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

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/m2 (Days 1 and 22) and UFT with leucovorin orally on Days 1–35. UFT was escalated in 50-mg/m2 increments, starting at 200 mg/m2/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/m2/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/m2/d given orally in two divided doses when given with leucovorin, cisplatin, and radiotherapy. [Copyright &y& Elsevier]