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

Abstract

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.

• Authors: Karen L Tedesco, Jordan Berlin, Charles D Blanke, Ming Teng, Hak Choy, John Roberts, R Daniel Beauchamp, Steve Leach, Ken Wyman, John Tarpley, Yu Shyr, Carol Caillouette, Bapsi Chakravarthy
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 61 Issue 5 Pg. 1364-70 (Apr 01 2005) ISSN: 0360-3016 [Print] United States
• PMID: 15817338 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Drug Combinations
• Radiation-Sensitizing Agents
• UFT(R) drug
• Tegafur
• Uracil
• Cisplatin
• Leucovorin

Topics

• Adenocarcinoma (drug therapy, radiotherapy)
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Squamous Cell (drug therapy, radiotherapy)
• Cisplatin (administration & dosage)
• Combined Modality Therapy
• Drug Combinations
• Esophageal Neoplasms (drug therapy, radiotherapy)
• Female
• Humans
• Leucovorin (administration & dosage)
• Male
• Middle Aged
• Radiation-Sensitizing Agents (therapeutic use)
• Tegafur (administration & dosage, adverse effects)
• Uracil (administration & dosage, adverse effects)