Dose-Conversion Ratio for Epoetin Alfa and Darbepoetin Alfa in Chemotherapy Patients with Anemia and Cancer

Objective: We sought to quantify the dose‐conversion ratio (DCR) between epoetin alfa (EPO) and darbepoetin alfa (DARB), based on a randomized, prospective clinical trial. This study was designed to compare the effectiveness of EPO at a starting dose of 40,000 units once weekly versus DARB at a starting dose of 200 mcg once every two weeks in patients with chemotherapy-induced anemia. Methods: This retrospective secondary analysis used data from an open-label, randomized, multicenter, head-to-head trial comparing EPO with DARB in patients 18 years of age or older with anemia and a solid tumor who were undergoing chemotherapy. Patients received subcutaneous injections of either EPO 40,000 units once weekly or DARB 200 mcg every two weeks for up to 16 weeks. Cyclic chemotherapy was scheduled for a minimum of 12 weeks. The DCR was defined as relative doses between EPO and DARB needed to achieve equivalent effectiveness of treatment. Both cumulative and average weekly doses were used in the dose calculation. The effectiveness measure was the area-underthe-hemoglobin-change curve over the 16-week treatment (Hb AUC 16 ), calculated according to patients’ weekly and monthly Hb change values, respectively. We chose the cumulative dose and the weekly Hb AUC 16 as the base case scenario, and we conducted sensitivity analyses using the average weekly doses and monthly Hb AUC 16 . We used the Delta method and the nonparametric bootstrap procedure to determine the 95% confidence interval (CI) around the DCR point estimate. Results: A total of 346 patients (172 receiving EPO, 174 receiving DARB), formed the study population. There were no significant differences between these groups with respect to sex, race, age, body mass index, or baseline Hb level. The base case scenario corresponded to a DCR of 199:1 (range, 190:1‐207:1) in sensitivity analyses. The 95% CIs derived from each method were comparable. The upper boundary of the DCR confidence limits was systematically lower than 300:1. Conclusion: This study indicated a DCR of 199:1 between EPO and DARB; 199 units of EPO achieved a level of hemato