The Effectiveness of a Fixed Low Dose of Erythropoietin (EPO) in Anemic Solid Tumor Patients Receiving Concomitant Chemotherapy: A Prospective, Randomized, Controlled Study

Erythropoiesis-stimulating agents (ESAs) are indicated for the management of chemotherapy induced anemia in oncology. However, increased risks of cardiovascular events, inferior survival, and poorer tumor outcomes are linked to ESAs when used to achieve a target hemoglobin ≥12 g/dL. Due to these serious safety concerns, the FDA has recommended more conservative dosing guidelines whereby the lowest possible dose of ESAs should be used to gradually increase hemoglobin concentration to the lowest level sufficient to avoid blood transfusion. The currently ASCO/ASH recommended and FDA approved starting dose for epoetin is 150 U/kg three times weekly (TIW) or 40,000 U weekly, and the dose should be increased to 300 U/kg or 60,000 U in nonresponsive patients.

This study evaluated the effectiveness of a fixed lower dose (4000 unit, TWI) of Epoetin alfa (Epo a) in comparison with transfusion support alone in anemic solid tumor patients (Hb< 9 g/dl) who were administered concomitant chemotherapy.

This was a prospective, single-centered, randomized, controlled study. The period of enrollment began in June 2009 and ended in December 2010. A total of a hundred and two solid tumor patients with chemotherapy induced anemia (Hb < 9 g/dl) and Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0–3 were enrolled and randomized into two groups; forty five patients (treatment arm) received 4000 unit of Epo a three times weekly plus oral iron, whereas fifty seven patients were randomized to control group (control arm). Both groups received RBC transfusion when needed. Epo dose was not increased in patients deemed nonresponsive. The primary endpoints were the changes in hemoglobin (Hb) concentrations, transfusion needs, and QoL. The follow-up period was twelve weeks.

Mean age of 102 patients was 53.6 ±12.7 years (mean ± SD), mean weight was 63.86 ±12.05 kg (mean ± SD), mean hemoglobin was 8.22 ± 0,55 g/dl (mean ± SD), 32.4% were male, and 60.8% were on platinum based chemotherapy.

After excluding patients who died, were lost to follow up, withdrew consent, or were ineligible, 81, 59, and 50 patients were assessed at weeks 4, 8, and 12 respectively. At each of these time points, Epo at low dose (4000 unit, TWI) significantly decreased transfusion needs, increased hemoglobin concentrations, and improved QoL.

At week 12, the mean hemoglobin increase was 2.4 g/dL in the EPO group (n=28) versus 0.97 g/dL in the control group (n=22) (P < 0.001). In Epo-responders (17/28), Hb increase was 2.87 g/dl, and Hb concentrations were > 12 g/dl in 5/17 (29.4%), 11–12 g/dl in 3/17 (17.64%), and 10–10.9 in 3/17 (17.64%).

EPO evaded blood transfusion in 19/28 patients (67.87%) in the EPO arm. 9/28 (32.14%) of patients in the EPO arm were transfused a total of 18 units (0.65 unit per patient), versus 21/22 (95.45%) in the control group who received a total of 53 units, resulting in a significantly higher average transfused units per patient (2.41 units per patient) (p < 0.001).

Based on ECOG PS score, QoL was significantly better in Epo treatment group in comparison with control group (p< 0.05).

Administration of EPO in a low dose (4000 U, TIW) is effective in alleviating anemia, evading RBC transfusions, and improving QoL in a considerable proportion of anemic cancer patients receiving chemotherapy. Our findings highlight a great variation in responsiveness to low dose of EPO in anemic cancer patients and suggest the existence of high EPO responders. Lowering the starting dose of Epo may represent a more physiologic and effective alternative that better corresponds to FDA recommendations.

No relevant conflicts of interest to declare.