Blogger's Note: note ties to industry
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"Erythropoiesis-stimulating agents (ESAs) increase red blood cell (RBC)
production in bone marrow by activating the erythropoietin receptor
(EpoR) on erythrocytic-progenitor cells. Erythropoiesis-stimulating
agents are approved in the United States and Europe for treating
anaemia
in cancer patients receiving chemotherapy based on randomised,
placebo-controlled trials showing that ESAs reduce RBC transfusions.
Erythropoiesis-stimulating agent-
safety issues include thromboembolic
events and concerns regarding whether ESAs increase disease progression
and
/or mortality in cancer patients. Several
trials have reported an association between ESA use and increased
disease progression and
/or mortality, whereas
other trials in the same tumour types have not provided similar
findings.
This review thoroughly examines available evidence regarding
whether ESAs affect disease progression. Both clinical-trial data on
ESAs and disease progression, and preclinical data on how ESAs could
affect tumour growth are summarised. Preclinical topics include (i)
whether tumour cells express EpoR and could be directly stimulated to
grow by ESA exposure and (ii) whether endothelial cells express EpoR and
could be stimulated by ESA exposure to undergo angiogenesis and
indirectly promote tumour growth.
Although assessment and definition of
disease progression vary across studies, the current clinical data
suggest that ESAs may have little effect on disease progression in
chemotherapy patients, and preclinical data indicate a direct or
indirect effect of ESAs on tumour growth is not strongly supported."
"This review summarised results from clinical and preclinical studies
that evaluated whether ESAs affect disease progression. Although there
are important limitations on the quality and assessment of disease
progression in these studies, the current meta-analyses suggest no
overall effect of ESAs on disease progression. Several individual
studies have shown a potential trend associating ESA use with increased
disease progression. This suggests that ESAs may affect disease
progression in particular cancer patient populations (e.g., head and
neck cancer patients receiving radiotherapy only) and that additional
research is needed to define these populations and how ESAs mediate this
effect. Although indirect effects on tumours induced by increased RBC
production are theoretically possible, preclinical data to date suggest
that tumour cells either do not express EpoR or express low levels of
EpoR molecules that are non-functional and
/or
are not present at the cell surface. Overall, the balance of current
evidence does not support an effect of ESAs on either activating EpoR on
tumour cells or indirectly stimulating disease progression via
angiogenesis. Future clinical trials, meta-analyses, and preclinical
research should provide additional data to guide evidence-based use of
ESAs in cancer patients."
