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.