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BACKGROUND The effect of using fixed versus weight‐based doses for erythropoietic agents has not been reported previously. To investigate this issue, the authors conducted a randomized Phase II study of darbepoetin alfa administered as either a fixed dose or a weight‐based dose using an accelerated correction and maintenance dosing regimen (front‐loading). METHODS During the correction phase, patients with anemia (hemoglobin < 11.0 g/dL) who had nonmyeloid malignancies and who were receiving chemotherapy were given darbepoetin alfa at a fixed dose of 325μg (n = 122) or at a weight‐based dose of 4.5 μg/kg (n = 120) once weekly until they achieved a hemoglobin concentration ≥ 12.0 g/dL. Patients then received darbepoetin alfa (325 μg or 4.5 μg/kg) once every 3 weeks for the remainder of the 16‐week treatment period (maintenance phase). RESULTS Darbepoetin alfa resulted in high Kaplan–Meier rates of hematopoietic response (≥ 2 g/dL increase from the baseline level or a hemoglobin level ≥ 12 g/dL) in both the fixed‐dose group (86%; 95% confidence interval [95% CI], 78– 94%) and the weight‐based dose group (84%; 95% CI, 76–92%). The median time to hematopoietic response was 34 days (95% CI, 28–44 days) for the fixed‐dose group and 36 days (95% CI, 30–45 days) for the weight‐based dose group. Hemoglobin concentrations were maintained at target levels for up to 16 weeks in both groups. Darbepoetin alfa was well tolerated, and no clinically significant differences between fixed doses and weight‐based doses were observed. CONCLUSIONS Darbepoetin alfa was effective when administered as either a fixed dose or a weight‐based dose using a front‐loading approach to rapidly correct anemia and effectively maintain hemoglobin levels in patients with anemia who had malignant disease. Cancer 2004;100:859–68. © 2004 American Cancer Society.

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Background Estrogen receptor beta (ERβ) is expressed by 50-80% of triple negative breast cancers (TNBC). Agonism of ERβ has antiproliferative effects in TNBC cells expressing ERβ. This phase II study evaluated single agent high dose estradiol in patients with advanced TNBC. Patients and Methods Adult women with measurable advanced TNBC were treated with estradiol 10 mg oral three times daily given continuously for 28-day cycles. A Simon optimal two-stage design was used. The primary endpoint was objective response (OR). Secondary endpoints included progression-free survival (PFS), clinical benefit (CB), and safety. OR, CB and PFS by ERβ status were also examined. Results Seventeen evaluable women were enrolled. Median age was 58 (34-90); the median number of prior systemic therapies was 2 (0-6). One patient had a confirmed partial response (OR rate of 5.9%) and remained on study for >24 weeks. Three patients had stable disease, one lasting more than 16 weeks. ERβ expression was detected in 77% (13 patients). The CB rate at 16 weeks was 15% (2 of 13) in ERβ positive patients and 0% (0 of 4) in ERβ negative patients (p= 1). PFS was poor (median 1.9 months) and not statistically significantly different between ERβ-positive versus negative patients. No new adverse events from estradiol were identified. The study closed after the first stage due to limited responses in these unselected patients. Conclusions In unselected TNBC, high dose estradiol has limited efficacy. However, further evaluation of ERβ selective agonists in TNBC selected by ERβ expression may be warranted.