Dihydropyrimidine Dehydrogrnase Deficiency with Severe Adverse Events Caused by XELOX+Bevacizumab

Abstract

A 64-year-old woman with rectal cancer underwent laparoscopic low anterior resection. Postoperative diagnosis was fStage IV (moderately differentiated adenocarcinoma (tub2), pT2 (MP), pN2 (6/15), cH1, cP0, cM0, EGFR (+), K-RAS mutation). Chemotherapy with XELOX+Bevacizumab (Bev) was started on post operative days 32, but capecitabin intake was stopped on the 11th day due to grade 2 diarrhea and vomiting from the 9th day of initiating chemotherapy. She then suffered grade 4 leukocytopenia, grade 4 thrombocytopenia, grade 2 fever, grade 3 diarrhea and vomiting. Hematotoxicity was improved by the administration of G-CSF and platelet transfusion in addition to antibiotics and antimycotics, while diarrhea and vomiting continued and the drug-induced enteritis with cytomegalovirus enteritis was diagnosed. After the general state improvement, partial hepatectomy was performed and chemotherapy with CPT-11+Bev was conducted, but she died with progression of disease fifteen months after the first operation. The dihydropyrimidine dehydrogenase (DPD) activity in pheral mononuclear blood cells showed remarkably low, so this case was diagnosed as DPD deficiency. DPD deficiency is very rare, and no diagnosis nor screening system has been established for its detection. In DPD deficiency, 5-fluorouracil can lead to severe and sometimes life-threatening adverse events, therefore prompt and adequate treatment must be considered for this condition.