Retrospective Analysis of Cisplatin Nephrotoxicity in Patients With Head and Neck Cancer Receiving Outpatient Treatment With Concurrent High-dose Cisplatin and Radiotherapy

Abstract

Objectives Cisplatin remains the pivotal chemotherapy in squamous cell carcinoma of the head and neck (SCCHN), with nephrotoxicity considered the dose-limiting toxicity. The purpose of our study was to propose an outpatient high-dose cisplatin (op-HD-cis) protocol aimed at preventing nephrotoxicity and to analyze the results of its utilization in patients with SCCHN treated with concurrent radiotherapy. Methods We retrospectively evaluated 82 SCCHN patients treated with op-HD-cis concurrent with radiotherapy at our institution. Acute kidney injury (AKI) and chronic kidney disease (CKD) were defined by Kidney Disease Improving Global Outcomes criteria. Associated factors were identified using analysis of covariance models for categorical variables and adjusted Pearson correlations for continuous variables. Results The incidence of AKI during treatment was 34.2%. With a median follow-up of 25.7 months, the average decrease in eGFR was 12.57 ml/min/1.73m2 (SD = 18.58). At 1-year and at last follow-up, 5.4% and 4.4% of patients had eGFR <60 ml/min/1.73m2, respectively. Predictors associated with AKI and CKD were: lower baseline weight and creatinine, higher baseline creatinine clearance, smoking, female gender, African American race, hypertension, and increased hydration and magnesium replacement requirements. Conclusions We encountered limited early and late nephrotoxicity. Importantly, nephrotoxicity was not the main dose-limiting toxicity. Our results emphasize the importance of close monitoring and additional replacement of water and electrolytes as needed. A consistent method of measuring and reporting chemotherapy-induced nephrotoxicity would be a valuable contribution to the literature.

The Predictive Role of the Biomarker Kidney Molecule-1 (KIM-1) in Acute Kidney Injury (AKI) Cisplatin-Induced Nephrotoxicity

“…Its soluble form is a 90 kDa molecule (as compared to the membrane bound 104 kDa form) found in the urine of both animals and humans with renal injury. Its presence was associated with AKI in several experimental studies [34,41,42,43,44,45,46,47,48,49,50] and some authors suggest that it may be predictive of cisplatin nephrotoxicity [119,120,121,122,123,124,125,126,127,128,129,130,131,132,133,134,135]. Anti-KIM-1 antibodies have been developed as a potential therapy in neoplasia characterized by KIM-1 overexpression (renal, ovarian, and lung carcinomas) [167,168].…”

“…KIM-1 levels increased after one-day post-cisplatin administration and this elevation correlated with AKI. Moreover, a form of kidney injury was reported in more than one quarter of patients after the first dose of cisplatin [122,123]. Authors concluded that this biomarker may be able to predict cisplatin-induced AKI [124].…”

Optimal cumulative dose of cisplatin for concurrent chemoradiotherapy among patients with locally advanced nasopharyngeal carcinoma: a multicenter analysis in Thailand

“…About 13.6% patients with cancer treated with cisplatin develop nephrotoxicity, i.e., acute kidney injury (AKI), which is significantly associated with administrated cisplatin dose [13]. Incidences of nephrotoxicity among head and neck cancer patients receiving cisplatin CRT were 30%-34%, higher than in those with other cancer types [14,15]. Therefore, we evaluated the optimal cisplatin CD for definitive CRT that would maintain efficacy and minimize toxicity among patients with locally advanced NPC in a multicenter setting in Thailand.…”

Alterations in Cisplatin Pharmacokinetics and Its Acute/Sub-chronic Kidney Injury over Multiple Cycles of Cisplatin Treatment in Rats

“…However, despite its clinical usefulness, CDDP-induced nephrotoxicity is one of the dose-limiting side effects and a major clinical concern; recent retrospective studies have reported that approximately one-third of patients treated with CDDP-based chemotherapy experience acute kidney injury (AKI), even with plausible renoprotective strategies such as co-administration with hydration. 1,2) Therefore, the prediction and prevention of CDDPinduced AKI still remain a challenge.…”