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1.
Eur J Gynaecol Oncol ; 38(3): 335-341, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29693868

RESUMEN

A review of literature data related to the effects of overweight and obesity on the development and course of selected gynecological malignancies: endometrial, breast and ovarian cancer is presented. Three hypotheses are included in an attempt to explain this rela- tionship: the adipokinine hypothesis, a hypothesis involving the effects of excessive estrogen levels, and the insulin hypothesis.


Asunto(s)
Neoplasias de los Genitales Femeninos/etiología , Obesidad/complicaciones , Sobrepeso/complicaciones , Adipoquinas/sangre , Neoplasias de la Mama/etiología , Neoplasias Endometriales/etiología , Estrógenos/sangre , Femenino , Humanos , Insulina/fisiología , Neoplasias Ováricas/etiología
2.
Eur Rev Med Pharmacol Sci ; 26(24): 9426-9436, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36591851

RESUMEN

OBJECTIVE: Olaparib is the poly-[Adenosine diphosphate ribose (ADP-ribose)] polymerase inhibitor (PARPI) used in maintenance therapy of patients with platinum-sensitive ovarian cancer with mutations in breast cancer genes 1/2 (BRCA1/2). Oncologists still do not have recommendations of treatment depending on efficient plasma concentrations of the PARP inhibitor. The aim of the study was the assessment of plasma trough concentrations of olaparib at steady state (Ctrough) in ovarian cancer patients. The severity of olaparib adverse effects (AEs) was noted. PATIENTS AND METHODS: The retrospective study involved 33 patients [mean standard deviation (SD)]; age 57.0 (8.4) years; weight 68.7 (13.7) kg; and body mass index (BMI) 26.4 (4.9) kg/m2, with ovarian cancer treated with olaparib (tablets in dose 300 mg/12 h, 250 mg/12 h, 200 mg/12 h or capsules 400 mg/12 h, 200 mg/12 h, 100 mg/12 h). Plasma drug levels were measured by HPLC-UV method (λ = 254 nm; Symmetry C8 column; gradient flow). The severity of olaparib AEs was assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 scale. Drug interactions were analyzed. RESULTS: In total, 130 measurements (n) of Ctrough were determined in 33 patients (median sample frequency per patient was 4). The olaparib Ctrough in patients with AEs was 87.840-7,213.262 ng/mL [coefficient of variation (CV) = 91%], in patients without AEs 48.021-7,073.350 ng/mL (CV = 88%). AEs were the following: fatigue (modest, n = 4, severe, n = 2), anemia (grade G1 n = 66, G2 n = 6, G3 n = 3), neutropenia (grade G1 n = 15, G2 n = 4), prediabetes (n = 1). There was a correlation between Ctrough and olaparib-induced fatigue (p = 0.0015). The lower values of dose-adjusted olaparib concentrations (p = 0.0121) and dose/kg-adjusted olaparib concentrations (p = 0.0389) were correlated with higher grade of neutropenia. CONCLUSIONS: There was a correlation between Ctrough, expressed as ng/ml, ng/ml/mg or ng/ml/mg/kg, and fatigue degree, but not anemia. Patients with neutropenia had statistically significant lower plasma concentrations of olaparib.


Asunto(s)
Neutropenia , Neoplasias Ováricas , Humanos , Femenino , Persona de Mediana Edad , Monitoreo de Drogas , Estudios Retrospectivos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Ftalazinas/efectos adversos , Fatiga , Neutropenia/inducido químicamente , Neutropenia/tratamiento farmacológico
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