Impact of acute kidney injury defined by CTCAE v4.0 during first course of cisplatin-based chemotherapy on treatment outcomes in advanced urothelial cancer patients

Clin Exp Nephrol. 2017 Aug;21(4):732-740. doi: 10.1007/s10157-016-1327-z. Epub 2016 Aug 26.

Abstract

Background: The Kidney Disease: Improving Global Outcomes group (KDIGO) defined acute kidney injury (AKI) as an elevation of serum creatinine (sCR) exceeding 0.3 mg/dl within 48 h. The widely used adverse events criteria for chemotherapy, Common Toxicity Criteria for Adverse Events Version 4.0 (CTCAE v4.0), also defined AKI as sCR exceeding 0.3 mg/dl, but with no provision of a time course. Here, we attempted to clarify the impact of AKI (CTCAE v4.0) during cisplatin-based chemotherapy on clinical outcome of patients with advanced urothelial cancer (UC).

Methods: This multicenter retrospective study included 230 UC patients who received cisplatin-based chemotherapy.

Results: During the first chemotherapy course, AKI (CTCAE v4.0) episodes were observed in 61 patients (26.5 %), whereas only four patients (1.5 %) experienced AKI (KDIGO) episodes. Both the pretreatment estimated glomerular filtration rate (eGFR) and creatinine clearance by Cockcroft-Gault formula were not efficient predictors for the development of AKI (CTCAE v4.0). AKI (CTCAE v4.0) impacted renal function: at the start of second-course chemotherapy, the average eGFR of the patients with AKI (CTCAE v4.0) was 54.1 ml/min/1.73 m2, significantly lower than that of patients without AKI (CTCAE v4.0) (63.4 ml/min/1.73 m2). As a result, only 57.4 % of patients with AKI (CTCAE v4.0) received the planned treatment at the second course. The survival of the patients who developed AKI (CTCAE v4.0) was significantly worse than that of the patients who did not. The 3-year OSs were 10.3 and 21.4 %, respectively (P = 0.02).

Conclusion: The present study demonstrated that AKI (CTCAE v4.0) during chemotherapy had a negative impact on both the intensity of subsequent chemotherapy and oncological outcomes.

Keywords: Acute kidney injury; Chemotherapy; Cisplatin; Serum creatinine; Urothelial cancer.

Publication types

  • Multicenter Study

MeSH terms

  • Acute Kidney Injury / blood
  • Acute Kidney Injury / chemically induced*
  • Acute Kidney Injury / diagnosis
  • Acute Kidney Injury / physiopathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Biomarkers / blood
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects*
  • Creatinine / blood
  • Drug Administration Schedule
  • Female
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Japan
  • Kaplan-Meier Estimate
  • Kidney / drug effects*
  • Kidney / metabolism
  • Kidney / physiopathology
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk Factors
  • Time Factors
  • Treatment Outcome
  • Up-Regulation
  • Urologic Neoplasms / drug therapy*
  • Urologic Neoplasms / mortality
  • Urologic Neoplasms / pathology
  • Urothelium / drug effects*
  • Urothelium / pathology

Substances

  • Biomarkers
  • Creatinine
  • Cisplatin