Association of ABCB1 polymorphisms with the antiemetic efficacy of granisetron plus dexamethasone in breast cancer patients.
Resistance to antiemetic treatment with 5-hydroxytryptamine 3 receptor antagonists is a problem, with 20-30% of patients showing unsatisfactory responses. Efflux transport by P-glycoprotein, encoded by the ATP-binding cassette ABCB1 gene in the blood-brain barrier, has been the suggested resistance mechanism. We evaluated the association between the antiemetic efficacy of granisetron plus dexamethasone and ABCB1 polymorphisms 3435C>T and 2677G>T/A. Sixty-four breast cancer patients treated with doxorubicin plus cyclophosphamide were evaluated for their responses to antiemetic therapy. Genotyping of patient DNA samples for ABCB1 single nucleotide polymorphisms was performed; the genotypes were then investigated for their association with the efficacy of prophylactic antiemetics. The acute phase complete response rate was 83% in GG subjects (n = 12), and 69% (n = 35) and 41% (n = 17) in heterozygous and homozygous carriers of the 2677T/A allele, respectively (p = 0.047). The ABCB1 2677 TT genotype group showed significantly lower rates of complete control of acute emesis than the group with GG genotypes (p = 0.045). No significant association with complete response was found for 3435C>T (p = 0.190). ABCB1 polymorphisms may influence the extent of acute emesis control in granisetron-treated patients, making the ABCB1 genotype a predictor of prophylactic antiemetic response.
Department of Clinical Pharmacology and Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Japan. d-tsuji@u-shizuoka-ken.ac.jp
Daiki
D
Tsuji
Yong-Il
YI
Kim
Hidenori
H
Nakamichi
Takashi
T
Daimon
Kaori
K
Suwa
Yutaro
Y
Iwabe
Hideki
H
Hayashi
Kazuyuki
K
Inoue
Masayuki
M
Yoshida
Kunihiko
K
Itoh
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000502:physiology; D000932:Antiemetics / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms / Q000188:drug therapy*; D003520:Cyclophosphamide; D003907:Dexamethasone / Q000008:administration & dosage*; D004317:Doxorubicin; D005260:Female; D017829:Granisetron / Q000008:administration & dosage*; D006801:Humans; D020641:Polymorphism, Single Nucleotide
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000932:Antiemetics; D003520:Cyclophosphamide; D003907:Dexamethasone; D004317:Doxorubicin; D017829:Granisetron; C513055:ABCB1 protein, human