to disclose.

Oxaliplatin/5-FU chemotherapy without leucovorin in metastatic colorectal cancer

3734 Background: Oxaliplatin, 5-FU and leucovorin combination chemotherapy is one of effective regimen for metastatic colorectal cancer, even in patients who received 5-FU previously. But, in this regimen, the role of ( high dose) leucovorin in patients who previously received 5-FU and leucovorin is unknown. And the response rate of oxaliplatin/5-FU without leuconvorin given as the first regimen is almost similar to that of with leucovorin. We evaluated the effect of oxaliplatin and 5-FU without leucovorin in patients with metastatic colorectal cancer. Methods: Twenty four patients with metastatic colon(n=15), rectal (n=9) cancer were enrolled in this study. There were 9 male and 15 female patients and their median age was 63(range 37–74). Seventeen patients were received 5-FU and leucovorin previously. All patients received oxaliplatin 85mg/m2 on day 1 and, 5-FU bolus infusion 400mg/m2 on day 1 and continous infusion 600mg/m2/22hrs on days 1 and 2. The chemotherapy was repeated every 3 weeks. Response rate and toxicity were evaluated according to WHO criteria and NCI toxicity criteria respectively. Results: The median cycles of chemotherapy was 6(range1–9). Three were not evaluable. There were 6 partial responses with 25% response rate. In previously treated and untreated patients, the response rate were 23.5% (4/17) and 28.5%(2/7) respectively. The median survival time was 18 months(range 4–32). There was no grade III or IV toxicity except one grade 3 anemia. Conclusions: Oxaliplatin/5-FU combination chemotherapy without leucovorin showed good response and very tolerable toxicity. No significant financial relationships to disclose.

Phase I and pharmacokinetic study of 24-hour infusion 5-fluorouracil and leucovorin in patients with organ dysfunction

Patients with hepatic or renal dysfunction are often treated with 5-fluorouracil (5-FU), but there are few data to confirm the safety of this practice. Patients with solid tumors were eligible if they were able to fit into one of three organ dysfunction cohorts: I, creatinine >1.5 but < or =3.0 mg/dl and normal bilirubin; II, bilirubin >1.5 but <5.0 mg/dl with normal creatinine; or III, bilirubin > or =5.0 mg/dl with normal creatinine. 5-FU doses were escalated separately within each of the three cohorts. Leucovorin (LV) dosage was fixed at 500 mg/m(2). 5-FU was given as a 24-h infusion at 1000, 1800 or 2600 mg/m(2), and plasma concentrations were measured every 3 h during the first two infusions for each patient. Sixty-four patients were treated. Toxicities did not appear to be related to organ dysfunction cohort. A weekly dose of of 5-FU 2600 mg/m(2) produced dose-limiting toxicity (DLT) in six of 20 evaluable patients. These DLTs included grade 3 fatigue (n = 3), grade 2 neutropenia precluding weekly dosing (n = 1), grade 3 thrombocytopenia (n = 1) and grade 3 mental status changes (n = 1). There was no relationship between serum bilirubin or serum creatinine and 5-FU clearance. Patients with elevated bilirubin may be safely started on a weekly regimen of 5-FU 2600 mg/m(2) with leucovorin 500 mg/m(2) as a 24-h continuous infusion.

Uracil/tegafur plus oral leucovorin does not affect survival rates but may be better tolerated than standard fluorouracil and leucovorin for previously untreated metastatic colorectal cancer: Abstracted from: Douillard J, Hoff P, Skillings J et al. Multicenter phase III study of uracil/tegafur and oral leucovorin versus fluorouracil and leucovorin in patients with previously untreated metastatic colorectal cancer. Journal of Clinical Oncology

About one in 20 people in the United States and Europe will suffer from colorectal cancer in their lifetime. Half of these develop distant metastases. Standard treatments for metastatic colorectal cancer are based on intravenous fluorouracil combined with leucovorin. Newer oral treatments such as uracil/tegafur are now available.

Pirarubicin, UFT, Leucovorin Chemotherapy in Non-embolizable and Transcatheter Arterial Chemoembolization-Failed Hepatocellular Carcinoma Patients; A Phase II Clinical Study.

Hepatocellular carcinomas are one of the most common malignancies in the world. However, no effective therapeutic modality has been proven to prolong the survival of patients in an inoperable stage. The purpose of this study was to determine the response rate and the toxicities of a combination of pirarubicin, UFT and leucovorin in patients with non-embolizable hepatocellular carcinomas, or who had progressed during their transcatheter arterial chemoembolization treatment. Of 23 patients with a hepatocellular carcinoma, 11 had progressed during a transcatheter arterial chemoembolization, with the other 12 being transcatheter arterial chemoembolization-naive. All the patients were treated with pirarubicin (70 mg/m2 i.v., day 1), UFT (350 mg/m2 P.O., day 1~21), and leucovorin (25 mg/m2 P.O., day 1~21). Twenty patients were able to be evaluated, with a partial response being achieved in four, giving an overall response rate of 20% (95% confidence interval, 7~44%). The median overall survival time was 6 months, and the median survival time of the transcatheter arterial chemoembolization-naive patients was significantly longer than that of those treated by transcatheter arterial chemoembolization (p=0.012). The most significant dose-limiting toxicity was leucopenia and thrombocytopenia. The combination of pirarubicin, UFT and leucovorin therapies showed marginal antitumor activity and significant toxicity in patients with non-embolizable or failed transcatheter arterial chemoembolization hepatocellular carcinomas.

Novel arterial infusion chemotherapy using cisplatin, 5-fluorouracil, and leucovorin for patients with advanced hepatocellular carcinoma

Advanced hepatocelluar carcinoma (HCC) has a poor prognosis. In this study, the authors evaluated the efficacy of chemotherapy using cisplatin (CDDP), 5-fluorouracil (5-FU), and leucovorin (LV), comparing our regimen with chemotherapy using CDDP and 5-FU. Nineteen patients with advanced HCC were treated by arterial infusion of a chemotherapeutic agent via a subcutaneously implanted injection port. In Group A ( n=9), one course of chemotherapy consisted of the daily administration of CDDP (10 mg/1 h, on 5 days) and LV (12 mg/10 min, on 5 days) followed by 5-FU (250 mg/5 h, on 5 days). In Group B ( n=10), except for the administration of LV, the same regimen was employed. This course was repeated each week for 4 weeks. In Group A, two patients showed a complete response (CR), and the other three showed a partial response (PR). In Group B, two patients showed PR. The response rate (CR+PR/all cases) in Group A was significantly higher than that in Group B (56 vs. 20%; P=0.022). The 1- and 2-year survival rates of Group A (66.7, 44.4%) were significantly higher than those of Group B (10, 0%) ( P=0.033). These results suggest that our regimen may be useful in treating patients with advanced HCC.

Phase II Study of Gemcitabine, UFT and Leucovorin in Patients with Advanced Pancreatic Cancer

The combination of gemcitabine with protracted 5-fluorouracil(5-FU) in the treatment of metastatic pancreatic cancer has shown activity with tolerable toxicity. The administration of UFT may simulate the effects of a protracted infusion of 5-FU. Patients with previously untreated metastatic or unresectable measurable pancreatic adenocarcinoma received gemcitabine (800 mg/m2 i.v., administered as an 80-min infusion on days 1, 8 and 15), UFT (200 mg/m2/day, on days 1 to 21), and oral leucovorin (90 mg/day, on days 1 to 21). Thirty patients were enrolled in this study. Five patients had partial responses, with an overall response rate of 17% (5/30), using the intent-to-treat principle (95% confidence interval (CI), 3-30%). Nine out of 25 (36%) patients experienced clinical benefit responses (95% CI; 17-55%). The median time to progression was 3.0 months, and the median overall survival was 7.2 months. The principal adverse event was neutropenia. The combination of gemcitabine, UFT, plus oral leucovorin shows significant antitumor activity and a beneficial clinical effect with an acceptable level of toxicity.

Weekly High-dose 5-Fluorouracil (5-FU), Leucovorin (LV) and Bimonthly Cisplatin in Patients with Advanced Gastric Cancer

A phase II clinical trial was performed to evaluate the activity and toxicity of bimonthly cisplatin and weekly 24-h infusion of high-dose 5-fluorouracil and leucovorin in patients with advanced gastric cancer. From September 1997 to March 1998, 23 chemo-naive patients of advanced gastric cancer were enrolled in this study. The regimen consisted of weekly 24-h infusion of 5-FU (2,600 mg/m2) and LV 150 mg and bimonthly cisplatin (25-50 mg/m2) bolus for 12 weeks followed by a 2-week break. There were 10 male and 13 female patients with a median age of 52 years. A total of 428 chemotherapy treatments were given with a mean of 11. Seventeen patients were evaluable for response. There were 41% (7/17) partial response, 18% (3/17) stable disease and 41% (7/17) progressive disease. The grade III or IV toxicity included anorexia 35% (8/23), fatigue 26% (6/23), vomiting 17% (4/23) and mucositis 9% (2/23). One patient developed perforated duodenal stump after chemotherapy. One patient died of hyperammonemia-related coma. The median times to disease progression and overall survival were 3.5 and 7 months, respectively. This regimen showed modest activity against gastric cancer. However, there was no survival advantage and there was greater toxicity than with weekly high-dose 5-FU-LV alone.

A phase II study of irinotecan with 5-fluorouracil and leucovorin in patients with previously untreated gastric adenocarcinoma

A phase II study testing the safety and efficacy of irinotecan (CPT-11). 5-fluorouracil (5-FU), and leucovorin (LCV) was conducted in patients with advanced gastric adenocarcinomas. Patients with metastatic or recurrent adenocarcinoma of the gastroesophageal junction (GEJ) or stomach were entered onto this study. Previous chemotherapy for metastatic disease was not allowed. Treatment consisted of repeated 6-week cycles comprising CPT-11 125 mg/m2 intravenously (i.v.) followed immediately by LCV 20 mg/m2 i.v. and 5-FU 500 mg/m2 i.v., all given weekly for four weeks followed by a two-week rest. Thirty-eight patients were enrolled and 36 eligible patients received protocol therapy. Grade 3-5 toxicities consisted primarily of neutropenia (36%) and diarrhea (28%). Neutropenic infection was observed in 14% of patients, with 3 (8%) dying of neutropenic sepsis. The overall response rate was 22% (95% confidence interval [CI] 8.5% to 35.5%). Median survival was 7.6 months, and median time to progression was 4.4 months. This weekly regimen of CPT-11 with bolus 5-FU/LCV is active in patients with advanced adenocarcinomas of the stomach or gastroesophageal junction. While rates of grade 3-4 neutropenia and diarrhea were similar to those observed historically in patients receiving this regimen for colorectal cancer, neutropenic fever/sepsis appeared to be more frequent, and dose modifications were substantial. Future trials of this combination in patients with gastric cancer should decrease the absolute starting drug doses and/ or employ altered scheduling that better accommodates the pattern of toxicity.

Treatment of non-resectable pancreatic cancer with intraperitoneal 5-FU and leucovorin IV

Aim: To explore the feasibility of intraperitoneal (IP) 5-fluorouracil (5-FU) and (IV) leucovorin for patients with advanced pancreatic carcinoma. Materials and Method: Thirty patients (11 men), median age 65 (range 36–74 years), with a non-resectable pancreatic carcinoma in stage III (n=2) and IV (n=28) were treated with IP 5-FU 750–1000 mg/m2and leucovorin IV 100 mg/m2for 2 days every 3rd week. Tumour effect was analysed with repeated computed tomography (CT) scans, performance status was estimated with Karnofsky's index (KI) and morphine consumption, and toxicity assessed using World Health Organization (WHO) criteria. Results: Median survival time was 7 months (range 0–21). There was no difference in survival between patients with different grading, staging or tumour size. Regional and systemic toxicity: The treatment was well tolerated, with no grade III or IV complications or side-effects. The median KI showed a minor reduction during treatment. The median morphine consumption per 24 hours increased from 0 mg (range 0–250) at inclusion, to 70 mg (range 0–540) at exclusion. The median nadir (WBC) was 7.2×103/mm3(range 5.2–18.8). All patients had abdominal discomfort and distension during IP installation. Conclusion: Intraperitoneal administration of 5-FU is feasible for patients with nonresectable pancreatic carcinoma. The treatment can induce a temporary stabilization of tumour growth and eventually prolong survival without adverse effects.

Phase II trial of epirubicin, cisplatin, oral uracil and tegafur, and leucovorin in patients with advanced gastric carcinoma

Phase II trial of epirubicin, cisplatin, oral uracil and tegafur, and leucovorin in patients with advanced gastric carcinoma

Phase II Study of Gemcitabine, 5-Fluorouracil, and Leucovorin in Patients With Pancreatic Cancer

The primary goal of this phase II study was to determine the efficacy of gemcitabine (Gemzar; Eli Lilly and Company, Indianapolis, IN) plus 5-fluorouracil in patients with pancreatic cancer. Eligibility criteria included nonresectable locally advanced or metastatic pancreatic adenocarcinoma and measurable disease. Gemcitabine at 1,000 mg/m(2) and leucovorin at 20 mg/m(2) were administered intravenously 30 minutes before 5-fluorouracil 600 mg/m(2), weekly for 3 of every 4 weeks. Twenty nine patients were enrolled. The overall response rate was 21% (95% confidence interval: 8% to 40%), consisting of one complete response and five partial responses; 16 patients (55%) had stable disease. Median survival was 8.4 months (95% confidence interval: 2.6 to 14.2), and actuarial 1-year survival was 36%. Neutropenia (grade 3 only) was reported in 3.4% of patients, but was generally of short duration. No thrombocytopenia or evidence of cumulative myelosuppression was observed. The only significant nonhematologic events were grade 3 diarrhea and alopecia (both 3.4%). Gemcitabine plus 5-fluorouracil is active and well tolerated compared with results reported for each of these single agents. Thus, this combination justifies future comparative clinical trials. Semin Oncol 28 (suppl 10):44-49.

Pharmacokinetics of escalating doses of CCI-779 in combination with 5-fluorouracil and leucovorin in patients with advanced solid tumors

Pharmacokinetics of escalating doses of CCI-779 in combination with 5-fluorouracil and leucovorin in patients with advanced solid tumors

A phase I study of escalating doses of CCI-779 in combination with 5-fluorouracil and leucovorin in patients with advanced solid tumors

A phase I study of escalating doses of CCI-779 in combination with 5-fluorouracil and leucovorin in patients with advanced solid tumors

A phase I trial of PKC412, an inhibitor of protein kinase C, in combination with bolus 5-Fluorouracil and leucovorin in patients with stage IV colorectal cancer

A phase I trial of PKC412, an inhibitor of protein kinase C, in combination with bolus 5-Fluorouracil and leucovorin in patients with stage IV colorectal cancer

Bioavailability and phase II study of oral UFT plus leucovorin in patients with relapsed or refractory colorectal cancer

Bioavailability and phase II study of oral UFT plus leucovorin in patients with relapsed or refractory colorectal cancer

A systematic overview of chemotherapy effects in colorectal cancer.

A systematic review of chemotherapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for the evaluation of the scientific literature are described separately (Acta Oncol 2001; 40: 155-65). This synthesis of the literature on adjuvant and palliative therapy with cytostatics for colorectal cancer is based on 208 scientific articles, including eight meta-analyses and 162 randomised studies. These studies involve approximately 126,800 patients. The conclusions reached can be summarized into the following points: The benefit of postoperative adjuvant chemotherapy with fluorouracil and levamisole in patients with colon cancer stage Dukes' C was demonstrated more than ten years ago in two phase III trials. There was a reduction of recurrence from 56% to 39% and reduction of death from 51% to 40% after more than five years of follow-up. Although this combination has been widely accepted as standard adjuvant treatments for stage Dukes' C colon cancer, there is still debate on whether adjuvant treatment with fluorouracil alone would be equally efficacious. Several phase III trials with postoperative adjuvant chemotherapy with fluorouracil and leucovorin in patients with colon cancer stage Dukes' C have demonstrated a similar statistically significant improvement in disease-free and overall survival in comparison with a control arm. Six months of treatment with fluorouracil and leucovorin is as efficient as twelve months of fluorouracil and levamisole. This treatment is, thus, recommended for routine use. No convincing benefit from adjuvant chemotherapy is proven in colon cancer stage Dukes' B although some randomised trials have shown the same relative survival gain as seen in stage Dukes' C. There is less knowledge on survival benefits from adjuvant chemotherapy for Dukes' stage B and C rectal cancer. In small randomised trials, postoperative radiochemotherapy has, however, improved survival to the same extent as chemotherapy in colon cancer Dukes' stage C. A meta-analysis of nine randomised trials revealed a small but statistically significant benefit in five-year survival and a reduction in the risk of death for the patients receiving immediate postoperative portal vein infusion compared with controls. At present, however, the use of portal vein infusion or intraperitoneal therapy outside of a research trial cannot be recommended in the light of the limited effects. This conclusion is further supported by similarly limited effects in two recently reported very large European multicentre trials. In advanced colorectal cancer, chemotherapy may prolong survival, decrease tumour-related symptoms, improve general well-being or maintain it at a high level for a longer time period compared with best supportive care. These effects have been seen using systemic chemotherapy and using regional chemotherapy in patients with metastases limited to the liver. Subjective responses and quality of life improvements are seen more frequently than objective tumour remissions. Although the impact on overall survival is modest, i.e. an improvement in median survival of five to six months, treatment is recommended also outside clinical trials. High-dose infusional regimens with modulated fluorouracil may turn out to be superior to conventional bolus regimens, since they result in more tumour regressions, longer times to disease progression and possibly longer survival. A plateau seems, however, to have been reached with fluorouracil, giving objective response rates of up to 30% to 40% with a variety of modulators. Randomised studies of regional therapy, mostly hepatic arterial infusions, of liver metastases in colorectal patients have demonstrated significantly higher response rates than systemic fluorouracil therapy alone without impact on overall survival. The importance of the higher response rates for patient benefit in the predominantly asymptomatic patients with isolated liver metastasis remains to be elucidated. Regional therapy in advanced disease cannot be recommended outside of clinical trials. New cytotoxic agents are emerging with antitumour activity similar to fluorouracil-based chemotherapy. The addition of oxaliplatin or irinotecan to existing fluorouracil regimens improves response rates and duration of response, and possibly overall survival. Based upon the results of two randomised studies, there is a role for irinotecan as second line therapy for selected patients who have failed first-line therapy with fluorouracil plus leucovorin. The role of these agents, alone or in combinations, in clinical routine remains, however, to be determined due to more pronounced toxicity than caused b

Isolated hepatic perfusion for unresectable hepatic metastases from colorectal cancer

Background. Unresectable colorectal liver metastases are a significant clinical problem. Isolated hepatic perfusion (IHP) is a regional treatment technique that delivers high dose chemotherapy, biologic agents, and hyperthermia via a completely isolated vascular recirculating perfusion circuit as a means of regionally treating liver tumors. This study presents our results of IHP with tumor necrosis factor (TNF) plus melphalan or IHP with melphalan alone followed by infusional floxuridine (FUDR) and leucovorin in patients with advanced or refractory unresectable hepatic colorectal metastases. Methods. Fifty-one patients with unresectable colorectal hepatic metastases underwent a 60-minute IHP with 1.5 mg/kg melphalan and hyperthermia (39°C to 40°C). Thirty-two patients received IHP with 1 mg TNF with melphalan and 19 patients had IHP with melphalan alone followed by monthly hepatic intra-arterial infusional (HAI) FUDR (0.2 mg/kg/day) and leucovorin (15 mg/M2/day) for 14 days monthly for up to 12 months. Twenty-six patients failed 1 or more previous treatment regimens for established hepatic metastases and 27 had greater than 25% hepatic replacement (PHR) by tumor. Patients were monitored for response, toxicity, and survival. Results. There was 1 perioperative death (2%), and only 2 patients (4%) had measurable perfusate leak during IHP (both less than 4%). In the 32 patients treated with IHP alone there were no detectable systemic TNF or melphalan levels during perfusion. The overall objective radiographic response rate (all partial [PR]) was 76% (38 of 50 assessable patients) with a median duration of 10.5 months (range, 2 to 21 months). Twenty-four of 31 patients (77%) had a PR after IHP alone and 14 of 19 (74%) after IHP with postperfusion HAI. Median duration of response was 8.5 months after IHP alone and 14.5 months after IHP and HAI; median survival was 16 and 27 months, respectively. There were 18 PRs in 26 patients (69%) whose prior therapy had failed and 18 PRs in 27 patients (67%) with PHR of 25 or greater. Conclusions. IHP can be performed with acceptably low morbidity and has significant antitumor activity in patients with unresectable hepatic metastases from colorectal cancer including those with refractory disease or PHR of 25 or greater. HAI appears to prolong the duration of response after IHP, and this combined treatment strategy deserves additional clinical evaluation as a therapeutic modality in this setting. (Surgery 2001;129:176-87.)

Phase II study of oral eniluracil, 5-fluorouracil, and leucovorin in patients with advanced colorectal carcinoma

The oral administration of 5-fluorouracil (5-FU) is hindered by erratic bioavailability due to catabolism of 5-FU by the enzyme dihydropyrimidine dehydrogenase (DPD) in the gastrointestinal tract. Eniluracil is a potent inactivator of DPD which results in 100% oral bioavailability of 5-FU. Leucovorin (LV) is another biochemical modulator of 5-FU that potentiates inhibition of thymidylate synthase, the primary target of 5-FU. The goal of this study was to determine the antitumor activity and toxicity of an oral regimen containing eniluracil, 5-FU, and LV in patients with colorectal carcinoma. Sixty eligible patients who had previously untreated, measurable, metastatic colorectal carcinoma were treated with oral eniluracil 50 mg on Days 1-7, 5-FU 20 mg/m(2) on Days 2-6, and LV 50 mg on Days 2-6. Cycles were repeated at 28-day intervals. The overall response rate was 13% (95% confidence interval [CI] = 6, 25%), with 1 complete response and 7 partial responses. Three additional patients had partial responses that were not confirmed at subsequent evaluations. The median time to progression of disease was 4.4 months (95% CI = 3.45, 7.69) and the median survival time was 12.6 months (95% CI = 9.1, 14.75). Grade 3-5 toxicity (1 toxic death) occurred in 51 patients (85%). Grade 4 neutropenia occurred in 25 patients (42%), and 18 patients (30%) had Grade 3-4 diarrhea. Twenty-one patients (35%) were hospitalized for toxicity, and 12 (20%) had febrile neutropenia. Baseline creatinine clearance was associated inversely with severe toxicity (P = 0.001). Although antitumor activity was observed, the frequent occurrence of severe toxicity with this regimen limited its clinical utility. Alternate schedules with a more favorable therapeutic index are undergoing clinical testing and should be pursued. The high level of toxicity observed with orally administered low dose 5-FU underscored the potency of eniluracil as a biochemical modulator.

Phase II trial of epirubicin, cisplatin, oral uracil and tegafur, and leucovorin in patients with advanced gastric carcinoma

The results of chemotherapy for patients with gastric carcinoma generally have been modest, although regimens developed more recently have produced higher response rates. One such regimen is epirubicin, cisplatin, and protracted infusion of 5-fluorouracil (ECF). The advantage of a long-term oral administration of uracil and tegafur (UFT) is that this treatment may be used to mimic the protracted infusion of 5-fluorouracil (5-FU). In addition, UFT treatment combined with leucovorin had a favorable activity and tolerable toxicity in patients with advanced gastric carcinoma. Instead of the inconvenience of an infusion pump and intravenous catheter for the protracted infusion of 5-FU, the authors administered UFT plus leucovorin in an ECF regimen for the treatment of patients with advanced gastric carcinoma. Fifty-two patients with advanced gastric carcinoma received epirubicin, cisplatin, and oral UFT plus leucovorin. Epirubicin 50 mg/m(2) and cisplatin 60 mg/m(2) were administered on Day 1 by intravenous injection. Tegafur and uracil 360 mg/m(2)/day orally was administered in conjunction with leucovorin administered at a fixed dose of 45 mg/day orally in divided daily doses for 21 days followed by a 7-day rest period. These courses were repeated every 4 weeks. The median age of the patients was 59 years with a median World Health Organization performance status of 1. Patients received a median of five courses of treatment (range, 1-10). Among the 47 patients evaluated, three patients achieved complete response, and 24 patients had partial responses, for an overall response rate of 57.5% (95% confidence interval, 71.5-43.3%). Stable disease was reported in 11 patients (23.4%), and another 9 patients (19.1%) showed disease progression. The median duration of survival was 15 months (range, 2-33+). The main toxicity was nausea/vomiting and neutropenia. Significant toxicity (modified National Cancer Institute common toxicity Grade 3 or 4) included neutropenia in 22 patients (42%), nausea in 14(27%), vomiting in 9 (18%), oral mucositis in 3 (6%), and diarrhea in 3 (6%) patients. The authors conclude that epirubicin, cisplatin, and oral UFT plus leucovorin, a convenient regimen, has a significant activity and tolerable toxicities in patients with gastric carcinoma.