Objective: The aim of the study was to investigate the relationship between susceptibility of paclitaxel-based regimen and gene polymorphisms of cytochrome oxidase CYP3A4 for advanced gastric cancer. Methods: Peripher...Objective: The aim of the study was to investigate the relationship between susceptibility of paclitaxel-based regimen and gene polymorphisms of cytochrome oxidase CYP3A4 for advanced gastric cancer. Methods: Peripheral venous blood sample 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 biomodal type(mutation) and 32 cases were of unimodal type(wild-type). Sequencing results showed that the deletion mutation was found at the 27 th 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%, respectively, with no significances between the two groups(P > 0.05). Of all 53 cases, 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). 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 regime had statistical differences(P = 0.024). The median PFS and OS in patients receiving 3-drug or 2-drug regimes had no correlation with CYP3A4 gene polymorphisms. The adverse effects in the two groups were mild, mainly in grades 1–2. The common adverse effects were anorexia, nausea/vomiting and leucopenia. Conclusion: Deletion mutation was located in the 27 th basic group of C in exon 10 of CYP3A4 gene. Paclitaxel-based regime has a trend to prolong the OS of advanced gastric cancer with mutation type.展开更多
基金Supported by grants from the National Natural Science Foundation of Fujian Province(No.2009J01120)Innovation in Medical Foundation of Fujian Province(No.2009-CXB-27)
文摘Objective: The aim of the study was to investigate the relationship between susceptibility of paclitaxel-based regimen and gene polymorphisms of cytochrome oxidase CYP3A4 for advanced gastric cancer. Methods: Peripheral venous blood sample 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 biomodal type(mutation) and 32 cases were of unimodal type(wild-type). Sequencing results showed that the deletion mutation was found at the 27 th 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%, respectively, with no significances between the two groups(P > 0.05). Of all 53 cases, 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). 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 regime had statistical differences(P = 0.024). The median PFS and OS in patients receiving 3-drug or 2-drug regimes had no correlation with CYP3A4 gene polymorphisms. The adverse effects in the two groups were mild, mainly in grades 1–2. The common adverse effects were anorexia, nausea/vomiting and leucopenia. Conclusion: Deletion mutation was located in the 27 th basic group of C in exon 10 of CYP3A4 gene. Paclitaxel-based regime has a trend to prolong the OS of advanced gastric cancer with mutation type.
