Anti-angiogenic anticancer drugs that block vascular endothelial growth factor (VEGF) can cause kidney damage. An early assessment of the risk of nephrotoxicity would allow the development of optimal treatment approaches and allow for relatively safer therapeutic regimens. The aim of this study was to assess the utility of neutrophilic gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), hypoxia inducible factor-1α (HIF-1α) and nephrin levels in urine as early biomarkers for the nephrotoxicity of anti-VEGF drugs. The study included 50 patients who received anti-VEGF drugs (aflibercept, bevacizumab or ramucirumab) for 8 weeks. The levels of KIM-1, NGAL, HIF-1α and nephrin in urine samples were determined by ELISA before treatment and after 1, 2, 4 and 8 weeks of treatment. To assess risk factors for nephrotoxicity, a logistic regression analysis was performed with the inclusion of the primary clinical and laboratory parameters. The primary outcome measure was a decrease in glomerular filtration rate (GFR) to <60 ml/min/1.73 m 2 at 8 weeks, and nephrotoxicity resulting in discontinuation within 9 months. The primary outcome goal was achieved in 21 (42%) patients treated with anti-VEGF drugs. Increased NGAL, KIM-1, HIF-1α and nephrin levels in urine at 1 week of treatment predicted the development of nephrotoxicity. High sensitivity and specificity of these urinary biomarkers were established by ROC analysis: KIM-1 [area under the curve (AUC) 0.69], NGAL (AUC 0.7), HIF-1α (AUC 0.7) and nephrin (AUC 0.7). The unfavorable predictors of nephrotoxicity were an initial decrease in estimated GFR, a history of arterial hypertension, and an increase in urinary concentration KIM-1 OR of 1.1 [CI 95% 1.02-1.183], and HIF-1α OR of 5.6 [CI 95% 3.601-8.949] (P<0,05) at 1 and 2 weeks of treatment. Urinary NGAL, KIM-1, HIF-1α and nephrin are early biomarkers of nephrotoxicity following treatment with anti-VEGF anticancer drugs. The independent risk factors for nephrotoxicity are the initial decrease in GFR, arterial hypertension, and an increase in the concentration of KIM-1 and HIF-1α in the urine in the early stages of therapy.
The only option of systemic therapy for triple-negative breast cancer (TNBC) was cytotoxic chemotherapy until recently, moreover the unitary standard of care for metastatic forms was not strictly defined. That is why paradigm of the treatment remains at the discretion of the doctor and it is empirical, consisting of precise combination of drugs. TNBC is infamous as the worst prognostic subtype. The absence of estrogen and progesterone receptors expression and HER2 amplification in this subtype of tumors made the usage of target therapy impossible, which is essential for successful treatment of luminal and HER2 positive breast cancer subtypes. The data about potential immunogenicity of tumor in TNBC launched the investigation of immunotherapy efficacy in this subtype of breast cancer. International clinical trial Impassion130 has not only created the basis in this field of TNBC treatment but also identified and determined the “benefiters”-cohort of patients concerning one of the most important goals - improving overall survival, that is so significant for patients with this subtype of breast cancer.
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