Researchers from Stanford University have reported that an intra-patient weight-based dose escalation scheme of Aranesp® (darbepoetin) may improve responses in patients with low and intermediate risk myelodysplastic syndromes (MDS). The details of this study appeared in the January 2009 issue of the American Journal of Hematology.[1]

For several years MDS has been treated with recombinant growth factors to decrease anemia and to improve granulocyte levels with some success. Epoetin alfa and, more recently, Aranesp have been effective in treating anemia in some subsets of patients with MDS. Neupogen® (filgrastim) and, more recently, Neulasta® (pegfilgrastim) have also been effective in improving anemia and granulocyte levels in MDS. These supportive care modalities have improved the quality of life of patients with MDS. More recently two drugs, Vidaza® (5-azacytidine) and Dacogen® (decitabine) have been approved by the U.S. Food and Drug Administration as specific therapy for patients with MDS. 

The International Prognostic Scoring System (IPSS) is now commonly used to assign risk groups. However, there have been recent attempts to improve this scoring system. The IPSS  divides patients, based on the percent of marrow blasts, karyotype, and degree of cytopenias into low, intermediate 1, intermediate 2 and high-risk groups, with median survival of 5.6, 3.1, 1.2, and 0.4 years, respectively.

The current study involved 24 patients with low and intermediate 1 MDS treated with Aranesp with or without G-CSF (Neupogen). The novel approach in this Phase II study was to base the dosage of Aranesp on body-weight and to dose-escalate depending on response. Patients were initially treated with 2.5 micrograms/kg/week of Aranesp for six weeks. After six weeks those without a major erythroid response received nine micrograms/kg/wk of Aranesp. After six weeks those without a major erythroid response received G-CSF at a dose of 2.5 micrograms/kg/twice weekly. The median dose of Aranesp was 390 micrograms/kg/week. Twelve patients had a major erythroid response, and four had a minor response; this yielded an overall response rate of 67%. Fifteen patients received G-CSF, and 47% had an erythroid response. Patients with the lowest IPSS scores and the least red cell requirements responded best to this approach. These authors suggest that a weight-based dose escalation may be superior to a fixed dosage schedule of Aranesp.

Comments: It is impossible to tell from this study whether or not the weight-based escalation scheme is superior to the conventional fixed-dose method. However, the responses observed appeared to be at least as good if not better than observed in other trials of Aranesp and G-CSF for low and intermediate-risk MDS. 

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