title: Phase I trial of Orzel (UFT plus leucovorin), cisplatin, and radiotherapy in the treatment of potentially resectable esophageal cancer.
abstract: OBJECTIVE
  Fluorinated pyrimidines have been established as radiosensitizers in the combined modality therapy of esophageal cancer. UFT, an oral combination of a 5-fluorouracil pro-drug (uracil) and a dihydropyrimidine dehydrogenase inhibitor (ftorafur), may provide improvement in the ease of administration with equal efficacy. This Phase I study was designed to determine the maximal tolerated dose and dose-limiting toxicity of UFT, leucovorin, and cisplatin when given with radiotherapy in the neoadjuvant treatment of resectable esophageal cancer.
  
  
  METHODS
  Chemotherapy consisted of i.v. cisplatin 80 mg/m(2) (Days 1 and 22) and UFT with leucovorin orally on Days 1-35. UFT was escalated in 50-mg/m(2) increments, starting at 200 mg/m(2)/d. Radiotherapy consisted of 4500 cGy in 25 fractions. Patients underwent resection 4-6 weeks after chemoradiotherapy.
  
  
  RESULTS
  Ten patients with resectable esophageal cancer were enrolled. Of the 7 patients entered at dose level 1, 1 developed a dose-limiting toxicity of nausea. All 3 patients entered at dose level 2 developed dose-limiting toxicity. The maximal tolerated dose for UFT was the starting level, 200 mg/m(2)/d. Of the 10 patients enrolled, 8 underwent esophagectomy and 2 developed progressive disease and did not undergo surgery. The disease of 6 of the 8 patients was downstaged at surgery.
  
  
  CONCLUSIONS
  The recommended UFT dose for Phase II studies is 200 mg/m(2)/d given orally in two divided doses when given with leucovorin, cisplatin, and radiotherapy.
authors.affiliation: Department of Oncology, Vanderbilt University School of Medicine and Veteran's Affairs Medical Center, Nashville, TN, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Tedesco
authors.forename: Jordan
authors.initials: J
authors.lastname: Berlin
authors.forename: Charles D
authors.initials: CD
authors.lastname: Blanke
authors.forename: Ming
authors.initials: M
authors.lastname: Teng
authors.forename: Hak
authors.initials: H
authors.lastname: Choy
authors.forename: John
authors.initials: J
authors.lastname: Roberts
authors.forename: R Daniel
authors.initials: RD
authors.lastname: Beauchamp
authors.forename: Steve
authors.initials: S
authors.lastname: Leach
authors.forename: Ken
authors.initials: K
authors.lastname: Wyman
authors.forename: John
authors.initials: J
authors.lastname: Tarpley
authors.forename: Yu
authors.initials: Y
authors.lastname: Shyr
authors.forename: Carol
authors.initials: C
authors.lastname: Caillouette
authors.forename: Bapsi
authors.initials: B
authors.lastname: Chakravarthy
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000532:radiotherapy; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004338:Drug Combinations; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011838:Radiation-Sensitizing Agents / Q000627:therapeutic use*; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D014498:Uracil / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D004338:Drug Combinations; D011838:Radiation-Sensitizing Agents; C096910:UFT(R) drug; D005641:Tegafur; D014498:Uracil; D002945:Cisplatin; D002955:Leucovorin