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Cardiotoxicity of 5-fluorouracil and capecitabine in a pancreatic cancer patient with a novel mutation in the dihydropyrimidine dehydrogenase gene.
JOP 2009; 10(2):215-20JOP

Abstract

CONTEXT

5-fluorouracil (5-FU) is an antimetabolite that acts during the S phase of the cell cycle. Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the pathway that catabolises the pyrimidines. 5-fluorouracil and its oral prodrug capecitabine are used in the treatment of a number of solid tumors, including colorectal, breast, gastric, pancreatic, prostate, and bladder cancers. Common side effects include leukopenia, diarrhea, stomatitis, nausea, vomiting, and alopecia. Cardiotoxicity is a relatively uncommon side effect of 5-fluorouracil and capecitabine.

CASE REPORT

This article reports the case of a 63-year-old male with locally invasive pancreatic cancer who developed recurrent chest pain and ischemic electrocardiogram changes after treatment with 5-fluorouracil and capecitabine. Full sequencing of the dihydropyrimidine dehydrogenase (DPYD) gene and analysis of the thymidylate synthetase (TYMS) gene promoter region was performed. Pharmacogenetic testing revealed p453L (1358C>T) type DPYD germ line mutation. This mutation has not been reported previously in association with 5-fluorouracil induced cardiotoxicity.

CONCLUSION

Cardiotoxicity associated with 5-fluorouracil and capecitabine administration is infrequently reported in the literature and appears to be dose and schedule dependent. Genetic variations such as polymorphic abnormality of DPYD are potential causative factors for a significant portion of serious adverse reactions to 5-fluorouracil-based therapy.

Authors

No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Case Reports
Letter

Language

eng

PubMed ID

19287123

Citation

Shahrokni, Armin, et al. "Cardiotoxicity of 5-fluorouracil and Capecitabine in a Pancreatic Cancer Patient With a Novel Mutation in the Dihydropyrimidine Dehydrogenase Gene." JOP : Journal of the Pancreas, vol. 10, no. 2, 2009, pp. 215-20.
Shahrokni A, Rajebi MR, Harold L, et al. Cardiotoxicity of 5-fluorouracil and capecitabine in a pancreatic cancer patient with a novel mutation in the dihydropyrimidine dehydrogenase gene. JOP. 2009;10(2):215-20.
Shahrokni, A., Rajebi, M. R., Harold, L., & Saif, M. W. (2009). Cardiotoxicity of 5-fluorouracil and capecitabine in a pancreatic cancer patient with a novel mutation in the dihydropyrimidine dehydrogenase gene. JOP : Journal of the Pancreas, 10(2), pp. 215-20.
Shahrokni A, et al. Cardiotoxicity of 5-fluorouracil and Capecitabine in a Pancreatic Cancer Patient With a Novel Mutation in the Dihydropyrimidine Dehydrogenase Gene. JOP. 2009 Mar 9;10(2):215-20. PubMed PMID: 19287123.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cardiotoxicity of 5-fluorouracil and capecitabine in a pancreatic cancer patient with a novel mutation in the dihydropyrimidine dehydrogenase gene. AU - Shahrokni,Armin, AU - Rajebi,Mohammad Reza, AU - Harold,Laurie, AU - Saif,Muhammad Wasif, Y1 - 2009/03/09/ PY - 2009/3/17/entrez PY - 2009/3/17/pubmed PY - 2009/5/30/medline SP - 215 EP - 20 JF - JOP : Journal of the pancreas JO - JOP VL - 10 IS - 2 N2 - CONTEXT: 5-fluorouracil (5-FU) is an antimetabolite that acts during the S phase of the cell cycle. Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the pathway that catabolises the pyrimidines. 5-fluorouracil and its oral prodrug capecitabine are used in the treatment of a number of solid tumors, including colorectal, breast, gastric, pancreatic, prostate, and bladder cancers. Common side effects include leukopenia, diarrhea, stomatitis, nausea, vomiting, and alopecia. Cardiotoxicity is a relatively uncommon side effect of 5-fluorouracil and capecitabine. CASE REPORT: This article reports the case of a 63-year-old male with locally invasive pancreatic cancer who developed recurrent chest pain and ischemic electrocardiogram changes after treatment with 5-fluorouracil and capecitabine. Full sequencing of the dihydropyrimidine dehydrogenase (DPYD) gene and analysis of the thymidylate synthetase (TYMS) gene promoter region was performed. Pharmacogenetic testing revealed p453L (1358C>T) type DPYD germ line mutation. This mutation has not been reported previously in association with 5-fluorouracil induced cardiotoxicity. CONCLUSION: Cardiotoxicity associated with 5-fluorouracil and capecitabine administration is infrequently reported in the literature and appears to be dose and schedule dependent. Genetic variations such as polymorphic abnormality of DPYD are potential causative factors for a significant portion of serious adverse reactions to 5-fluorouracil-based therapy. SN - 1590-8577 UR - https://www.unboundmedicine.com/medline/citation/19287123/Cardiotoxicity_of_5_fluorouracil_and_capecitabine_in_a_pancreatic_cancer_patient_with_a_novel_mutation_in_the_dihydropyrimidine_dehydrogenase_gene_ L2 - http://www.joplink.net/prev/200903/15.html DB - PRIME DP - Unbound Medicine ER -