Evaluation of predictive factors for response to darbepoetin alfa (DA): A prospective study

Abstract

18514 Background: Therapy with erythropoiesis-stimulating factors (ESF) can ameliorate the anaemia associated with cancer and chemotherapy, reduce the need for transfusions and improve quality of life. However, as many as 30–50% of pts. do not respond, even to very high doses of ESF. Methods: In January 2003, we commenced a prospective phase-2 study to evaluate the value of predictive factors for response to DA. The following 5 factors, which had been previously determined as predictive factors in several retrospective studies, were investigated: serum erythropoietin &lt; 100 mU/ml before therapy (Epo-d0); increase in reticulocytes &gt; 40,000/μl (Reti-d14) and in soluble transferrin receptor ≥ 25% (sTfR-d14), both after 2 weeks; increase in reticulocytes &gt; 40,000/μl (Reti-d28) and in Hb &gt; 1 g/dl (Hb-d28), both after 4 weeks. Response was defined as Δ Hb &gt; 2 g/dl or Hb ≥ 12 g/dl within 8–12 weeks. Pts. with solid tumours receiving chemotherapy, ECOG &lt; 2 and Hb &lt; 11g/dl or significant decrease in Hb &gt; 1.5 g/dl within 4 weeks received DA 150 μg/QW or 300 μg/Q2W sc. and 300 μg/QW if Hb &lt; 1 g/dl at d28. Results: Between 01/03 and 09/05 196 pts., 112 female and 84 male, median age 66 years, were treated and evaluated for response. 119 pts. (60.7%) had a response as defined (PP analysis: 68.3%). The predictive value of the 5 factors are given in the Table . In a multiple logistic regression analysis of all 5 factors the ROC has an AUC of 0.78 (95% CI 0.71–0.84). The reduced logistic classification rule (with cutoff 0.5) based on an increase in sTfR &gt; 25% on day14, reticulocytes &gt; 40,000/μl and Hb &gt; 1 g/dl, both on day 28, had the same AUC and its positive / negative predictive value was 88.1% (=74/84) and 59.8% (=67/112) respectively. Conclusions: In contrast to observations made in pts. with lymphoproliferative malignancies, the pretherapeutic serum erythropoietin level has no or very little predictive value for response to DA in anaemic pts. with solid tumours. Supported by AMGEN, Germany with an unrestricted grant. [Table: see text] [Table: see text] </jats:p