Trial Information

A Randomized, Multi-Center Study to Assess the Effect of Darbepoetin Alfa (Aranesp®) for the Treatment of Anemia in Patients With Advanced Hormone Independent Prostate Cancer and Anaemia

In the past, prostate cancer has been regarded a relatively benign disease, which elderly
men were expected to die with rather than from, however, prostate cancer has become the
second most common non-skin cancer in Danish men and the second most common cause of male
cancer death. Two out of three patients with clinically significant prostate cancer die from
and not with their cancer disease, and the misery of this population is evident. Regular
treatments with opiates or equivalent drugs as well are required in nearly one third of the
patients.

Patients with advanced hormone insensitive (refractory) prostate cancer have a median
survival rate of about one year and during this time they often suffer from anemia due to
reasons like blood loss, tumor infiltration of the bone marrow and even treatment with
androgen deprivation. Compared to patients with other cancer types patients with prostate
cancer have a significantly lower mean haemoglobin level. However, patients with hormone
refractory prostate cancer have not previously been given much attention and the treatment
of the frequent condition of chronic anemia in this group of patients seems casual.
Therefore, Best Standard of Care (BSC) is defined as RBC transfusion if the hemoglobin is <
5,0 mmol/L (8,0 g/dl), and if there are signs or symptoms of anemia and supplemental iron if
se-ferritin < 200 mcg/L.

Very little is known about erythropoietin treatment and quality of life in hormone
refractory prostate cancer patients. A randomized Swedish study did investigate the
influence of two different doses of epoetin beta on quality of life, hemoglobin level, need
for red blood cell transfusion and safety, in the treatment of anemia in 180 patients
suffering from advanced hormone-refractory prostate cancer. This study found the treatment
to be safe and effective for the treatment in many of these patients. In many of these
critically ill patients, the treatment improved quality of life and relieved fatigue
symptoms.

Darbepoetin alpha (Aranesp®) is produced by gene-technology in Chinese Hamster Cells
(CHO-K1). It has a biological effect and toxicity profile comparable to r-HuEPO; with the
exception of a longer half-life which means that it can be administered less frequently
without loosing clinical efficiency. Aranesp® has been well tolerated in studies conducted
to this date. In this setting Aranesp® appears to be safe and well tolerated. Adverse events
reported to date have generally been mild to moderate in severity and consistent with events
and symptoms in cancer patients with chronic disease receiving chemotherapy (i.e. fatigue
and gastrointestinal symptoms). Clinical studies have shown a higher frequency of
thromboembolic reactions including deep vein thrombosis and pulmonary embolism in cancer
patients receiving Aranesp therapy compared to patients receiving placebo. The clinical
experience so far with Aranesp® has been published (15,16,17). Aranesp® is registered for
clinical use in Europe and US.

Based on this the present study will evaluate the effect of Aranesp® on the haematopoietic
response in patients with advanced hormone independent prostate cancer and anemia. Moreover,
the effect of Aranesp® on quality of life, hemoglobin, necessity for RBC transfusion and
hospital admissions, will be evaluated. The study will be performed as an open randomized
trial. The use of r-HuEPO in cancer patients has been established and registered in other
settings (as supportive treatment), and it has been shown that the preparation can be given
without significant side effects. On the contrary, it is likely that patients may benefit
from additional improvement in wellbeing.