A randomized, open-label, multicenter trial of immediate versus delayed intervention with darbepoetin alfa for chemotherapy-induced anemia

The optimal hemoglobin concentration at which to initiate erythropoietic therapy for chemotherapy-induced anemia ( CIA) is not well defined. This randomized, open-label, multicenter study evaluated the ability of darbepoetin alfa ( 300 mu g every 3 weeks) to maintain hemoglobin levels >= 10g/dl in patients with CIA ( hemoglobin >= 10.5 g/dl and <= 12.0 g/dl) randomized 1: 1 to an immediate-intervention group ( received darbepoetin alfa immediately) or observation group ( received darbepoetin alfa if hemoglobin fell to < 10 g/dl). In 201 evaluable patients, there was a significant difference between the two groups in the Kaplan-Meier proportion of patients with a hemoglobin decrease to < 10g/dl during weeks 1-13 ( test period) ( primary endpoint): 29% for immediate-intervention patients versus 65% for observation patients. Sixty-four patients in the observation group received darbepoetin alfa ( delayed-intervention subgroup). The Kaplan-Meier proportion of patients who received transfusions was lower in the immediate-intervention group than in the delayed-intervention subgroup ( 14% versus 31% for the test period; 17% versus 36% over the whole study). The target hemoglobin level (>= 11 g/dl) was achieved by a higher percentage of patients ( crude percentage) in less time in the immediate-intervention group ( 94% in 2 weeks) than in the delayed-intervention subgroup ( 73% in 6 weeks); hemoglobin endpoints for the delayed-intervention subgroup were calculated from recalibrated study week 1 ( the date patients first received darbepoetin alfa). For both groups, a higher mean change in hemoglobin from baseline led to a greater improvement in Functional Assessment of Cancer Therapy-Fatigue scores. In conclusion, immediate intervention resulted in a significantly lower proportion of patients who experienced a decline in hemoglobin, lower requirement for transfusions, and greater proportion of patients achieving and maintaining the target hemoglobin level.