Correlation between gene polymorphisms of CYP3A4 and multi line chemotherapy, cycles of chemotherapy or adverse reactions in gastric cancer patients received therapy of paclitaxel and/or oxaliplatin combination regimens
YANG Jianwei;SU Ying;CHEN Zeng;MENG Yan;GAO Wei;LIN Jinyuan;Department of Medical Oncology, Fujian Province Cancer Hospital;
Objective: To investigate correlation between gene polymorphisms of drug metabolizing enzyme CYP3A4 and multi line chemotherapy, cycles of chemotherapy, or adverse reactions in gastric cancer patients received therapy of paclitaxel and/or oxaliplatin combination regimens. Methods: Patients with advanced gastric cancer who received palliative chemotherapy of paclitaxel and/or oxaliplatin combination regimens were from Fujian Province Tumor Hospital. Peripheral venous blood was collected before the chemotherapy. DNA was extracted and amplified by PCR. Denaturing high performance liquid chromatography(DHPLC) technology was performed to detect gene polymorphisms. The multi line chemotherapy, cycles of chemotherapy, and adverse reactions in patients with dif erent CYP3A4 gene polymorphisms were evaluated. Results: The genotype of CYP3A4 in 53 patients was screened by DHPLC, of which 21 cases were bimodal(mutation) and 32 were unimodal(wild type). Sequencing results showed that in the bimodal CYP3A4, the 27th basic group of C in Exon 10 of the CYP3A4 gene was the absence of mutation. In the unimodal CYP3A4 group, 15 cases received first line therapy, 10 received second line therapy, 8 received therapy beyond second line drug, and 3 received therapy beyond third line drugs. The average chemotherapy cycle was 8.2 and the median overall survival was 13.0 months(95% CI: 7.092 18.908 months). In the bimodal CYP3A4 group, 10 cases received first line therapy, 8 received second line therapy, and 3 received therapy beyond second line drug. The average chemotherapy cycle was 8.7 and the median overall survival was 14.0 months(95% CI: 7.555 20.445 months). There was no statistical difference in the median overall survival between the unimodal CYP3A4 group and the bimodal CYP3A4 group(P=0.326). For the adverse reactions, wild type displayed lower incidence than the mutant type, especially at the 3 4 grade side ef ects, including nausea, vomiting, fatigue, leukopenia, drug induced hepatitis, etc. Conclusion: The 27th basic group of C in Exon 10 of the CYP3A4 gene is missing. The CYP3A4 gene polymorphism is associated with adverse reactions of chemotherapy, but it can not be used as a predictor for ei cacy of chemotherapy.
【Fund】： 福建省自然科学基金(2009J01120);; 福建省医学创新项目(2009 CXB 27)~~
【CateGory Index】： R735.2
【CateGory Index】： R735.2