Erythropoietin warning:
As you know there has been a black box warning added to all of the
erythropoietin products (Procrit, Epogen, and Aranesp), due to two forms of
risk:
1) The potential for products that stimulate red cell production to
stimulate tumor growth in patients with breast cancer and head and neck
cancer.
2) The need to monitor very carefully when using red cell production
stimulants in other conditions (including the anemia induced by cancer,
renal failure and HIV medications) due to a risk of blood clots that could
lead to stroke, heart attacks, deep vein thrombosis, and pulmonary
embolism. The deep vein thrombosis risk and pulmonary embolism risk was
also seen in healthy patients receiving the products to control post
operative anemia.
As you know, the University of Miami CFS research team recently completed a
study of erythropoietin, using Procrit, in a phase 2 double blind placebo
control study. While we did not have any of these complications in our
study, patients were monitored very closely and the drug was titered to
very low levels when the red cell expansion exceeded the plasma volume
expansion and caused the blood to thicken. This happened very
frequently, and doses were dropped in many subjects. Doses anywhere close
to the doses suggested in the PDR would be very dangerous and even life
threatening. The study's principal investigator, Dr. Barry Hurwitz
recently reported the results of this phase 2 study at the 8th
International IACFS Conference in Ft Lauderdale. He noted that we were
unable to increase the red cell mass to mid-normal levels with
erythropoietin and salt alone, restricted by safety concerns. At these
lower than projected levels of RBC mass increase, the tilt table test did
show a longer time until the onset or orthostatic hypotension. However,
the patients' overall function and quality of life was not significantly
improved. The results from this phase 2 study are not sufficient to
suggest the use of erythropoietin in CFS patients. Should the
pharmaceutical world like to review our data, and allow us to design a
study that increased the plasma volume in addition to the RBC mass, we
would consider another clinical trial. However, I think our data can be
viewed in another way, as it would appear the inflammatory cytokines play a
role in erythropoiesis suppression. In the future, our studies of
immunomodulators that attempt to quiet the inflammatory cytokines will also
look at the markers of red cell production.
Finally, beware of the new erythropoietin drug, Dynepo, available currently
in Europe. My reading of the literature suggests that the problem with
the EPO drugs currently on the market is that they do their jobs too
well. In the end, it is the act of red blood cell stimulation that induced
the tumor growth, or the over production of red cells in relation to the
plasma. Anything that pushes that button, should, in theory, hold the
same risk. While the new product is derived from human cell lines, I
don't see why the inherent risk would be different. As it took many
patient years for this risk to become evident with the current products, I
would not assume that the lack of vast amounts of safety data is the same
as an all out "don't worry this one is safe" reassurance. Just my take on
a complicated situation!
Sincerely,
Nancy Klimas, MD
Professor of Medicine and
Director CFS/GWI Research Center
University of Miami Miller School of Medicine and the Miami VA Medical Center
Co-PI NIH RO1 HL65668 (the EPO study)
