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International Cancer Conference Journal

, Volume 7, Issue 4, pp 125–129 | Cite as

Severe adverse events due to dihydropyrimidine dehydrogenase deficiency in a Japanese patient with colon cancer taking capecitabine: a case report

  • Mai Tsutsui
  • Seiichiro Yamamoto
  • Yusuke Yoshikawa
  • Ryo Nakanishi
  • Kiminori Takano
  • Koji Osumi
  • Tomotaka Akatsu
  • Kimiyasu Yoneyama
  • Motohito Nakagawa
  • Toshio Kanai
Case report

Abstract

Fluoropyrimidine has been commonly used not only in unresectable cases of metastatic colorectal cancer, but also in adjuvant therapy. Dihydropyrimidine dehydrogenase (DPD) is an enzyme encoded by the DPYD gene, which is responsible for the rate-limiting step in pyrimidine catabolism and breaks down more than 80% of standard doses of 5-fluorouracil (5-FU) and capecitabine, an oral prodrug of 5-FU. The lack of enzymatic activity increases the half-life of the drug, resulting in excess drug accumulation and toxicity which may lead to life-threatening side effects. There have been several published case reports about DPD deficiency in patients with colorectal cancer in Western countries. However, case reports of DPD deficiency in Japanese patients with colorectal cancer are rare because measuring DPD activity is not covered by public medical insurance in Japan, and it is not examined in our daily clinical practice currently. Therefore, we think that it is important to accumulate such case reports for further understanding. This report describes the case of a Japanese patient with colon cancer who experienced severe side effects while taking capecitabine, due to DPD deficiency. A 68-year-old man with ascending colon cancer underwent curative laparoscopic right hemicolectomy. Because final pathologic staging was Stage IIIa, standard adjuvant chemotherapy with capecitabine (3600 mg/body/day, days 1–14, every 3 weeks) was started on postoperative day 50. After 2 weeks, he started to experience Grade 3 diarrhea and was admitted to the hospital on postoperative day 66. On day 70, the patient had Grade 4 febrile neutropenia. Antibiotics and granulocyte-colony-stimulating factor were administered until his blood tests recovered to the normal degree. After 1 week of diarrhea, antidiarrheal agents were administered, and the patient gradually recovered. During the occurrence of diarrhea, specimen cultures were negative for infection. He was discharged on day 21 of the hospital stay. DPD deficiency was suspected, and 2 weeks later the DPD activity of the peripheral blood mononucleocytes was examined. The result was 10.3 U/mg protein which was remarkedly low (reference range 22.6–183.6 U/mg protein), and DPD deficiency was diagnosed. We always must consider the possibility of DPD deficiency in patients who experience severe side effects while taking capecitabine.

Keywords

Fluoropyrimidines Dihydropyrimidine dehydrogenase deficiency Colon cancer Capecitabin Side effects 

Abbreviations

5FU

5-fluorouracil

JSCCR

Japanese Society for Cancer of the Colon and Rectum

CTCAE

Common Terminology Criteria for Adverse Events

WBC

White cell count

CRP

C-reactive protein

MEPM

Meropenem

G-CSF

Granulocyte-colony stimulating factor

CT

Computed tomography

LVFX

Levofloxacin

ELISA

Enzyme-linked immunosorbent assay

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

Informed consent

Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

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Copyright information

© The Japan Society of Clinical Oncology 2018
corrected publication July 2018

Authors and Affiliations

  • Mai Tsutsui
    • 1
  • Seiichiro Yamamoto
    • 1
  • Yusuke Yoshikawa
    • 1
  • Ryo Nakanishi
    • 1
  • Kiminori Takano
    • 1
  • Koji Osumi
    • 1
  • Tomotaka Akatsu
    • 1
  • Kimiyasu Yoneyama
    • 1
  • Motohito Nakagawa
    • 1
  • Toshio Kanai
    • 1
  1. 1.Department of SurgeryHiratsuka City HospitalHiratsukaJapan

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