title: Phase I study of oral uracil and Tegafur plus leucovorin and pelvic radiation in patients with recurrent rectal cancer.
abstract: Continuous 5-fluorouracil (5-FU) infusion during radiation therapy is superior to the application of bolus 5-FU schedules. As an oral therapy, that provides prolonged fluoropyrimidine exposure, uracil and Tegafur (UFT) plus leucovorin (LV) has shown favorable activity with only moderate toxicity in colorectal cancer. The present study was designed to evaluate the safety of UFT+LV combined with pelvic radiation to determine the maximum-tolerated dose (MTD) in recurrent rectal cancer. Patients with recurrent rectal cancer received escalating doses of UFT (starting at 250 mg/m /day with 50 mg/m /day increments between consecutive cohorts) and fixed doses of LV (90 mg). The UFT+LV combination was given 5 days per week simultaneously to a 5-week course of irradiation up to a total dose of 50.4 Gy, 1.8 Gy daily fractions followed by a boost of 5.4 or 9.0 Gy to the gross tumor volume. Nineteen patients were treated and 14 received the full chemotherapy with delivery of all planned radiotherapy. The MTD of UFT was 400 mg/m /day due to the occurrence of dose-limiting diarrhea and emesis. Toxicities were mild and manageable on the lower dose levels. Treatment was feasible mainly on an outpatient base. We conclude that combined chemoradiation with oral UFT+LV is feasible and well tolerated for recurrent rectal cancer patients undergoing pelvic radiation. The safety profile appears comparable to that of i.v. dosing without requiring any i.v. port systems. The recommended doses for further phase II chemoradiation trials are 350 mg/m /day UFT+90 mg LV.
authors.affiliation: Department of Radio-Oncology and Radiotherapy, Klinikum Braunschweig, 38114 Braunschweig, Germany. m.schiebe@klinikum-braunschweig.de
authors.forename: Martina E
authors.initials: ME
authors.lastname: Schiebe
authors.forename: Thomas
authors.initials: T
authors.lastname: Reese
authors.forename: Frederik
authors.initials: F
authors.lastname: Wenz
authors.forename: Heinz
authors.initials: H
authors.lastname: Schmidberger
authors.forename: Rita
authors.initials: R
authors.lastname: Engenhart-Cabillic
authors.forename: Jürgen
authors.initials: J
authors.lastname: Dunst
authors.forename: Clemens F
authors.initials: CF
authors.lastname: Hess
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hoffmann
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D010388:Pelvis / Q000528:radiation effects*; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D005641:Tegafur; D014498:Uracil; D002955:Leucovorin