Biology Reference
In-Depth Information
Erythropoeitic therapy for patients not receiving chemotherapy
ACD associated with cancer
As noted above,data from the initial Phase II studies of rHuEPO for anemic
patients with cancer not receiving chemotherapy suggested that this population
of patients is more responsive to erythropoietic therapy than patients with can-
cer receiving chemotherapy, and therefore more likely to benefit from therapy
[45, 46]. These observations were buttressed by the results of trials of pre-
operative treatment of cancer patients to increase hemoglobin concentration or
increase autologous blood harvested [47-49]. (See Chapter 12 for more infor-
mation on autologous blood donation.) The experience in these clinical trials
suggests that a relationship exists between the dose of rHuEPO administered
and the observed proportion of responding patients. In the Phase III, placebo-
controlled trial in patients with cancer not receiving chemotherapy,lower
doses of rHuEPO (100 U/kg three times a week) were given and, more impor-
tantly, the study drug was given for only eight weeks [6]. As a result, the trans-
fusion requirements of the two groups, while different in favor of the rHuEPO
group, did not achieve statistical significance.
Dose-finding studies of darbepoetin alfa have been done in patients with
cancer not receiving chemotherapy; these data exhibit a greater proportion of
responding patients to a given dose than has been observed with patients
receiving chemotherapy [50]. These studies clearly show a relationship
between the administered dose of darbepoetin alfa and the proportion of
patients with a hematopoietic response. At the higher doses, response rates as
high as 100% are observed. Moreover, these studies have shown a relationship
between the dose administered and the rapidity of response. In this setting,
hemoglobin concentration increases have been associated with increases in
measured quality of life and productivity. Dosing intervals as infrequent as
every four weeks are feasible with this agent in this setting.
As of this writing, no erythropoietic agent is registered in any country for
the treatment of the anemia of cancer for patients who are not receiving
chemotherapy and most patients with cancer who are treated for anemia are
receiving chemotherapy. Placebo-controlled trials documenting the ability of
erythropoietic agents to provide meaningful benefits, including quality of life,
to patients not receiving chemotherapy are among the most acute needs in the
field of erythropoietic therapy.
Anemia associated with myelodysplastic syndromes
Anemia due to the myelodysplastic syndromes (MDS) is a common and vex-
ing problem in oncology because the anemia is frequently severe enough to
require transfusion support and of sufficient duration to allow the development
of alloimmunization. Although myeloblasts have been reported to bear ery-
