RESUMEN
This study investigates the impact of single nucleotide polymorphisms in genes (SLC22A16 and CBR1) involved in the pharmacokinetics and toxicity of doxorubicin (DOX) in Egyptian female patients with breast cancer.Patients administered DOX (60 mg/m2) for 4 cycles every 3 weeks. The peak DOX plasma concentration was measured using a validated chromatographic method. The genotyping for the selected SNPs, SLC22A16 T > C (rs714368), and CBR1 C > T (rs20572), was performed by RT-PCR. Patients were monitored for hematological and cardiac toxicities.The variant carriers of CBR1 C > T (rs20572) exhibited significantly higher DOX concentration, but no significant association to DOX-induced hematological toxicity. On the other hand, SLC22A16 T > C (rs714368) had no significant influence on DOX plasma concentration, but was significantly correlated with lower risk of neutropenia (OR 0.31, 95% CI 0.12-0.75, p = 0.01) and leukopoenia (OR 0.18, 95% CI 0.07-0.5, p = 0.001). DOX-related cardiotoxicity was correlated with the cumulative dose of DOX (R = 0.238, p = 0.017), but not with any of the two examined SNPs.Genetic polymorphisms in SLC22A16 and CBR1 may explain the inter-individual variations in DOX pharmacokinetics and toxicity. Using pharmacogenetic testing is important to customise drug therapy for cancer patients treated with anthracyclines.
Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Farmacogenética , Egipto , Doxorrubicina/efectos adversos , Polimorfismo de Nucleótido Simple , CardiotoxicidadRESUMEN
OBJECTIVE: This study aimed to compare 12.5 mg empagliflozin effectiveness and safety vs. 50 mg sitagliptin twice daily as an add-on triple medication in Egyptians with type 2 diabetes. PATIENTS AND METHODS: Patients with hemoglobin A1c (HbA1c) between 53 and 86 mmol/mol after receiving open-label either sitagliptin 50 mg (n = 85) or empagliflozin 12.5 mg (n = 85) twice daily for 12 weeks were afterward taken into account for the administration of open-label empagliflozin 12.5 mg (n = 40) and sitagliptin 50 mg (n = 28) respectively twice daily for another 12 weeks of treatment as an added-on triple therapy. Both groups of patients kept taking metformin and empagliflozin 12.5 mg or sitagliptin 50 mg twice daily as prescribed. The HbA1c change from baseline after 12 weeks of triple-added-on therapy was the main endpoint. RESULTS: The sitagliptin group receiving empagliflozin saw a substantial drop in HbA1c, fasting and postprandial plasma glucose levels, body weight, and blood pressure compared to the starting point. As opposed to that, adding sitagliptin to the empagliflozin group non-significantly reduced HbA1c, fasting, and postprandial plasma glucose levels, and systolic blood pressure from baseline but significantly reduced body weight and diastolic blood pressure. Comparing the two groups, adding empagliflozin significantly reduced HbA1c, fasting, and postprandial plasma glucose levels (p < 0.001 for all except fasting plasma glucose level, p = 0.002). While the patient's weight and blood pressure were not significantly affected. CONCLUSIONS: Empagliflozin was superior to sitagliptin in relation to glycemic control, weight, and systolic/diastolic blood pressure reduction.
Asunto(s)
Diabetes Mellitus Tipo 2 , Metformina , Humanos , Glucemia , Peso Corporal , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Egipto , Hemoglobina Glucada , Metformina/uso terapéutico , Fosfato de Sitagliptina/uso terapéuticoRESUMEN
OBJECTIVE: Some studies have shown that metformin inhibits the proliferation of breast cancer (BC) cells via multiple ways. One of these mechanisms is through the indirect control of the IGF-route mediated via the activation of the AMPK-LKB1 pathway in the liver, which leads to a decrease in blood glucose and insulin levels. The objective of this study was to investigate the effects of metformin as adjuvant to chemotherapy on IGF levels in female patients with progressive and non-progressive metastatic BC. PATIENTS AND METHODS: In this trial, 107 women receiving chemotherapy for metastatic breast cancer (MBC) were divided into two groups: the metformin group received 500 mg of metformin twice daily, whereas the control group did not receive any metformin. All patients received chemotherapy according to the South Egypt Cancer Institute's (SECI) established regimen. The level of IGF-1 was determined in the blood at the initiation of therapy (baseline) and at six months post treatment. RESULTS: No substantial differences were noted regarding IGF-1 levels in both groups at baseline (IGF-1 average level was 40.74 ± 36.16 vs. 32.06 ± 20.00 in the metformin and the placebo group, respectively, p = 0.462). While after six months, the mean IGF-1 level was 37.62 ± 31.35 vs. 39.12 ± 2 5.93 in the metformin and placebo groups, respectively, (p = 0.170). CONCLUSIONS: Metformin as an adjuvant to chemotherapy in MBC patients had no significant effect on reducing IGF-l levels which promotes the inhibition of the proliferation of BC cells in MBC patients.