A Prospectively Randomized Placebo-Controlled Trial of Epoetin-α in Patients with Advanced-Stage Hodgkin Lymphoma: Final Analysis of the GHSG HD15-EPO Trial

Anemia is frequent among cancer patients and impacts organ function and quality of life of those affected. Anemia has been shown to be a negative prognostic factor in several malignancies including Hodgkin Lymphoma (HL). In addition, the advent of more aggressive treatment regimen such as BEACOPP escalated has resulted in more HL patients needing red-blood-cell transfusion. Thus, apart from the chemotherapy-related question of the GHSG HD15 trial, ie 8 cycles of BEACOPP escalated or 6 cycles of BEACOPP escalated or 8 cycles of BEACOPP14, patients in HD15 were randomized between Epoetin-α and placebo. Study drug was given at 40.000 I.E. weekly with a hemoglobin target level of 12–13g/dl. Primary endpoint was fatigue after the end of chemotherapy (CT) and 6 months later measured with the EORTC QLQ-C30 questionnaire (0–100 scale). With respect to the more recent safety discussion related to erythropoetins (EPOs) in general, we also analyzed efficacy and safety endpoints although the trial was not sufficiently powered for time-to-event analyses. Between1/2003 and 12/2006 1.379 patients were randomized for the EPO question of whom 1.329 were eligible. Of these 1.286 (96.8%) are fully evaluable. Patient characteristics were balanced between the placebo and the EPO arm. In those 688 patients who were randomized before 7/2005 and eligible for analysis, the CR/CRu rate was 90, 6% with a median follow-up of 28 months, 58 progressions/relapses (8.4%) and 33 deaths (4.8%) without differences between study arms. There was also no difference in terms of freedom from treatment failure (hazard ratio (HR) 0.9, 95%-confidence interval (CI) 0.6–1.4) and overall survival (HR 1.1, 95% CI 0.6–2.3). 51 serious adverse (7.4%) and 35 thrombovascular events (5.1%) were observed with no significant difference between arms. The median number of red blood cell units given significantly favored patients receiving Epoetin-α (2 vs 4; test for trend p<0.001). The interim analysis for fatigue gave an average value of 61+/−25.8 (mean +/−SD) at the end of treatment and a reduced fatigue score of 33+/−25.3 at six months after CT.

Conclusion: This is the largest prospectively randomized, placebo-controlled trial with EPO in cancer patients. So far we found no difference in terms of fatigue, response, relapse, or side effects between those advanced-stage HL patients receiving Epoetin-α or placebo. The number of RBC units given was significantly reduced in the EPO group. However, all cases are needed for a final conclusion and will be presented.