5-Fluorouracil Chemotherapy for Dihydropyrimidine Dehydrogenase-deficient Patients: Potential of the Dose-escalation
Yoichiro Yoshida1, Kenichiro Ogura2, Akira Hiratsuka2
1Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan yy4160@yahoo.co.jp.
Background:
Dihydropyrimidine dehydrogenase (DPD) degrades approximately 85% of administered 5-fluorouracil (5-FU). With a reported high mortality rate, chemotherapy is generally contraindicated for patients with DPD deficiency.
Patients And Methods:
Chemotherapy was initiated for a 73-year-old man with DPD deficiency. Capecitabine was administered in incrementally increasing doses, beginning with a single pill while monitoring plasma 5-FU concentration, and neutrophil and platelet counts.
Results:
DPD protein level was 2.35 U/mg. After increasing the capecitabine dose to 1,800 mg, oxaliplatin and bevacizumab were added. Subsequent DPD protein measurement showed that the level had increased to approximately 12-fold the one before chemotherapy. Sequencing of all 23 exons of DPYD gene revealed a mutation of guanine to thymine in exon 11 (1156 G>T).
Conclusion:
This is the first report to indicate that DPD activity can be induced. These findings may provide early indications of a new method for chemotherapy for DPD-deficient patients.
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