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Int J Mol Sci ; 22(3)2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33513824

RESUMO

Cisplatin is one of the most widely used chemotherapeutic agents in oncology, although its nephrotoxicity limits application and dosage. We present the results of a clinical study on prophylaxis of cisplatin-induced nephrotoxicity in patients with peritoneal carcinomatosis undergoing cytoreduction and hyperthermic intraperitoneal intraoperative chemotherapy (HIPEC-cisplatin). Prophylaxis was with imipenem/cilastatin. Cilastatin is a selective inhibitor of renal dehydropeptidase I in the proximal renal tubule cells that can reduce the nephrotoxicity of cisplatin. Unfortunately, cilastatin is not currently marketed alone, and can only be administered in combination with imipenem. The study has a retrospective part that serves as a control (n = 99 patients receiving standard surgical prophylaxis) and a prospective part with imipenem/cilastatin prophylaxis corresponding to the study group (n = 85 patients). In both groups, we collected specific data on preoperative risk factors of renal damage, fluid management, hemodynamic control, and urine volume during surgery (including the hyperthermic chemotherapy perfusion), as well as data on hemodynamic and renal function during the first seven days after surgery. The main finding of the study is that cilastatin may exert a nephroprotective effect in patients with peritoneal carcinomatosis undergoing cytoreduction and hyperthermic intraperitoneal cisplatin perfusion. Creatinine values remained lower than in the control group (ANOVA test, p = 0.037). This translates into easier management of these patients in the postoperative period, with significantly shorter intensive care unit (ICU) and hospital stay.


Assuntos
Antineoplásicos/uso terapêutico , Cilastatina/farmacologia , Cisplatino/efeitos adversos , Terapia Combinada/métodos , Quimioterapia Intraperitoneal Hipertérmica/efeitos adversos , Rim/efeitos dos fármacos , Neoplasias Peritoneais/tratamento farmacológico , Insuficiência Renal/prevenção & controle , Adulto , Idoso , Cilastatina/uso terapêutico , Creatinina/sangue , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica/métodos , Imipenem/farmacologia , Imipenem/uso terapêutico , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/complicações , Neoplasias Peritoneais/mortalidade , Estudos Prospectivos , Insuficiência Renal/complicações , Insuficiência Renal/etiologia , Estudos Retrospectivos
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