The following is a summary of “Carboplatin dosing in the treatment of ovarian cancer: An NRG oncology group study,” published in the July 2023 issue of Gynecologic Oncology by Praiss et al.

This study aims to ascertain the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and to investigate adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl). About 3,830 of 4,312 patients treated on GOG182 (NCT00011986), a phase III trial of platinum-based chemotherapy for advanced-stage ovarian cancer, had retrospective data collected. Using the Jelliffe formula, the carboplatin dose per GOG182 patient was calculated. Using the Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (with/without NCCN-recommended modifications) formulas, the researchers recalculated CrCl to determine dosing. 

Using the area under the receiver operating characteristic curve (AUC), associations between baseline CrCl and toxicity were characterized. The model’s ability to distinguish between subjects with and without adverse events was characterized by its sensitivity and positive predictive value. Log(CrCl_Jelliffe) was not an accurate predictor of adverse events of grade ≥3 (anemia, thrombocytopenia, febrile neutropenia, auditory, renal, metabolic, and neurologic). Around 628 out of 3,830 patients (16%) had a CrCl of <60 mL/min. Positive predictive values ranged from 1.8% to 15% for adverse events. 

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, and an increase of >10% in 41%, 9.6%, and 12% of patients, respectively. The CrCl estimation formula influences carboplatin dosage. Jelliffe’s estimated CrCl<60 mL/min did not accurately predict adverse events. Efforts continue to improve renal function prediction. Despite the National Cancer Institute’s initiatives to expand study eligibility, their data do not support a minimum threshold of CrCl<60 mL/min as an exclusion criterion for clinical trials.

Source: sciencedirect.com/science/article/abs/pii/S0090825823002524