Chinese Clinical Oncology

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Trial of the correlation between cytochrome oxidase CYP3A4 with the susceptibility of paclitaxel-based regimen for advanced gastric cancer

YANG Jianwei,CHEN Zeng,SU Ying,GAO Wei,LIN Jinyuan,JIA Jing,LIN Huamei,MENG Yan   

  1. Department of Medical Oncology, Fujian Provincial Cancer Hospital, Fuzhou 350014,China
  • Received:2013-08-23 Revised:2013-12-08 Online:2014-01-31 Published:2014-01-31

Abstract: bjective To inveatigate the relationship between susceptibility of paclitaxelbased regimen and gene polymorphisms of cytochrome oxidase CYP3A4 for advanced gastric cancer. Methods Peripheral venous blood samples of 53 advanced gastric cancer patients were enrolled to test the mutation of CYP3A4 gene by denaturing high performance liquid chromatography(DHPLC)and DNA sequencing. The relation between the efficacy of paclitaxel-based regimen and CYP3A4 gene polymorphisms was further analyzed. Results DHPLC indicated that among the 53 patients,21 cases showed bimodal type(mutation)and 32 cases were of unimodal type(wild-type). Sequencing results showed that the deletion mutation was found at the 27th basic group of C in exon 10 of CYP3A4 gene. The response rate(RR) and disease control rate(DCR)of wildtype group were 40.6% and 84.4%,while in mutation group they were 33.3% and 85.7%,with no significance between the two groups(P>0.05). The median progressionfree survival(PFS)was 6.5 months(95%CI:3.576-9.424 months),and the median overall survival(OS)was 11.0 months(95%CI:6.955-15.045 months)of the 53 patients. The median PFS and OS in wild-type group had no differences compared with those in mutation group(7.0 months vs.7.0 months,P>0.05;10.0 months vs.14.0 months,P>0.05). Between wild-type and mutation groups,the median PFS of patients applied with oxaliplatin containing regimen and the median OS in patients applied with/without oxaliplatin had no significant differences(P>0.05),while the median PFS in patients received non-oxaliplatin regimen had statistical differences(P=0.024). The median PFS and OS in patients reveiving 3-drug or 2-drug regimen had no correlation with CYP3A4 gene polymorphisms. The adverse effect in the two groups were mild,mainly in grade 1-2. The common adverse effects were anorexia,nausea/vomiting and leukopenia. Conclusion Deletion mutation was located in the 27th basic group of C in exon 10 of CYP3A4 gene. Paclitaxel-based regimen has a trend to prolong the OS of advanced gastric cancer with mutation type.

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