Prolonged severe 5-fluorouracil-associated neurotoxicity in a patient with dihydropyrimidine dehydrogenase deficiency

Nadine Shehata, Alan Pater, Shou-Ching Tang

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

5-Fluorouracil (5-FU) is an analogue of pyrimidine nucleosides that is widely used in the treatment of head and neck, breast, ovarian, and colon cancer. Stomatitis, diarrhea, dermatitis, and myelosuppression are the main toxicities of 5-FU. A less frequent side effect that is becoming more recognized is neurologic toxicity. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the catabolism of 5-FU. DPD deficiency follows an autosomal recessive pattern of inheritance, and its prevalence is estimated to be 3%. Cancer patients who are receiving 5-FU treatment and are DPD deficient can develop severe side effects. The neurologic toxicity can vary from being mild to severe and prolonged. We describe the side effects of 5- FU in a colon cancer patient who suffered severe mucositis, desquamating dermatitis, prolonged myelosuppression, and neurologic toxicity that required admission to the intensive care unit. The patient remained hospitalized for 3 months. Recovery from the side effects was complete 4 months after the last 5-FU treatment. Subsequent testing revealed that this patient has an extremely low level of DPD activity (0.015 nmol/min/mg protein; mean, 0.189 nmol/min/mg protein). Because neurologic toxicity is becoming more recognized and DPD affects the catabolism of 5-FU, we discuss management issues and the use of new DPD inhibitors. We also discuss whether screening for DPD deficiency is warranted to identify patients at risk for severe toxicities from 5-FU treatment.

Original languageEnglish (US)
Pages (from-to)201-205
Number of pages5
JournalCancer Investigation
Volume17
Issue number3
DOIs
StatePublished - Jan 1 1999

Fingerprint

Dihydropyrimidine Dehydrogenase Deficiency
Fluorouracil
Dihydrouracil Dehydrogenase (NADP)
Nervous System
Dermatitis
Colonic Neoplasms
Pyrimidine Nucleosides
Inheritance Patterns
Stomatitis
Mucositis
Therapeutics
Head and Neck Neoplasms
Ovarian Neoplasms
Intensive Care Units
Diarrhea
Proteins
Breast Neoplasms

Keywords

  • 5-Fluorouracil
  • Colon cancer chemotherapy
  • Dihydropyrimidine dehydrogenase deficiency
  • Neurotoxicity

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Prolonged severe 5-fluorouracil-associated neurotoxicity in a patient with dihydropyrimidine dehydrogenase deficiency. / Shehata, Nadine; Pater, Alan; Tang, Shou-Ching.

In: Cancer Investigation, Vol. 17, No. 3, 01.01.1999, p. 201-205.

Research output: Contribution to journalArticle

Shehata, Nadine ; Pater, Alan ; Tang, Shou-Ching. / Prolonged severe 5-fluorouracil-associated neurotoxicity in a patient with dihydropyrimidine dehydrogenase deficiency. In: Cancer Investigation. 1999 ; Vol. 17, No. 3. pp. 201-205.
@article{970e280ef7694d78b31143b6e6e4aaa7,
title = "Prolonged severe 5-fluorouracil-associated neurotoxicity in a patient with dihydropyrimidine dehydrogenase deficiency",
abstract = "5-Fluorouracil (5-FU) is an analogue of pyrimidine nucleosides that is widely used in the treatment of head and neck, breast, ovarian, and colon cancer. Stomatitis, diarrhea, dermatitis, and myelosuppression are the main toxicities of 5-FU. A less frequent side effect that is becoming more recognized is neurologic toxicity. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the catabolism of 5-FU. DPD deficiency follows an autosomal recessive pattern of inheritance, and its prevalence is estimated to be 3{\%}. Cancer patients who are receiving 5-FU treatment and are DPD deficient can develop severe side effects. The neurologic toxicity can vary from being mild to severe and prolonged. We describe the side effects of 5- FU in a colon cancer patient who suffered severe mucositis, desquamating dermatitis, prolonged myelosuppression, and neurologic toxicity that required admission to the intensive care unit. The patient remained hospitalized for 3 months. Recovery from the side effects was complete 4 months after the last 5-FU treatment. Subsequent testing revealed that this patient has an extremely low level of DPD activity (0.015 nmol/min/mg protein; mean, 0.189 nmol/min/mg protein). Because neurologic toxicity is becoming more recognized and DPD affects the catabolism of 5-FU, we discuss management issues and the use of new DPD inhibitors. We also discuss whether screening for DPD deficiency is warranted to identify patients at risk for severe toxicities from 5-FU treatment.",
keywords = "5-Fluorouracil, Colon cancer chemotherapy, Dihydropyrimidine dehydrogenase deficiency, Neurotoxicity",
author = "Nadine Shehata and Alan Pater and Shou-Ching Tang",
year = "1999",
month = "1",
day = "1",
doi = "10.3109/07357909909021422",
language = "English (US)",
volume = "17",
pages = "201--205",
journal = "Cancer Investigation",
issn = "0735-7907",
publisher = "Informa Healthcare",
number = "3",

}

TY - JOUR

T1 - Prolonged severe 5-fluorouracil-associated neurotoxicity in a patient with dihydropyrimidine dehydrogenase deficiency

AU - Shehata, Nadine

AU - Pater, Alan

AU - Tang, Shou-Ching

PY - 1999/1/1

Y1 - 1999/1/1

N2 - 5-Fluorouracil (5-FU) is an analogue of pyrimidine nucleosides that is widely used in the treatment of head and neck, breast, ovarian, and colon cancer. Stomatitis, diarrhea, dermatitis, and myelosuppression are the main toxicities of 5-FU. A less frequent side effect that is becoming more recognized is neurologic toxicity. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the catabolism of 5-FU. DPD deficiency follows an autosomal recessive pattern of inheritance, and its prevalence is estimated to be 3%. Cancer patients who are receiving 5-FU treatment and are DPD deficient can develop severe side effects. The neurologic toxicity can vary from being mild to severe and prolonged. We describe the side effects of 5- FU in a colon cancer patient who suffered severe mucositis, desquamating dermatitis, prolonged myelosuppression, and neurologic toxicity that required admission to the intensive care unit. The patient remained hospitalized for 3 months. Recovery from the side effects was complete 4 months after the last 5-FU treatment. Subsequent testing revealed that this patient has an extremely low level of DPD activity (0.015 nmol/min/mg protein; mean, 0.189 nmol/min/mg protein). Because neurologic toxicity is becoming more recognized and DPD affects the catabolism of 5-FU, we discuss management issues and the use of new DPD inhibitors. We also discuss whether screening for DPD deficiency is warranted to identify patients at risk for severe toxicities from 5-FU treatment.

AB - 5-Fluorouracil (5-FU) is an analogue of pyrimidine nucleosides that is widely used in the treatment of head and neck, breast, ovarian, and colon cancer. Stomatitis, diarrhea, dermatitis, and myelosuppression are the main toxicities of 5-FU. A less frequent side effect that is becoming more recognized is neurologic toxicity. Dihydropyrimidine dehydrogenase (DPD) is the rate-limiting enzyme in the catabolism of 5-FU. DPD deficiency follows an autosomal recessive pattern of inheritance, and its prevalence is estimated to be 3%. Cancer patients who are receiving 5-FU treatment and are DPD deficient can develop severe side effects. The neurologic toxicity can vary from being mild to severe and prolonged. We describe the side effects of 5- FU in a colon cancer patient who suffered severe mucositis, desquamating dermatitis, prolonged myelosuppression, and neurologic toxicity that required admission to the intensive care unit. The patient remained hospitalized for 3 months. Recovery from the side effects was complete 4 months after the last 5-FU treatment. Subsequent testing revealed that this patient has an extremely low level of DPD activity (0.015 nmol/min/mg protein; mean, 0.189 nmol/min/mg protein). Because neurologic toxicity is becoming more recognized and DPD affects the catabolism of 5-FU, we discuss management issues and the use of new DPD inhibitors. We also discuss whether screening for DPD deficiency is warranted to identify patients at risk for severe toxicities from 5-FU treatment.

KW - 5-Fluorouracil

KW - Colon cancer chemotherapy

KW - Dihydropyrimidine dehydrogenase deficiency

KW - Neurotoxicity

UR - http://www.scopus.com/inward/record.url?scp=0033036589&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033036589&partnerID=8YFLogxK

U2 - 10.3109/07357909909021422

DO - 10.3109/07357909909021422

M3 - Article

C2 - 10099659

AN - SCOPUS:0033036589

VL - 17

SP - 201

EP - 205

JO - Cancer Investigation

JF - Cancer Investigation

SN - 0735-7907

IS - 3

ER -