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Incidence of Severe Nephrotoxicity With Cisplatin Based on Renal Function Eligibility Criteria: Indirect Comparison Meta-analysis

Dahal, Arati PhD; Bellows, Brandon K. PharmD; Sonpavde, Guru MD; Tantravahi, Srinivas K. MD; Choueiri, Toni K. MD; Galsky, Matthew D. MD; Agarwal, Neeraj MD

American Journal of Clinical Oncology: October 2016 - Volume 39 - Issue 5 - p 497–506
doi: 10.1097/COC.0000000000000081
Original Articles: Normal Tissue Toxicity

Background: The objective of this meta-analysis was to indirectly compare incidence of nephrotoxicity in trials using cisplatin (CIS) for treatment of solid tumors when renal function was assessed using serum creatinine (SCr) or creatinine clearance (CrCl) for eligibility criteria.

Methods: Randomized trials comparing CIS-containing with non-CIS-containing chemotherapy regimens were identified in PubMed. Included studies were performed from 1990 to 2010, used SCr or CrCl as an eligibility criterion, and reported incidence of grade ≥3 nephrotoxicity for both treatment arms using World Health Organization (WHO) or National Cancer Institute (NCI) toxicity criteria. The relative risk (RR) of grade ≥3 nephrotoxicity associated with CIS versus non-CIS regimens was examined. Subgroup analyses, adjusted indirect comparison, and metaregression were used to compare SCr and CrCl.

Results: The literature search identified 2359 studies, 42 studies met all the inclusion criteria (N=9521 patients). SCr was used as an eligibility criterion in 20 studies (N=4704), CrCl was used in 9 studies (N=1650), and either was used in 13 studies (N=3167). The overall RR for developing nephrotoxicity with CIS versus non-CIS treatment was 1.75 (P=0.005). Subgroup analyses showed an increased risk when SCr was used (RR=2.60, P=0.005) but not when CrCl was used (RR=1.50, P=0.19). Both the adjusted indirect comparison and metaregression showed a nonsignificantly reduced risk of nephrotoxicity when CrCl was used.

Conclusions: CIS-based therapy was associated with a significant increase in severe nephrotoxicity. The risk of severe nephrotoxicity appears to be lower when CrCl was used to determine whether people should be treated with CIS.

*Department of Health Services, School of Public Health, University of Washington, Seattle, WA

Pharmacotherapy Outcomes Research Center

§Huntsman Cancer Institute, University of Utah, Salt Lake City, UT

UAB Comprehensive Cancer Center, Birmingham, AL

Dana-Farber Cancer Institute, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA

The Tisch Cancer Institute at Mount Sinai Medical Center, Mount Sinai School of Medicine, New York, NY

A.D. and B.K.B.; and M.D.G. and N.A. contributed equally.

The authors declare no conflicts of interest.

Reprints: Neeraj Agarwal, MD, Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Ste 2123, Salt Lake City, UT 84112. E-mail:

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