Pilot Study of Heptaplatin, UFT-E and Leucovorin in Advanced Gastric Carcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Heptaplatin (SKI-2053R, Sunpla ), a new platinum analogue which has a better toxicity profile than cisplatin, has been used with 5-fluorouracil (5-FU) continuous infusion for the treatment of advanced gastric carcinoma. However, continuous 5-FU infusion had a inconvenience to administration. The aim of this study was to evaluate the efficacy and toxicity of heptaplatin, UFT-E and leucovorin combination chemotherapy in advanced gastric cancer. MATERIALS AND METHODS: A total of 22 patients was enrolled in this study at Kyung Hee University and Korea University from September 1999 to May 2001. Heptaplatin 400 mg/m2 was given as intravenous infusion for 1 hour at day 1. Oral UFT-E 360 mg/m2 and leucovorin 45 mg/day were administered for 21 consecutive days followed by a 7-day drug free interval. This schedule was repeated every 4 weeks. RESULTS: The 22 enrolled patients received 81 courses of chemotherapy and the median number of course per patient was three with a range of one to six. Five of 21 patients achieved partial responses (23.8%; 95% confidence interval, 5.6% to 42%) without complete response. Out of the 5 responding patients, three had unresectable perigastric lymph-nodes, one patient had a ovarian metastasis, and one patient had a peritoneal metastasis respectively. Main toxicities were neutropenia and nausea/vomiting. Grade 3 and 4 neutropenia were observed in 4 patients (18%) and grade 3 nausea/vomiting were observed in 5 patients (22.7%). The median time to progression was 4 months (range, 0.5 to 13 months), and median survival duration was 7.5 months (range, 2.0 to 14 months). Median response duration was 5.0 months (range, 1.5 to 10 months). CONCLUSION: A combination chemotherapy of heptaplatin, UFT-E and leucovorin has a comparable efficacy with those of previously reported heptaplatin and intravenous regimen of 5-FU and controllable toxicity in advanced gastric carcinoma. Further study with large patient population is warranted to determine the usefulness of this regimen.

Phase II Trial of Gemcitabine, UFT-E, Leucovorin Combination Chemotherapy in Advanced Pancreatic Adenocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To evaluate the efficacy and toxicity of a Gemcitabine, UFT-E, Leucovorin combination chemotherapy in the treatment of advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Patients <=70 years, with no prior chemotherapy and with bidimensionally measurable advanced pancreatic adenocarcinoma, ECOG performance status <=2, and adequate bone marrow, kidney, and liver function were eligible for this trial. Eligibility criteria for clinical benefit assessment were pain with at least a daily analgesic consumption of two nonsteroidal anti-inflammatory drugs or a Karnofsky performance status between 50 and 70. Treatment consisted of 1,000 mg/m2 of Gemcitabine on days 1, 8 and 15, repeated every 4 weeks, with UFT-E administered orally 500 mg-700 mg by body surface area (BSA). Leucovorin was administered 45 mg/day orally. Dosages of UFT-E and Leucovorin were divided and administered three times per day from day 1 to day 21. After 7 days of rest, UFT-E and Leucovorin were administered repeatedly. RESULTS: Twenty-three patients were enrolled between April 1999 to April 2000. Eighty two cycles (median, four cycles) were delivered to all patients. The objective response rate was 15.8% in 19 assessable patients and 13.0% in the intent-to-treat population. Twelve patients (57.9%) displayed stable disease. Grade 3 or 4 neutropenia occurred in 30.4% of patients, nausea/vomiting in 8.3%, diarrhea in 4.3%, and mucositis in 4.3%. The median time to progression was 8 months. The median survival was 8 months in the assessable population and 6 months in the intent-to-treat population Clinical benefit was achieved in 11 (57.9%) of 19 assessable patients. CONCLUSION: Gemcitabine, UFT-E, Leucovorin combination chemotherapy is a well-tolerated and safe regimen in cases of advanced pancreatic adenocarcinoma. Although the response rate is low, it shows a survival benefit and clinical benefit and deserves further evaluation in a phase III trial.

A Phase II Trial of UFT-E and Oral Leucovorin in Advanced Colorectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To determine the efficacy and toxicity of UFT-E plus oral calcium leucovorin in the treatment of patients with advanced colorectal cancer. MATERIALS AND METHODS: Forty-three patients with advanced, bidimensionally measurable colorectal adenocarcinoma were enrolled in the trial. No patients had received prior palliative chemotherapy. The patients that had received previous adjuvant chemotherapy were enrolled when more than 6 months had elapsed after the completion of adjuvant therapy. Patients were treated with 300 mg/m2/day of UFT-E (tegafur-based) plus 90 mg/day of leucovorin administered orally in three divided daily doses, every 8 hours for 28 days followed by a 7-day rest period. Response was evaluated after two or three courses of therapy. RESULTS: Thirty-six of forty-three patients were evaluable for response; seven dropped out due to infection, toxicity and patients' refusal. Ten patients had partial responses and one patient complete response (response rate, 31%; 95% confidence interval, 16~46%). The median response duration for the UFT-E plus leucovorin regimen was 28 weeks. Grade III toxicity was seen in one case, with diarrhea. CONCLUSION: This oral regimen proved effective and well tolerated. This schema also avoided inconveniences, such as hospitalization and the use of infusion pumps, which are associated with 5-FU infusion regimens. The regimen used showed minimal toxicity, especially in the upper digestive tract, with good patient compliance.

Toxicity Evaluation of Oral Adjuvant Chemotherapeutic Drugs UFT Versus UFT-E in the Colorectal Cancer

PURPOSE: Oral UFT is known to be a safe and effective antineoplastic regimen for adjuvant chemotherapy of colorectal cancer. As it sometimes produces upper gastrointestinal symptoms such as anorexia, nausea, vomiting and abdominal pain, medication should be stopped transiently or dosage reduced. UFT-E, an enteric coated granule of UFT was introduced to reduce UGI toxicity. We analyzed the toxicity of UFT and UFT-E prospectively for the purpose of comparison between the two types. METHODS: The toxicity of UFT and UFT-E were evaluated in 83 patients (UFT; 45, UFT-E; 38) with colorectal cancer who underwent curative surgery according to the WHO toxicity criteria. All patients were selected consecutively with patients' approval and by the "Institutional Review Board, Asan Medical Center". RESULTS: The toxicity incidence in UFT-E group was slightly less than that in UFT group without statistical significance. The severity of toxicity seemed to be mild within grade 1 or 2 and most of them toxicity self-limiting. The regimen was completely interrupted in 9 patients (20%) in the UFT group, 3 patients (7.9%) in the UFT-E group due to severe UGI symptoms, prolonged leukopenia, derrangement of liver function and skin rash. CONCLUSIONS: Toxicity rate of UFT-E was not higher than that of UFT. But we cannot prove superiority of UFT-E on UGI toxicity. Oral UFT-E can be administered safely on an outpatient basis without lethal toxicity requiring hospitalization.