Association of mannitol (MAN) with cisplatin (CIS)-induced nephrotoxicity (NTX) and cumulative CIS dose (CCD).

Abstract

6051 Background: CIS is widely used in cancer therapy with CCD linked to survival outcome. CCD, however, is constrained by side effects—particularly NTX (incidence 20-30%). MAN is widely used to prevent CIS NTX despite low level of evidence. Herein, we took advantage of a national shortage of MAN to examine renoprotective effects of MAN in CIS treated patients. Methods: Between 2006-2012, 704 consecutive pts undergoing CIS therapy, with or without MAN, were analyzed. Pt characteristics, oncologic diagnosis, treatment, and renal function data were collected. The primary objective was to compare clinically significant NTX, as defined by > 25% reduction in glomerular filtration rate (GFR) from baseline, between the treatment groups. Cox proportional hazards regression was used to model the hazard of NTX as a function of CIS dose. Results: Of 704 pts, 442 were treated with MAN and 262 without. The median age was 58.9 years. Age (p = 0.83), gender (p = 0.77), and race (p = 0.056) were similar between groups whereas baseline GFR (MAN 91.2 ± 22; CIS 86.3 ± 24; p = 0.005) and diagnoses (p < 0.001) differed. The distribution of diagnoses was: head and neck (25.9%), genitourinary (26.0%), lung (14.3%), gastrointestinal (10.4%), lymphoma (4.5%), and other (18.9%). The mean CIS dose (mg) per cycle in MAN versus CIS only group was 126.1 ± 58 and 109.3 ± 58 respectively (p < 0.001). The CCD (mg) was higher in the MAN compared to the CIS only group (469.8 ± 295 versus 299.0 ± 241; p < 0.001). After adjusting for baseline GFR, age, gender, race, and diagnoses, the MAN group experienced lower risk of > 25% decrease in GFR at any given CCD (HR: 0.68, CI: 0.51-0.91, p = 0.01). Females (HR: 1.72, CI: 1.28-2.32; p = 0.0003), older pts (HR: 1.24, CI: 1.10-1.40; p = 0.0003), and Hispanic pts (HR: 2.39, 1.04-5.50; p = 0.04) were more likely to sustain > 25% reduction in GFR. Conclusions: MAN enhances CCD by protecting against CIS-induced NTX. Pts with MAN experienced a lower risk of clinically significant acute kidney injury (AKI) and received a higher average CIS dose per cycle and CCD. Women, older pts, and Hispanic pts had a higher risk of AKI. Future investigation is warranted to examine whether MAN-associated CCD effects translate into survival advantages.