Recombinant human erythropoietin therapy for anemic cancer patients on combination chemotherapy. Prevention of chemotherapy-induced anemia by the use of erythropoietin in patients with primary malignant bone tumors (a double-blind, randomized, phase III study).
Patients with advanced cancer frequently experience clinically significant anemia, which is often exacerbated by myelosuppressive chemotherapy. Consistent with the anemia of chronic disease, studies have documented serum erythropoietin levels that are inappropriately low for the degree of anemia in cancer patients. Myelosuppressive chemotherapy impairs erythropoiesis, which may not fully recover between treatment cycles. Recombinant human erythropoietin (rHuEPO) has been used safely and effectively to treat anemia in AIDS patients receiving zidovudine (AZT) and in patients with chronic renal failure.
                This study was designed to evaluate the clinical role of rHuEPO in reducing symptomatic anemia in patients with advanced cancer who were receiving myelosuppressive chemotherapy (excluding cisplatin).
                We studied 153 anemic cancer patients receiving cyclic combination chemotherapy in a prospective multicenter, double-blind, placebo-controlled trial. The patients were randomly assigned to receive either rHuEPO (150 U/kg) or placebo subcutaneously three times a week for a maximum of 12 weeks or until the hematocrit level increased to 38%-40%. If the hematocrit reached this target level before 12 weeks, the rHuEPO dose could be reduced to maintain the hematocrit at that level for the duration of the study. Response to rHuEPO therapy was assessed by measuring changes in hematocrit level, transfusion requirements, and quality of life. Quality-of-life assessment was based on patients' responses to questionnaires before and after the courses of therapy.
                The increase in hematocrit in the rHuEPO-treated group compared with hematocrit in the placebo-treated group was statistically significant (P = .0001) as measured by percentage point of change from baseline to final evaluation, by an increase in hematocrit level of six percentage points or more unrelated to transfusion, and by a rise in hematocrit level to 38% or more unrelated to transfusion. There was a trend toward the reduction in mean units of blood transfused per patient during months 2 and 3 of therapy combined in rHuEPO-treated patients compared with placebo-treated patients (0.91 U versus 1.65 U; P = .056). In addition, rHuEPO-treated patients experienced a statistically significant improvement in energy level and ability to perform daily activities (P < or = .05). The two treatment groups showed no statistically significant differences in toxic effects except for increased incidence of diaphoresis (P < .05) and diarrhea (P = .05) in the rHuEPO-treated group.
                We conclude that rHuEPO is safe and effective for reversing anemia related to advanced cancer or to chemotherapy for cancer. Patients undergoing chemotherapy for treatment of malignancy frequently experience clinically significant anemia. Myelosuppressive chemotherapy impairs erythropoiesis, which may not fully recover between treatment cycles. Recombinant human erythropoietin (rHuEPO) has been effectively introduced in anemic patients suffering from chronic renal failure. The present study was designed to assess, first, whether rHuEPO treatment decreases transfusion requirements in chemotherapy-induced anemia and, second, whether high-dose rHuEPO application is safe. STUDY DESIGN and
                Thirty consecutive anemic patients (hemoglobin <11 g/dl) receiving combination chemotherapy for primary malignant bone tumors were studied in a prospective, double-blind, randomized, Phase III trial. Patients received chemotherapy according to one of two German protocols, depending on histologic diagnosis. All subjects enrolled were randomly assigned either to receive 600 IU of rHuEPO per kg of body weight intravenously twice a week or to receive a placebo during chemotherapy. To obtain comparable data, an observation period of 20 weeks was chosen. Twenty-nine patients fulfilled the criteria and were eligible for statistical evaluation.
                Transfusion requirements were significantly decreased from Week 8 of therapy (p<0.05) in the treatment group. Therapeutic benefits were even more evident with continuation of therapy (Week 12, p = 0.03; Week 16, p = 0.016; Week 20, p = 0.002). The blood required was 2.1 units of red cells in the treatment group and 8.4 units of red cells in the placebo group. All patients tolerated rHuEPO with no serious side effects.
                These findings suggest that rHuEPO is an effective and well-tolerated therapeutic option for decreasing the transfusion requirements in chemotherapy-induced anemia.
This updated Cochrane review provides evidence that rHuEPO compared with placebo does not reduce mortality, does not reduce transfusion requirements, did not increase hemoglobin levels, and did not improve quality of life in HIV-infected patients with anemia. The results are based on six RCTs with high risk of bias. Therefore prescription of this intervention for treating anemia in patients with AIDS is not justified, unless new evidence from a large high quality trial alters this conclusion.