The anaemia associated with
cancer can be effectively treated with recombinant human
erythropoietin (rHuEpo) in about 60% of the patients. However, the response rate varies according to treatment modalities as well as the response criteria used. A number of disease- or
chemotherapy-related factors determines the probability of response. Several specific mechanisms of anaemia, such as
haemolysis,
splenomegaly,
bleeding, haemodilution, or ineffective erythropoiesis can seriously interfere with response. However, the type of
tumor, in particular haematologic versus non-haematologic, is not critical, except in situations of major marrow involvement and limited residual haematopoiesis. Stem cell damage by previous
therapy, reflected by low platelet counts or high transfusion needs, will impair response. In addition, marrow suppression by current intensive
chemotherapy will also have a negative impact. Besides its intensity, the type of
chemotherapy may not be critical, although patients undergoing
platinum-based
chemotherapy may respond faster than those receiving non-
platinum regimens. Complications such as
infections,
bleeding or
nutritional deficiencies may have a major negative impact on outcome. An important response-limiting factor is functional
iron deficiency, i.e. an imbalance between
iron needs in the erythropoietic marrow and
iron supply, which depends on the level of
iron stores and its rate of mobilisation. Therefore, oral or preferably intravenous
iron supplements should be given when serum
ferritin is below 40-100 micrograms/l, reflecting the absence of
iron stores, or when the percentage of hypochromic red cells rises above 10%, indicating functional
iron deficiency even in the presence of adequate storage
iron. Because up to 40% of the patients will not respond to rHuEpo, it is of utmost importance to develop models that could help predict response to rHuEpo and thus select the most appropriate
cancer patients for this
therapy. Most studies of patients with myeloma or
lymphoma have indicated that patients with a low baseline serum Epo level will respond better, but this is not true of patients with solid
tumors. Also of considerable interest are early changes of erythropoietic parameters after 2 to 4 weeks of treatment, including increments of serum
transferrin receptor (sTfR), reticulocytes and
haemoglobin, as well as the persistence of elevated
ferritin or Epo levels. Combination of baseline serum Epo and the 2-week increment of sTfR or haemoglobin may provide the best prediction of response.