Phase I trial of Orzel (UFT plus leucovorin), cisplatin, and radiotherapy in the treatment of potentially resectable esophageal cancer.

Tedesco KL, Berlin J, Blanke CD, Teng M, Choy H, Roberts J, Beauchamp RD, Leach S, Wyman K, Tarpley J, Shyr Y, Caillouette C, Chakravarthy B
Int J Radiat Oncol Biol Phys. 2005 61 (5): 1364-70

PMID: 15817338 · DOI:10.1016/j.ijrobp.2004.08.050

PURPOSE - 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.

CONCLUSION - 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.

MeSH Terms (16)

Adenocarcinoma Aged Antineoplastic Combined Chemotherapy Protocols Carcinoma, Squamous Cell Cisplatin Combined Modality Therapy Drug Combinations Esophageal Neoplasms Female Humans Leucovorin Male Middle Aged Radiation-Sensitizing Agents Tegafur Uracil

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