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.

Asia Pac J Clin Oncol 2017 Feb 4;13(1):53-60. Epub 2016 Aug 4.

Department of Hematology-Oncolgy, Chonnam National University Medical School, Gwangju, Korea.

Aim: Despite appropriate use of antiemetics including 5-hydroxytryptamine type 3 (5-HT ) 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 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 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 gene should be supported by alternate or additive antiemetics in addition to 5-HT antagonists to control acute emesis.

Download full-text PDF

Source
http://dx.doi.org/10.1111/ajco.12575DOI Listing
February 2017
92 Reads

Publication Analysis

Top Keywords

nausea vomiting
20
day day
12
5-ht receptor
12
abcb1 cyp2d6
12
cyp2d6 htr3b
12
response ramosetron
8
dose escalation
8
chemotherapy-induced nausea
8
variant 5-ht
8
rhodes nausea
8
vomiting retching
8
variants abcb1
8
day
6
nausea
5
vomiting
5
5-ht
5
ramosetron
5
045 rhodes
4
affect response
4
dose 045
4

References

(Supplied by CrossRef)
Use of granisetron transdermal system in the prevention of chemotherapy-induced nausea and vomiting: a review
Tuca et al.
Cancer Manag Res 2010
Chemotherapy induced nausea & vomiting (CINV)
eesh et al.
Int J Basic Clin Pharmacol 2012
The 5-HT3 receptor as a therapeutic target
Thompson et al.
Expert Opin Ther Targets 2007
[A new antiemetic ramosetron hydrochloride]
Tsukagoshi et al.
Gan To Kagaku Ryoho 1997
Management of postoperative nausea and vomiting: focus on palonosetron
Muchatuta et al.
Ther Clin Risk Manag 2009
Nonlinear intestinal absorption of 5-hydroxytryptamine receptor antagonist caused by absorptive and secretory transporters
Tamai et al.
J Pharmacol Exp Ther 1997

Similar Publications