A phase I study of combined UFT plus leucovorin and radiotherapy for pancreatic cancer.

Abstract

PURPOSE:

This Phase I study combines tegafur and uracil (UFT) with leucovorin and conventional radiation for the treatment of pancreatic cancer. The design seeks to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of this regimen as well as to define a future Phase II dose level.

METHODS:

Patients with locally advanced and unresectable pancreatic cancer were treated with 45 Gy of radiation therapy. The initial UFT dose was 150 mg/m(2)/day given with leucovorin 90 mg/day, both divided into 3 daily doses for 35 days concurrent with radiation. UFT doses were escalated at increments of 50 mg/m(2)/day. Dose-limiting toxicity (DLT) was defined as Grade 3 or greater nausea, vomiting or diarrhea despite medical intervention; or Grade 3 or greater neutropenia/thrombocytopenia; or Grade 3 or greater hepatic toxicity; or inability of the patient to take 75% or more of the planned UFT/leucovorin; or radiotherapy interruption of greater than 1 week. The MTD for UFT/leucovorin was exceeded by one dose level when a certain dose caused DLT in 2 or more patients of 6.

RESULTS:

Five evaluable patients had Stage I resectable disease but had pathologic adenopathy. Seven had Stage II unresectable disease. Compliance with therapy was excellent. At a daily dose of 300 mg/m(2) of UFT, we noticed minimal diarrhea and hematologic toxicity with mild-moderate nausea, anorexia, and fatigue. Three patients had Grade 4 toxicity: 1 had neutropenia on Day 38, 1 had diarrhea on Day 55, and 1 had vomiting on Day 15.

CONCLUSION:

Oral UFT/leucovorin and radiation therapy offers patients a viable treatment option for pancreatic cancer. The major known toxicity of diarrhea was tolerable. The MTD was not reached in this study. Our current plan is to expand this into a Phase I/II trial beginning at a UFT dose of 300 mg/m(2) and correlate this with clinical pharmacologic parameters. The potential benefit of long bioavailability and oral delivery of UFT compares favorably with continuous infusion regimens without the added morbidity of a catheter and pump.

• Authors: H A Childs 3rd, S A Spencer, D Raben, J A Bonner, J Newsome, F Robert
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 47 Issue 4 Pg. 939-44 (Jul 01 2000) ISSN: 0360-3016 [Print] United States
• PMID: 10863063 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)

Chemical References

• Tegafur
• Uracil
• Leucovorin

Topics

• Adenocarcinoma (drug therapy, pathology, radiotherapy)
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Combined Modality Therapy
• Diarrhea (etiology)
• Female
• Humans
• Leucovorin (administration & dosage, adverse effects)
• Male
• Middle Aged
• Neutropenia (etiology)
• Pancreatic Neoplasms (drug therapy, pathology, radiotherapy)
• Tegafur (administration & dosage, adverse effects)
• Uracil (administration & dosage, adverse effects)