FP096TYROSINE KINASE İNHIBITORS AND RENAL EFFECTS

Abstract

INTRODUCTION: Epidermal growth factor receptor (EGFR) is a transmembrane receptor with a cytoplasmic tyrosine kinase (TK) domain present on many solid tumors including non-small cell lung cancer (NSCLC). Targeting the EGFR include two monoclonal antibodies, cetuximab and panitumumab, and three orally active small-molecule inhibitors of the tyrosine kinase (TKI) domain, erlotinib, gefitinib, and afatinib. Since these therapies are recently used in cancer treatment, the incidence, severity, and pattern of renal toxicities may vary and not exactly known. In this study we aimed to evaluate the TKIs related renal problems in EGFR mutation-positive metastatic NSCLC patients used as a first-line regimen. METHODS: 47 patients with EGFR mutation-positive metastatic NSCLC were prospectively followed after the TKI treatment for 3 months. 1 patient was excluded because TKI was stopped early. 5 patients were excluded because of uncontrolled Diabetes Mellitus (DM). All patients were evaluated for their standard clinical and biochemical parameters at the beginning of treatment and after 3 months. Urine samples are collected over a 24-hour period to estimate microalbuminuria and proteinuria. RESULTS: Study population was consisted of 41 patients; 26 (63%) females and 15 (37%) males with mean age of 67.15±11.91. Erlotinib was started on 25 (61%) patients, afatinib was started on 11 (26%) patients and gefitinib was started on 5 (13%) patients according to their oncologic evaluation with Medical Oncology. None of patients were with DM. One patient had stable coronary heart disease without any clinical symptom. Patients were analyzed according to having hypertension (HT) or not. 25 (61%) patients were on antihypertensive treatment. Patients were followed with self-monitoring blood pressure (BP) measurements at home. To confirm BPs were at target level (<130/80 mmHg) we used both morning and evening BP taken over one week at the beginning and during monthly follow up. We analysed the data at the beginning and at the 3rd month of TKI treatment. Estimated glomerular filtration rate (e-GFR) of patients were>60 mL/min/1.73m2. None of the patients had acute kidney injury during and after 3rd month of treatment. There was no serum electrolyte abnormality (Blood Na, K, Ca levels) during the follow up period and at the end of 3rd month. In respect to 24-hour urine analysis none of patients had proteinuria at the beginning. But when we grouped patients due to HT existence, 24-hr microalbuminuria was high in HT group at the end of 3rd month (54.8mgr/day vs 38.8mgr/day, p=0.027). CONCLUSIONS: Anti-target therapies are recently used agents that improve patient survival in cancer patients. But unknown renal side-effects may alter the use of these regimens. Our study is a prospective study in this field. Altough our follow-up period is short, this study shows in long durations the agents may affect kidney. As nephrologists, we should be alert about the coming problems and be careful especially about the patients with comorbid conditions like HT.