[Severe toxicity after treatment with capecitabine and fluorouracil due to partial dihydropyrimidine dehydrogenase deficiency].
Two female patients, aged 48 and 52 years, developed severe bone marrow suppression and (gastrointestinal) mucositis following administration of capecitabine. Analysis of the dihydropyrimidine dehydrogenase (DPD) activity in peripheral blood mononuclear cells revealed the presence of DPD deficiency. Both patients recovered in 3-4 weeks, and both had a (partial) remission of their tumours. Capecitabine is metabolised to 5-fluorouracil (5-FU) in the body. DPD-deficiency leads to impaired breakdown of 5-FU and hence to severe cytotoxicity following treatment with capecitabine or 5-FU. The most common mutation, IVS14 + 1G > A, is found in approximately 2% of the Dutch population. In case of unexpected severe toxicity during 5-FU or capecitabine treatment, DPD deficiency should be considered. Screening could be considered in view of the widespread use of capecitabine and 5-FU, the severe toxicity that may develop in patients with low DPD activity and the prevalence of the mutation.
Hooiveld
E A
EA
Afd. Medische Oncologie, Academisch Medisch Centrum/Universiteit van Amsterdam, Postbus 22.660, 1100 DD Amsterdam.
van Kuilenburg
A B
AB
Haanen
J B
JB
Westermann
A M
AM
D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D000069287:Capecitabine; D003841:Deoxycytidine / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000627:therapeutic use; D054067:Dihydropyrimidine Dehydrogenase Deficiency; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D009364:Neoplasm Recurrence, Local
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil