A rare cause of susceptibility to neutropenic sepsis in a patient with metastatic pancreas cancer.
A 71-year-old patient receiving combination chemotherapy (irinotecan, oxaliplatin and 5-fluorouracil (5-FU)) for metastatic pancreas cancer was admitted after her first cycle of chemotherapy with a severe and unexpectedly prolonged episode of neutropenic sepsis associated with pancytopenia and marked mucositis. Owing to the unusual picture, the patient was tested for mutations in the gene encoding the enzyme dihydropyrimidine dehydrogenase (DPD)--an enzyme involved in the metabolism of the chemotherapy drug 5-FU. The patient was found to be heterozygous for a mutation, DPD IVS14+1G>A, leading to the severe toxicity exhibited following this regimen caused by delayed metabolism of 5-FU. She was treated aggressively with supportive care and recovered from this episode. Importantly she was subsequently switched to an alternative chemotherapy regimen to treat her disease. She continues to maintain an excellent quality of life some 9 months after her initial diagnosis on third-line chemotherapy.
Royal Free London NHS Foundation Trust, London, UK.
Beatriz
B
Suarez Martinez-Falero
Roopinder
R
Gillmore
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D064146:Chemotherapy-Induced Febrile Neutropenia / Q000235:genetics*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects* / Q000378:metabolism; D020022:Genetic Predisposition to Disease; D006801:Humans; D000077146:Irinotecan; D009154:Mutation; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D018805:Sepsis / Q000209:etiology*
D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil; D002166:Camptothecin