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J Clin Pathol 2005;58:553-555 doi:10.1136/jcp.2004.022319
  • Short reports/Case reports

5-Fluorouracil/irinotecan induced lethal toxicity as a result of a combined pharmacogenetic syndrome: report of a case

  1. M Steiner1,
  2. M Seule1,
  3. B Steiner2,
  4. I Bauer3,
  5. M Freund2,
  6. C H Köhne2,
  7. P Schuff-Werner1
  1. 1Institute of Clinical Chemistry and Laboratory Medicine, University of Rostock, Ernst-Heydemann-Str. 6, D-18057 Rostock, Germany
  2. 2Division of Haematology/Oncology, Department of Internal Medicine, University of Rostock
  3. 3Division of Medical Genetics, Children’s Hospital, University of Rostock
  1. Correspondence to:
 Dr M Steiner
 Medical Faculty, Institute of Clinical Chemistry and Laboratory Medicine, University of Rostock, Ernst-Heydemann-Str. 6, D-18057 Rostock, Germany; michael.steinermed.uni-rostock.de
  • Accepted 22 September 2004

Abstract

Combination cancer chemotherapy induced toxicity can be associated with combined pharmacogenetic syndromes. Dihydropyrimidine dehydrogenase (DPD) is the principal enzyme involved in the catabolic detoxification of 5-fluorouracil (5FU). A heterozygous G > A transition at the 5′ splicing donor consensus sequence in intron 14 leading to exon 14 skipping (IVS14+1 G > A, DPYD*2A) with partial loss of enzyme activity may be partly responsible for 5FU induced toxicity, whereas irinotecan associated toxicity may in part be explained by an aberrant UGT1A1 promoter (TA)n genotype underlying Gilbert’s syndrome with reduced liver glucuronidation activity. This report describes a 44 year old white woman who suffered from severe gastrointestinal and haematological toxicity while undergoing 5FU24h/folinic acid/irinotecan treatment for adenocarcinoma of the sigmoid colon. Despite appropriate supportive treatment, her condition rapidly deteriorated and led to death. Molecular analysis revealed a hitherto undescribed combined pharmacogenetic syndrome, consisting of heterozygosity for the DPD IVS14+1 G > A mutation and UGT1A1 (TA)6/7 heterozygosity, which probably contributed to the fatal outcome in this patient.

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  • Full permission was given for this case report to be published.

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