Strategies for optimizing hemoglobin response in cancer patients: focus on new epoetin alfa dosing regimens

As the prevalence and impact of anemia in patients with cancer have been recognized, clinical guidelines with recommendations for the use of both transfusions and recombinant human erythropoietin (rHuEPO; epoetin alfa) are continuing to evolve. The strength of recommendations varies depending on the availability of randomized, controlled clinical trial data for a given endpoint, which can include transfusion reduction, improvements in hemoglobin (Hb) levels, quality of life (QOL) improvement, or potential treatment outcome benefits. Clinical studies have shown that epoetin alfa, in doses of 150-300 IU/kg three times a week, consistently increases Hb levels by similar to1 g/dl at 4 weeks and similar to2 g/dl at 8 weeks. A prospective, community-based clinical trial has demonstrated that a once-weekly (QW) regimen of epoetin alfa (40000-60000 I U) increases Hb levels by 1.1 g/dl at week 4 and by 1.7 g/dl at week 8. Results from a second prospective, open-label, community-based trial are consistent with these findings. These increases are associated with statistically significant reductions in transfusion requirements and improvements in QOL. The question as to whether epoetin alfa should be given to patients with mild anemia is currently being evaluated in several early-intervention studies (i.e. in patients with mean Hb similar to12 g/dl). Preliminary results suggest that epoetin alfa, given QW at doses of 40 00060000 IU, prevents Hb decline and may ameliorate deterioration in QOL during chemotherapy in these patients. In addition to studies evaluating early intervention with epoetin alfa, several ongoing studies are examining new epoetin alfa dosages and administration schedules in an effort to optimize Hb correction. For example, investigators are evaluating whether regimens with high initial dosages (60000-80000 IU QW) of epoetin alfa, given for a short period of time, may improve hematologic response in patients with established anemia and whether less frequent maintenance dosing (i.e., 120000 IU every 3 weeks) is sufficient to maintain the Hb response. If high initial epoetin alfa doses followed by infrequent maintenance dosing proves effective in larger clinical trials, a variety of more convenient dosing regimens may be available. (C) 2003 Elsevier Ltd. All rights reserved.