Carboplatin dosing in the treatment of ovarian cancer: An NRG oncology group study
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). 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. AUC statistics (range, 0.52-0.64) showed log(CrCl 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.
Journal
Gynecologic OncologyAuthors
Funding
NRG Oncology Network Group Operations CenterUniversity of Buffalo Clinical and Translational Science InstituteCancer Center Support GrantPathologyNetwork Lead Academic Participating Site Grant from the Roswell Park Cancer InstituteSWOG Network Group Operations Center of the NCTNData Management CoreWashington University/Siteman Cancer Center Lead Academic SiteLead Academic Participating Site: Memorial Sloan Kettering Cancer CenterOSU as a Network Lead Academic Participating Site for the NCI NCTN