Cisplatin-induced nephrotoxicity in children: what is the best protective strategy?

Abstract

Introduction Platinum compounds, which are considerably effective for the treatment of childhood malignancies, have significantly contributed to the increase in long-term survival of children with cancer. Unfortunately, children receiving cisplatin-based chemotherapy have been known to be at risk for severe disabling adverse effects, such as nephrotoxicity. Methods A literature research of the MEDLINE PubMed database was conducted to identify articles published between 1980 and 2019 reviewing “Cisplatin AND mannitol.” Results The primary pharmacodynamics and clinical characteristics of cisplatin were described, focusing on its renal toxic effects and potential preventive strategies, in order to improve clinical outcomes among children with cancer aged 1 to 14 years. Currently, selecting either hydration alone or hydration plus mannitol for preventing nephrotoxicity has been controversial considering the lack of guidelines to provide treatment recommendations both among adults and children. Conclusions Appropriate knowledge regarding the pharmacokinetics and toxicological profile of cisplatin may help physicians prevent renal toxicity. Unfortunately, published data regarding the nephroprotective utility of adding mannitol appear to be inconclusive. As such, appropriate hydration remains the main fundamental strategy for reducing the risk of cisplatin-induced nephrotoxicity. Considering the increasing number of children safely cured of their tumours, it is imperative that those treated with cisplatin receive the most appropriate nephroprotective strategy for reducing the negative impact of platinum compounds on quality of life.

Feasibility of dose‐dense cisplatin‐based chemotherapy in Japanese children with high‐risk hepatoblastoma: Analysis of the JPLT3‐H pilot study

“…These results recall the importance of aggressive hydration with magnesium supplementation to prevent renal toxicity with administration of cisplatin. [14][15][16] Ototoxicity is one of the most common and problematic adverse effects of cisplatin, as it can lead to permanent hearing loss and impairment of neurocognitive function and quality of life. 17,18 While half of the patients had moderate to severe ototoxicity in the SIOPEL-4 study, 9 three out of eight (38%) who completed the treatment did so in our study.…”

Transplacental Passage and Fetal Effects of Antineoplastic Treatment during Pregnancy

“…Only one baby with cerebral ventriculomegaly and cerebral atrophy is described after intrauterine exposure to cisplatin (with bleomycin and etoposide) for maternal ovarian cancer during the second and third trimesters of pregnancy, but its etiology is not clear [16]. In a systematic review of 43 cases of pregnant women treated with platinum compounds, among 36 patients who received cisplatin, two fetal malformations occurred (microphthalmos and ventriculomegaly), but the role of cisplatin is not clear, because of the short period between malformation time and cisplatin administration [90,91].…”

Cisplatin toxicity is mediated by direct binding to TLR4 through a mechanism that is distinct from metal allergens

“…The development of CITs, including, but not limited to, nephrotoxicity, peripheral neurotoxicity, and ototoxicity, appears to be dependent on both the dosages administered and the age of patients. Children appear the most susceptible, particularly to cisplatin-induced hearing loss (Kamalakar et al , 1977; Romano et al , 2020; Ruggiero et al , 2021). Second- and third-generation platinum-based drugs, such as carboplatin and oxaliplatin, were explicitly designed with the intention of reducing those toxicities and overcoming chemotherapy resistance (Kelland, 2007).…”