Relationship Analysis of CYP3A4*18 Gene Polymorphism with Therapeutic Efficacy and ADR of EGFR-TKI in Advanced NSCLC Patients Receiving Primary Treatment / 中国药房
China Pharmacy
; (12): 4465-4470, 2017.
Article
Dans Zh
| WPRIM
| ID: wpr-704437
Responsable en Bibliothèque :
WPRO
ABSTRACT
OBJECTIVE:
To investigate the relationship of Cytochrome P450 (CYP)3A4* 18 gene polymorphism with therapeutic efficacy and ADR of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) patients receiving primary treatment.METHODS:
A total of 46 advanced NSCLC patients receiving primary EGFR-TKI (gefitinib or edotinib) treatment until disease progression or intolerance were selected from our hospital during Jan.2013-Mar.2016,and (gefitinib of erlotinib) treatment until disease progression or intolerance.CYP3A4*18 genotype was detected by PCR and direct sequencing.Clinical efficacies,progression-free survival (PFS) and the occurrence of ADR were compared among differ ent genotypes.RESULTS:
Among 46 patients,there were 17 cases of CYP3A4*18 wild-type and 29 cases of CYP3A4*18 mutation-type,with mutation frequency of 63.0%.The objective response rate (ORR) of CYP3A4*18 wild-type patients was 23.5%,and disease control rate (DCR) of them was 70.6%.For CYP3A4*18 mutation-type patients,ORR and DCR were 27.6% and 69.0%.There was no statistical significance in the proportion of patients with partial response,stable disease or progressive dis ease,ORR or DCR among different genotypes (P>0.05).PFS of female patients were significantly longer than male patients;those of patients without smoking history were significantly longer than those with smoking history,with statistical significance (P<0.05).There was no correlation between patients' age,therapy drugs,Eastern Oncology Collaboration scores,EGFR mutation types,CYP3A4*18 genotypes and PFS (P>0.05).Patients'gender and smoking history were independent prognostic factors for PFS [odds ratios were 3.438,0.205,95% CI were(1.393,8.488),(0.088,0.481)].Among CYP3A4* 18 wild-type patients,6 patients suffered from rash (35.3%) and 3 diarrhea (17.6%).Among mutation-type patients,26 patients suffered from rash (89.7%) and 15 diarrhea (51.7%),with statistical significance (P<0.05).There was no statistical significance in the incidence of liver function injury and interstitial dermatitis among different genotypes (P>0.05).CONCLUSIONS:
CYP3A4*18 gene polymorphism may be not associated with therapeutic efficacy of EGFR-TKI in advanced NSCLC patients receiving primary treatment,but it is correlated with the occurrence of ADR.Mutation type patients are more likely to suffered from rash,diarrhea and other ADR.
Texte intégral:
1
Indice:
WPRIM
Type d'étude:
Prognostic_studies
langue:
Zh
Texte intégral:
China Pharmacy
Année:
2017
Type:
Article