Search

Background: This study aimed to determine whether single nucleotide polymorphisms (SNPs) in genes involved in DNA repair or metabolism of taxanes or platinum could predict toxicity or response to first-line chemotherapy in ovarian cancer. Methods: Twenty-six selected SNPs in 18 genes were genotyped in 322 patients treated with first-line paclitaxel-carboplatin or carboplatin mono-therapy. Genotypes were correlated with toxicity events (anemia, neutropenia, thrombocytopenia, febrile neutropenia, neurotoxicity), use of growth factors and survival. Results: The risk of anemia was increased for variant alleles of rs1128503 (ABCB1, C > T; p = 0.023, OR = 1.71, 95% CI = 1.07-2.71), rs363717 (ABCA1, A > G; p = 0.002, OR = 2.08, 95% CI = 1.32-3.27) and rs11615 (ERCC1, T > C; p = 0.031, OR = 1.61, 95% CI = 1.04-2.50), while it was decreased for variant alleles of rs12762549 (ABCC2, C > G; p = 0.004, OR = 0.51, 95% CI = 0.33-0.81). Likewise, increased risk of thrombocytopenia was associated with rs4986910 (CYP3A4, T > C; p = 0.025, OR = 4.99, 95% CI = 1.22-20.31). No significant correlations were found for neurotoxicity. Variant alleles of rs2073337 (ABCC2, A > G; p = 0.039, OR = 0.60, 95% CI = 0.37-0.98), rs1695 (ABCC1, A > G; p = 0.017, OR = 0.55, 95% CI 0.33-0.90) and rs1799793 (ERCC2, G > A; p = 0.042, OR = 0.63, 95% CI 0.41-0.98) associated with the use of colony stimulating factors (CSF), while rs2074087 (ABCC1, G > C; p = 0.011, OR = 2.09, 95% CI 1.18-3.68) correlated with use of erythropoiesis stimulating agents (ESAs). Homozygous carriers of the rs1799793 (ERCC2, G > A) G-allele had a prolonged platinum-free interval (p = 0.016). Conclusions: Our data reveal significant correlations between genetic variants of transport, hepatic metabolism, platinum related detoxification or DNA damage repair and toxicity or outcome in ovarian cancer. [ABSTRACT FROM AUTHOR]

Background: Several observational studies on hypertensive patients have shown a gap between therapeutic targets recommended in guidelines and those achieved in daily practice. The ESCAPE trial aimed to determine whether a multifaceted intervention focused on general practitioners (GPs), could increase significantly the proportion of hypertensive patients at high risk in primary prevention who achieved all their recommended therapeutic targets. Methods: A pragmatic, cluster randomized trial involving 257 GPs randomized by region. The GPs in the intervention group had a one-day training session and were given an electronic blood pressure measurement device and a short recommendation leaflet. Along with usual follow-up, they focused one consultation on hypertension and other cardiovascular risk factors every six months for two years. They also received feedback at baseline and at one year on their patients' clinical and biological parameters. Main outcome measures were change in the proportion of patients achieving all their therapeutic targets and each individual therapeutic target at two years, and quality of life. Results: 1,832 high-risk hypertensive patients were included. After two years, the proportion of patients achieving all their therapeutic targets increased significantly in both groups, but significantly more in the intervention group: OR (odds-ratio) 1.89, (95% confidence interval (CI) 1.09 to 3.27, P = 0.02). Significantly more patients achieved their blood pressure targets in the intervention group than in the usual care group: OR 2.03 (95% CI 1.44 to 2.88, P < 0.0001). Systolic and diastolic blood pressures decreased significantly more in the intervention group than in the usual care group, by 4.8 mmHg and 1.9 mmHg, respectively (P < 0.0001 for both). There were no significant difference changes in physical and mental quality of life between groups. Conclusion: An easy-to-perform, multifaceted intervention targeting only GPs increased significantly the proportion of high-risk hypertensive patients in primary prevention achieving their recommended therapeutic targets. [ABSTRACT FROM AUTHOR]