Research Article: Evaluating dose of cisplatin responsible for causing nephrotoxicity

Date Published: April 25, 2019

Publisher: Public Library of Science

Author(s): Kyouko Higuchi, Takashi Yanagawa, Hideharu Abe.


Nephrotoxicity is a well-known side effect of cisplatin for cancer treatment. Various regimens have been developed to treat cancer based on the type and severity of the tumor. We focus on the docetaxel, cisplatin, and 5-fluorouracil regimen, which is called the TPF regimen, where the standard dose of cisplatin is 60 mg/m2. The aim of this study is to examine the relationship of the dosage of cisplatin that causes nephrotoxicity and back ground factors of patients using information about the dose of cisplatin actually administered to patients. It is shown that nephrotoxicity may be caused by a substantially smaller dosage than the standard dose of cisplatin in the TPF regimen, indicating the need for dose adjustment, taking into account the patient’s background factors in the treatment of a cancer.

Partial Text

Cisplatin is an anticancer agent administered to patients with various types of cancer. Nephrotoxicity is one of the well-known major side effects of cisplatin. The pathophysiological mechanisms of cisplatin nephrotoxicity involve proximal tubular injury, oxidative stress, inflammation, and vascular injury of the kidney. In the proximal tubular injury, several different mechanisms are involved; these include apoptosis, autophagy, dysregulation of cell-cycle proteins, activation of the mitogen-activated protein kinase (MAPK) signaling pathways, direct toxic effects on renal epithelial cells, DNA damage, and mitochondrial dysfunction. It has been reported that 20–30% of patients treated with cisplatin develop nephrotoxicity after 1 to 2 weeks of administration [1–4]. Although various approaches have been developed to prevent cisplatin nephrotoxicity, such as adequate hydration with saline and urinary output by diuretics [5–8], renal damage still occurs.

The negative correlation between pre_scr and log_rate_scr (coefficient, -0.849; p < 0.001) in the predictive model can be explained as follows. The patients in the present study were cancer patients; in particular, 66.7% of them had stage 4 disease. It is known that cancer patients with higher stage have less muscle mass [25–30]. Furthermore, there are several studies that have reported that reduced muscle mass was related to low serum creatinine [31, 32]. Thirty patients (34.5%) had creatinine levels below the lower limit in this study, and there was no patient who exceeded the upper limit of the serum creatinine level; therefore, the negative correlation could be reasonably interpreted as patients with less muscle mass having a higher possibility of developing nephrotoxicity. Note that patients with chronic kidney disease were not included in this study.   Source: