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Influence of SLCO1B1 in gastric cancer patients treated with EOF chemotherapy.

ABSTRACT: Cytochrome-P450 enzymes, ATP-binding cassette transporters, and solute carriers mediate drug metabolism as metabolic enzymes and membrane transporters, respectively. The present study investigated whether single nucleotide polymorphisms (SNPs) in genes encoding these proteins were predictive or prognostic factors in patients with metastatic gastric cancer (MGC) undergoing chemotherapy. A retrospective study of 108 MGC patients who received epirubicin, oxaliplatin, and 5-fluorouracil (EOF) as first-line treatment was performed. A total of 13 SNPs were genotyped, including SLCO1B1 (rs4149056), SLC2A9 (rs16890979, rs6449213, rs734553), ABCG2 (rs2231142), CYP2C9 (rs1057910, rs1799853), CYP2C19 (rs72552267, rs28399504, rs56337013, rs41291556) and CYP1A2 (rs12720461, rs56107638). The associations between these genotypes and disease-control rate (DCR), progression-free survival (PFS) and overall survival (OS) were analyzed. Patients with SLCO1B1 rs4149056 TT genotype had a significantly shorter OS compared with those with a C allele (CC + CT; 312 vs. 565 days, P=0.039). Multivariate analysis revealed that the rs4149056 TT homozygous genotype was an independent prognostic factor for shorter OS (hazard ratio: 2.565, 95% confidence interval: 1.215-5.415, P=0.014). However, no significant associations between SLCO1B1 rs4149056 and PFS were observed, between the other 12 SNPs and PFS or OS, or between any of the 13 SNPs and DCR. In conclusion, SLCO1B1 rs4149056 TT may be an independent predictor of survival in patients with MCG treated with EOF chemotherapy.

SUBMITTER: Feng W

PROVIDER: S-EPMC6126332 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Influence of SLCO1B1 in gastric cancer patients treated with EOF chemotherapy.

Feng Wanjing W Liu Xin X Zhao Xiaoying X Huang Mingzhu M Guo Weijian W Yin Jiliang J Chen Zhiyu Z Zhu Xiaodong X

Oncology letters 20180716 4

Cytochrome-P450 enzymes, ATP-binding cassette transporters, and solute carriers mediate drug metabolism as metabolic enzymes and membrane transporters, respectively. The present study investigated whether single nucleotide polymorphisms (SNPs) in genes encoding these proteins were predictive or prognostic factors in patients with metastatic gastric cancer (MGC) undergoing chemotherapy. A retrospective study of 108 MGC patients who received epirubicin, oxaliplatin, and 5-fluorouracil (EOF) as fir ...[more]

PMID: 30214584

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Project description:Second-line therapy has consistently demonstrated survival benefit if compared with best supportive care; however, there is limited evidence whether further lines of treatment may improve the prognosis of advanced gastric cancer (AGC) patients.Starting from a real-world cohort of 868 AGC patients, we retrospectively analyzed baseline parameters, tumor characteristics, and treatment data of those treated with at least three lines. Categorical features were described through cross-tables and chi-square test. We explored the impact of treatment intensity and progression-free survival (PFS) experienced in previous lines on PFS and overall survival in third-line by uni- and multivariate Cox regression models and described by Kaplan-Meier estimator plot with log-rank test.Overall, 300 patients were included in the analysis. The most common site of primary tumor was gastric body; 45.3% of cancers had an intestinal histotype, 14% were human epidermal growth receptor 2 positive. In third-line, 45.7% of patients received a single-agent chemotherapy, 49.7% a combination regimen. Patients who had experienced a first-line PFS ?6.9 months had a better prognosis compared with those who had achieved a shorter one. Consistently, a second-line PFS ?3.5 months positively influenced the prognosis. Patients receiving a third-line combination regimen had better outcomes compared with those treated with a single-agent chemotherapy.Our real-world study confirms that selected AGC patients may receive third-line treatment. Longer PFS in previous lines or a more intense third-line treatment positively influenced prognosis. Further efforts are warranted to define the best therapeutic sequences, and to identify the optimal candidate for treatment beyond second-line.The benefit of third-line treatment to advanced gastric cancer patients is controversial. This study depicts a real scenario of the clinical practice in Italy, confirming that a non-negligible proportion of patients receive a third-line therapy. Longer progression-free survival in previous treatment lines or higher third-line treatment intensity positively influenced prognosis. Including a large number of real-world patients, this study provides information on third-line treatment from the daily clinical practice; moreover, its results help in defining the best therapeutic sequence and offer some hints to select the optimal candidate for treatment beyond second-line.

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Influence of SLCO1B1 in gastric cancer patients treated with EOF chemotherapy.

Publications

Influence of SLCO1B1 in gastric cancer patients treated with EOF chemotherapy.

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