Carboplatin Dosing in the Treatment of Ovarian Cancer: An Nrg Oncology Group Study

Authors

Aaron M Praiss
Austin Miller
Judith Smith
Stuart M Lichtman
Michael Bookman
Carol Aghajanian
Paul Sabbatini
Floor Backes
David E Cohn
Peter Argenta
Michael Friedlander
Michael J Goodheart
David G Mutch
David M Gershenson
Krishnansu S Tewari
Robert M Wenham
Andrea E Wahner Hendrickson
Roger B Lee
Heidi Gray
Angeles Alvarez Secord
Linda Van Le
Roisin E O'Cearbhaill

Publication Date

7-1-2023

Journal

Gynecologic Oncology

Abstract

Objective: To determine the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and explore adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl).

Methods: Retrospective data were obtained for 3830 of 4312 patients treated on GOG182 (NCT00011986)-a phase III trial of platinum-based chemotherapy for advanced-stage ovarian cancer. Carboplatin dose per patient on GOG182 was determined using the Jelliffe formula. We recalculated CrCl to determine dosing using Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (with/without NCCN recommended modifications) formulas. Associations between baseline CrCl and toxicity were described using the area under the receiver operating characteristic curve (AUC). Sensitivity and positive predictive values described the model's ability to discriminate between subjects with/without the adverse event.

Results: AUC statistics (range, 0.52-0.64) showed log(CrClJelliffe) was not a good predictor of grade ≥3 adverse events (anemia, thrombocytopenia, febrile neutropenia, auditory, renal, metabolic, neurologic). Of 3830 patients, 628 (16%) had CrCl < 60 mL/min. Positive predictive values for adverse events ranged from 1.8%-15%. Using the Cockcroft-Gault, Cockcroft-Gault with NCCN modifications, and MDRD (instead of Jelliffe) formulas to estimate renal function resulted in a >10% decrease in carboplatin dosing in 16%, 32%, and 5.2% of patients, respectively, and a >10% increase in carboplatin dosing in 41%, 9.6% and 12% of patients, respectively.

Conclusion: The formula used to estimate CrCl affects carboplatin dosing. Estimated CrCl < 60 mL/min (by Jelliffe) did not accurately predict adverse events. Efforts continue to better predict renal function. Endorsing National Cancer Institute initiatives to broaden study eligibility, our data do not support a minimum threshold CrCl < 60 mL/min as an exclusion criterion from clinical trials.

Keywords

Female, Humans, Carboplatin, Creatinine, Glomerular Filtration Rate, Kidney Function Tests, Ovarian Neoplasms, Retrospective Studies, Carboplatin dosing, Cockcroft-Gault formula, Creatinine clearance, Jelliffe formula, Modification of diet in renal disease formula, Wright formula

DOI

10.1016/j.ygyno.2023.05.013

PMID

37229879

PMCID

PMC10330633

PubMedCentral® Posted Date

7-1-2024

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes