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Effect of the allelic variants of ABCB1, CYP2D6 and HTR3B on response of ramosetron to prevent chemotherapy‐induced nausea and vomiting in Korean cancer patients
Author(s) -
Kang Gaeun,
Kim KaRham,
Shim HyunJeong,
Hwang JunEul,
Bae WooKyun,
Chung IkJoo,
Kim HeeNam,
Lee Jongtae,
Choi Kyungmee,
Shin HeeYoung,
Kim JongKeun,
Jeong SeongWook,
Cho SangHee
Publication year - 2017
Publication title -
asia‐pacific journal of clinical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 29
eISSN - 1743-7563
pISSN - 1743-7555
DOI - 10.1111/ajco.12575
Subject(s) - retching , chemotherapy induced nausea and vomiting , nausea , vomiting , palonosetron , medicine , antiemetic , chemotherapy , anesthesia , pharmacology , aprepitant , gastroenterology , oncology
Aim Despite appropriate use of antiemetics including 5‐hydroxytryptamine type 3 (5‐HT 3 ) receptor antagonists, chemotherapy‐induced nausea and vomiting (CINV) is still an unsolved problem in patients with anticancer drugs. We examined whether the variants of ABCB1, CYP2D6 and HTR3B affect efficacy of ramosetron, a selective 5‐HT 3 receptor antagonist in a dose escalation clinical trial. Methods We conducted a clinical trial on patients who underwent FOLFOX combination chemotherapy. The participants were randomized into three groups of ramosetron: 0.3 mg (standard dose), 0.45 mg and 0.6 mg. Rhodes index of nausea, vomiting and retching were measured at 1, 6 h, day 1, day 2 and day 7 after the administration of ramosetron as a clinical parameter of CINV and polymorphism was analyzed from genomic DNA. Results There was a dose‐dependent decrease in the nausea and vomiting scores at day 1 and day 2, not statistically significant. The Rhodes index of nausea, vomiting and retching score at day 1 in participants with HTR3B ‐100_‐102delAAG deletion variants was significantly higher than wild type participants, regardless of dosages. However, the polymorphisms including ABCB1 , CYP2D6 and other HTR3B genes did not affect response to ramosetron after chemotherapy. Conclusion These results suggest that the ‐AAG deletion variant of the 5‐HT 3B receptor gene may contribute to variability in response to antiemetic therapy for CINV regardless of dose escalation. These results suggest that carrying a ‐100_‐102delAAG variant of 5‐HT 3 gene should be supported by alternate or additive antiemetics in addition to 5‐HT 3 antagonists to control acute emesis.