ABSTRACT
BACKGROUND: Severe anaemia is common in patients with metastatic, hormone-refractory prostate cancer (HRPC). PATIENTS AND METHODS: We evaluated the efficacy of epoetin beta in correcting anaemia and maintaining haemoglobin (Hb) levels in this group of patients. Patients with HRPC, bone metastases and anaemia (Hb < 12 g/dl) were included. Epoetin beta, 30,000 IU per week in three divided doses, was administered subcutaneously, with iron supplementation when needed. If Hb increased by < 1 g/dl during the first 4 weeks of therapy the epoetin dose was increased (increments of 5,000 IU per dose) at fortnightly intervals to a maximum of 60,000 IU per week. Patients with haematopoietic response (Hb increase > or = 2 g/dl from baseline or Hb level > or = 12 g/dl without blood transfusions) went on to receive epoetin beta 10,000 IU once weekly for up to 24 weeks. RESULTS: All 29 evaluable patients demonstrated a haematopoietic response to epoetin beta treatment. None of the patients required blood transfusions. All patients showed improvements in quality of life (assessed using the EORTC QLQ-C30 questionnaire). Hb levels were maintained for the remainder of the trial. Epoetin beta was very well tolerated. CONCLUSION: Epoetin beta therapy resulted in a rapid and sustained improvement in Hb levels in patients with HRPC metastatic to bone.
Subject(s)
Anemia/drug therapy , Bone Neoplasms/secondary , Erythropoietin , Erythropoietin/therapeutic use , Prostatic Neoplasms/complications , Aged , Anemia/etiology , Antineoplastic Agents, Hormonal/pharmacology , Bone Neoplasms/blood , Dose-Response Relationship, Drug , Drug Resistance, Neoplasm , Erythropoietin/adverse effects , Hemoglobins/metabolism , Humans , Male , Prospective Studies , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Recombinant ProteinsABSTRACT
Bone is the most frequent site of metastases of prostate cancer and is almost always the first and frequently the only site of metastases where disease will progress to stage D3. In addition, the number of skeletal metastatic foci is the most powerful independent prognostic factor of limited response to hormone ablation therapy and poor survival of patients with advanced prostate cancer. Furthermore, disease progression frequently occurs in the osteoblastic metastases, even though androgen ablation therapy still provides adequate and sustained control of disease at the primary site. Notably, the management of metastatic disease onto bones has traditionally relied on therapeutic modalities, which almost exclusively aim at directly inducing cancer cell death. However, accumulating pieces of evidence, from both the clinical and the basic research front, point to major limitations of this conventional approach. The in vivo response of malignant cells to anticancer therapies is directly influenced by the local microenvironment in which they metastasize. In particular, organ sites frequently involved in metastatic diseases, such as the bones, appear to confer to metastatic cells protection from anticancer drug-induced apoptosis. This protection is mediated by soluble growth factors and cytokines released by the normal cellular constituents of the host tissue microenvironment. The characterization of bone microenvironment-related survival factors has led to the development of a novel hormone manipulation which can re-introduce clinical responses in patients with stage D3 prostate cancer.
