Phase I trial of Orzel (UFT plus leucovorin), cisplatin, and radiotherapy in the treatment of potentially resectable esophageal cancer.
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.
Tedesco
Karen L
KL
Department of Oncology, Vanderbilt University School of Medicine and Veteran's Affairs Medical Center, Nashville, TN, USA.
Berlin
Jordan
J
Blanke
Charles D
CD
Teng
Ming
M
Choy
Hak
H
Roberts
John
J
Beauchamp
R Daniel
RD
Leach
Steve
S
Wyman
Ken
K
Tarpley
John
J
Shyr
Yu
Y
Caillouette
Carol
C
Chakravarthy
Bapsi
B
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
D004338:Drug Combinations; D011838:Radiation-Sensitizing Agents; C096910:UFT(R) drug; D005641:Tegafur; D014498:Uracil; D002945:Cisplatin; D002955:Leucovorin