Irinotecan cytotoxicity does not necessarily depend on the UGT1A1 polymorphism but on fluoropyrimidine: a molecular case report.
We have previously demonstrated that the combined use of doxifluridine and irinotecan shows a different molecular mechanism than that of the protracted venous infusion of 5-FU and irinotecan. In this analysis, there is a suggestion that doxifluridine may enhance irinotecan and enable us to decrease the dose of irinotecan without losing the strong effect by using doxifluridine instead of 5-FU. We present a colon cancer patient with the UGT1A1 polymorphism (UGT1A1 *28) as a known high risk for irinotecan, who was treated with a combination of doxifluridine and irinotecan for peritoneal dissemination resulting in stable disease for 2 years without adverse reactions, although the patient initially developed severe adverse effects to the combination of the protracted venous infusion of 5-FU and irinotecan. Even with the same ratios of fluoropyrimidine and irinotecan combinations, replacing 5-FU with doxifluridine or capecitabine could provide new strategies to obtain not only convenience but also better efficacy and safety at the molecular level.
Inoue
Yasuhiro
Y
Division of Reparative Medicine, Department of Gastrointestinal and Pediatric Surgery, Institute of Life Sciences, Mie University Graduate School of Medicine, Mie 514-8507, Japan.
Miki
Chikao
C
Watanabe
Hideki
H
Hiro
Junichiro
J
Toiyama
Yuji
Y
Ojima
Eiki
E
Nakatani
Kaname
K
Nobori
Tsutomu
T
Kusunoki
Masato
M
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics*; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000009:adverse effects; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D014453:Glucuronosyltransferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D000077146:Irinotecan; D011110:Polymorphism, Genetic; D000099148:UGT1A1 Enzyme
D002166:Camptothecin; D005467:Floxuridine; D005472:Fluorouracil; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme; C025034:doxifluridine