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RENAL ADVERSE EVENTS IN ADVANCED CANCER PATIENTS TREATED WITH TARGETED THERAPY: A RETROSPECTIVE ANALYSIS AND CORRELATION WITH SURVIVAL

Background: The anti-VEGF monoclonal antibody (bevacizumab), the mammalian target of rapamycin (mTOR) inhibitors (everolimus and temsirolimus), and the antiVEGFR tyrosine-kinase inhibitors (anti-VEGF TKIs) represent effective treatment options for several metastatic solid tumors. As described in lit...

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Published in:Anticancer research 2018-04, Vol.38 (4), p.2479
Main Authors: Roberto, Michela, Bassanelli, Maria, Nave, Alessia, Giacinti, Silvana, Poti, Giulia, Fofi, Claudia, Aschelter, Anna Maria, Menè, Paolo, Marchetti, Paolo
Format: Article
Language:English
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Summary:Background: The anti-VEGF monoclonal antibody (bevacizumab), the mammalian target of rapamycin (mTOR) inhibitors (everolimus and temsirolimus), and the antiVEGFR tyrosine-kinase inhibitors (anti-VEGF TKIs) represent effective treatment options for several metastatic solid tumors. As described in literature, these targeted agents may cause renal toxicity. Although renal adverse events are most often mild in severity, may sometimes lead to treatment discontinuation. It is known that VEGF is fundamental to the maintenance of renal function. Therefore, it is possible that using multi-kinase-targeted therapies (TTs) might disorganize normal glomerular function, leading to kidney injuries. However, the most frequently reported manifestations are any grade of both proteinuria and creatinine increase, which may regress after TTs dose adjustment. The exact incidence of renal toxicities and TTs-related mechanism of action are still unknown. A multidisciplinary evaluation with an early nephrological intervention may be useful to manage patients more carefully, prevent treatment discontinuation and to improve survival. Patients and Methods: Patients affected with several advanced stage tumors (6 breast, 22 kidney, 5 colon, 1 neuroendocrine pancreas), treated with targeted therapy and subjected to nephrological evaluation from December 2013 to January 2017 at our Institution, were enrolled in this study. Renal toxicities were graded according to the Common Terminology Criteria for Adverse Events version 4.0. Time to renal failure (TRF) was calculated as the time from starting TTs to the first renal event, defined as a value of creatininaemia ≥001.5 mg/dl and/or proteinuria >1000 mg/24 h. SPSS software v.24, was used for statistical analysis. Results: According to TTs class, in total 34 Patients were grouped as followed: i) 11 (32.4%) anti-VEGF (bevacizumab); ii) 14 (41.2%) VEGF-TKI (sunitinib, sorafenib, pazopanib, axitinib); iii) 9 (26.4%) mTOR inhibitors (temsirolimus, everolimus). With a median followup of 25 months, 23 (67.6%) patients reported a renal event including 14 (60%) of grade 2 (3 proteinuria, 11 hypercreatininaemia) and 6 (26%) of grade 3 (4 proteinuria, 2 hypercreatininaemia) (Figure 1). None grade 4 event or death for toxicity occurred. Twenty-two patients discontinued TTs for toxicity. After 1 month, toxicity regressed in 8 (23.5%) patients which resumed treatment at lower dosage with good tolerability. However, 14 (41.1%) finally stopped TTs for pers
ISSN:0250-7005
1791-7530