Dihydropyrimidine dehydrogenase activity during long-term adjuvant treatment with oral uracil and tegafur for colorectal cancer.

Abstract

BACKGROUND:

Dihydropyrimidine dehydrogenase (DPD) is a rate-limiting enzyme for the degradation of 5-fluorouracil. The effect of long-term treatment with oral fluoropyrimidines on DPD activity has not been investigated. This study was conducted to examine changes in DPD activity in peripheral mononuclear cells (PMNC) during long-term treatment with oral uracil and tegafur (UFT) for colorectal cancer.

METHODS:

UFT was administered for 5 consecutive days and not administered the next 2 days for 6 months after surgery. PMNC-DPD activity was measured before and 1, 2, 4 and 6 months after starting UFT administration.

RESULTS:

In 70 eligible patients, there were no significant variations of PMNC-DPD activity during postoperative administration of UFT for 6 months. Grade 2 or higher adverse events were observed in significantly more patients with low DPD than with high DPD activity (p = 0.018).

CONCLUSION:

There were no significant variations of PMNC-DPD activity during the postoperative administration of UFT for 6 months. Low PMNC-DPD activity before UFT treatment was considered to be a predicting factor for toxicity.

• Authors: Sotaro Sadahiro, Toshiyuki Suzuki, Yuji Maeda, Kenji Ishikawa, Yoichi Tanaka, Seiei Yasuda, Akemi Kamijo, Hiroyasu Makuuchi, Chieko Murayama
• Journal: Chemotherapy (Chemotherapy) Vol. 53 Issue 6 Pg. 442-5 ( 2007) ISSN: 1421-9794 [Electronic] Switzerland
• PMID: 17952005 (Publication Type: Journal Article)
• Copyright: (c) 2007 S. Karger AG, Basel.

Chemical References

• Tegafur
• Uracil
• Dihydrouracil Dehydrogenase (NADP)

Topics

• Administration, Oral
• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Chemotherapy, Adjuvant
• Colorectal Neoplasms (drug therapy, enzymology, pathology)
• Dihydrouracil Dehydrogenase (NADP) (metabolism)
• Female
• Humans
• Male
• Middle Aged
• Prospective Studies
• Tegafur (administration & dosage)
• Time Factors
• Uracil (administration & dosage)