Effect of Dose Reductions on Response to 500-μg Darbepoetin alfa Administered Once Every 3 Weeks for the Treatment of Chemotherapy-Induced Anemia: Analysis from a Randomized, Double-Blind, Active-Controlled Trial.

Background: Darbepoetin alfa (Aranesp®; DA) is an erythropoiesis-stimulating protein (ESP) effective for treating chemotherapy-induced anemia (CIA). Every-3-week (Q3W) administration has been shown to be effective in treating CIA in a randomized, double-blind, double-dummy, active-controlled phase 3 study of 705 patients (pts) (EHA 2005 Meeting: Poster# 0471). We performed an exploratory analysis from this study to investigate the effect of dose reductions/withholding on Hb levels with the extended Q3W dosing compared with QW dosing. Dose titration is important to ensure efficient control of hemoglobin (Hb) levels and to minimize adverse events resulting from rapid increases in Hb. Methods: The study enrolled pts ≥18 years of age, diagnosed with anemia (Hb Results: A high proportion of pts in both Q3W and QW groups had their dose reduced (adjusted KM: 74% [95% CL: 69, 80] for the Q3W group, and 75% [95% CL: 70, 80] for the QW group), predominantly as a result of an Hb increase ≥1 g/dL in 2 wks. The average weekly dose over the entire study was 129.6 (SD 34.7) μg for the Q3W group and 113.0 (SD 42.7) μg for the QW group. The median time to 1st dose reduction was 43 days for the Q3W group (36 days for the QW group), when the mean Hb concentration was 11.15 g/dL. The PME model for Q3W revealed an increase in Hb up to the 1st dose reduction at a mean rate of 0.048 g/dL/day (0.34 g/dL/wk). After 1st dose reduction, Hb was maintained at a relatively steady level until the end of treatment phase with a subsequent slower increase of 0.004 g/dL/day (0.028 g/dL/wk). Examination of Hb profiles after dose withholding from Hb ≥13 g/dL showed no differences between Q3W and QW groups. The safety profiles for the Q3W and QW groups were similar, with no increase in cardiovascular/thromboembolic events associated with rapid increases in Hb. Conclusions: DA administered using a fixed dose Q3W can safely and effectively treat CIA. The PME model confirms that the starting dose of 500 μg Q3W, accompanied by dose reductions in the range of 25–50%, maintains Hb levels in pts with CIA.