Yoichiro Yoshida1, Kenichiro Ogura2, Akira Hiratsuka2, Naoya Aisu3, Teppei Yamada3, Daibo Kojima3, Syu Tanimura3, Kentaro Ogata4, Shuuji Hara4, Ai Mogi5, Yasushi Takamatsu5, Kazuo Tamura5, Hideyuki Mishima6, Yuichi Yamashita3. 1. Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan yy4160@yahoo.co.jp. 2. Department of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan. 3. Department of Gastroenterological Surgery, Faculty of Medicine, Fukuoka University, Fukuoka, Japan. 4. Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan. 5. Department of Internal Medicine, Division of Oncology, Hematology and Infectious Diseases, Fukuoka University, Fukuoka, Japan. 6. Cancer Center, Aichi Medical University, Nagakute, Japan.
Abstract
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. Copyright
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-deficientpatients. Copyright