Maximum Haemoglobin Level Set for Epoetins Because of Cancer Risk

By Richard Woodman

LONDON JUN 09, 2005 (Agence de Presse Medicale for Reuters Health) - The label on epoetin medications is being updated with a new maximum haemoglobin level following studies showing increased mortality at high haemoglobin levels, a senior Amgen official said on Thursday.

Mark Sampson, UK medical director, told APM that the label would set a therapeutic haemoglobin objective of 12g/dL, coupled with a recommendation not to exceed 13g/dL.

The European Medicines Agency announced on Wednesday that the labels of all epoetins, including Amgen"s Aranesp and Roche"s NeoRecormon, were being changed but gave no details of the new recommendations. Officials still did not return calls on Thursday.

Sampson said Amgen had agreed to the new labels in the light of the Henke and BEST studies in The Lancet and Lancet Oncology, which showed an increased risk of death in cancer patients taking epoetins.

"The studies have shown something that we are not sure about. Until we know more about it, it is a sensible precaution to say that in routine clinical practice you should not raise haemoglobins to high levels. There is no concern at lower levels," he added.

Roche said on Thursday it still did not have details of the revised Summary of Product Characteristics. 

The Roche-funded Henke study, reported in the October 18th issue of The Lancet in 2003, was a randomized trial of 351 head and neck cancer patients with anemia who were treated with radiotherapy. Compared with controls, patients in the epoetin group were 69% more likely to experience locoregional progression and 39% more likely to die.

The BEST study (Lancet Oncology 2003;4:459-460) was a breast cancer trial with erythropoietin that was terminated unexpectedly because of an observed higher mortality in the group treated with Johnson & Johnson"s Eprex. It involved 939 patients who were included in the study if their haemoglobin concentration was 13 g/dl. The goal of treatment was to keep this concentration within the normal range (>12 g/dL and <14 g/dL), irrespective of chemotherapy treatment.

An analysis of 12-month survival, the primary endpoint, showed a statistically significant difference between patients in the placebo group (76%) and those in the Eprex group (70%). Subsequent follow-up beyond the treatment period showed convergence of the survival curves at 19 months.

The 1-year survival difference was due mainly to an increase in mortality in the first 4 months of the study (41 deaths in the Eprex group and 16 deaths in the placebo group). The observed difference in number of early deaths was mainly due to an increase in incidence of disease progression in the Eprex group compared with the placebo group (6% vs 3%) as well as an increase in the incidence of thrombotic and vascular events in the Eprex group (1% vs 0·2%).


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