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Mannitol dosing and cisplatin-induced acute nephrotoxicity

Date

09 Oct 2016

Session

Poster display

Presenters

Patwant Dhillon

Citation

Annals of Oncology (2016) 27 (6): 497-521. 10.1093/annonc/mdw390

Authors

P. Dhillon, E. Amir, M. Lo, A. Kitchlu, P. Yip, C. Chan, S. Cochlin, E. Chen, R. Lee, P. Ng

Author affiliations

  • Pharmacy, Princess Margaret Hospital, M5G 2M9 - Toronto/CA
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Background

Nephrotoxicity is a dose-limiting adverse effect of cisplatin. Mannitol is an osmotic diuretic given routinely as part of cisplatin regimens to prevent nephrotoxicity. There are limited data on the ideal dose of mannitol. At our centre, 3 different doses are used: 12 g, 20 g, and 40 g /cycle for cisplatin doses of ≥ 50 mg/m2.

Methods

A case-control study was performed. Electronic records of 1462 sequential outpatients who received cisplatin at ≥ 50 mg/m2 /cycle from 2010 to 2014 were reviewed. Patients experiencing acute nephrotoxicity of any grade within 30 days of last cisplatin dose (as defined by the National Cancer Institute Common Terminology Criteria for Adverse Effects version 4) were matched to a minimum of 2 and maximum of 5 controls based on the following criteria: age +/- 5 years; baseline estimated glomerular filtration rate (eGFR) +/- 10 mL/min/1.73m2; cisplatin dose per cycle; and presence of diabetes. Conditional logistic regression was used to identify baseline predictors of cisplatin-induced acute nephrotoxicity.

Results

Of the 1245 included patients, 237 had nephrotoxicity and 1008 were matched controls. Median baseline eGFR for cases and controls were 83 and 80 mL/min/1.73m2, respectively. 3.8% of cases experienced ≥ grade 3 nephrotoxicity. Univariable analysis showed that diabetes, baseline eGFR, and baseline magnesium level were significantly associated with nephrotoxicity, whereas mannitol dosing did not show any association (odds ratio [OR] 1.08, p = 0.29). In multivariable analysis, diabetes (OR 1.86, p = 0.004) retained statistical significance, but baseline eGFR (OR 1.01, p = 0.06) and baseline magnesium level (OR 0.25, p = 0.08) showed non-significant associations with nephrotoxicity. Age, diabetes, cisplatin dose per cycle, mannitol dose per cycle, baseline eGFR, and baseline magnesium level were not predictors for severity of nephrotoxicity.

Conclusions

Cisplatin-induced acute nephrotoxicity remains common despite preventive measures in patients with good baseline renal function. Diabetes is a predictor of nephrotoxicity, whereas mannitol dosing has no significant influence, suggesting that doses may be standardized across cisplatin regimens.

Clinical trial identification

Legal entity responsible for the study

University Health Network

Funding

University Health Network

Disclosure

All authors have declared no conflicts of interest.

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