Homozygous CDA*3 is a major cause of life-threatening toxicities in gemcitabine-treated Japanese cancer patients.
Among 242 Japanese pancreatic cancer patients, three patients (1.2%) encountered life-threatening toxicities, including myelosuppression, after gemcitabine-based chemotherapies. Two of them carried homozygous CDA*3 (CDA208G>A [Ala70Thr]), and showed extremely low plasma cytidine deaminase activity and gemcitabine clearance. Our results suggest that homozygous *3 is a major factor causing gemcitabine-mediated severe adverse reactions among the Japanese population.
Ueno
H
H
Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. hiueno@ncc.go.jp
Kaniwa
N
N
Okusaka
T
T
Ikeda
M
M
Morizane
C
C
Kondo
S
S
Sugiyama
E
E
Kim
S R
SR
Hasegawa
R
R
Saito
Y
Y
Yoshida
T
T
Saijo
N
N
Sawada
J
J
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects*; D019540:Area Under Curve; D044466:Asian People / Q000235:genetics*; D003564:Cytidine Deaminase / Q000235:genetics*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D020641:Polymorphism, Single Nucleotide; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D003564:Cytidine Deaminase; D000093542:Gemcitabine