losartan-potassium and Prostatic-Neoplasms

In this review, we discuss the effects on androgens on the haemopoietic system, focussing largely on the effects of testosterone on erythropoiesis. Stimulation of erythropoiesis is one of the most consistent effects of testosterone treatment observed in clinical trials. In men with anaemia this effect can be beneficial. Conversely, erythrocytosis is one of the most common adverse effects of testosterone treatment with a relative risk of 8.14 (95% CI: 1.87-35.40) estimated by a recent meta-analysis of randomised placebo controlled clinical trials. A reduction in haemoglobin is commonly seen in men receiving androgen deprivation therapy for prostate cancer, and in transwomen receiving gender affirming therapy to reduce serum testosterone. While mechanisms by which androgens regulate erythropoiesis are not fully understood, it is likely that effects on erythropoietic progenitor cells and erythropoietin are involved, with secondary effects on iron metabolism. In contrast, whether androgens exert clinically relevant effects on white blood cells and on platelets requires further study.

Topics: Androgen Antagonists; Androgens; Erythropoietin; Hemoglobins; Humans; Iron; Male; Prostatic Neoplasms; Testosterone

This article reviews complementary and alternative therapies for advanced prostate cancer. This is not a comprehensive survey of nontraditional therapies for prostate cancer. Rather, this review focuses on alternative and complementary therapies with published studies to evaluate efficacy and safety. Three areas are addressed: alternative forms of hormonal therapy, management of side effects of hormonal therapy, and management of skeletal complications.

Topics: Acupuncture; Adenocarcinoma; Androgen Antagonists; Androgens; Anemia; Anticarcinogenic Agents; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Breast Neoplasms; Clinical Trials, Phase II as Topic; Complementary Therapies; Depression; Diphosphonates; Drugs, Chinese Herbal; Erythropoietin; Female; Flushing; Humans; Hypericum; Male; Multicenter Studies as Topic; Neoplasms, Hormone-Dependent; Osteoporosis; Phytotherapy; Pilot Projects; Plant Extracts; Prospective Studies; Prostatic Hyperplasia; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Serenoa

Erectile dysfunction significantly impacts quality of life for men undergoing radical prostatectomy for prostate cancer. Erythropoietin is a promising neurotrophic factor for neurogenic erectile dysfunction based on preclinical and retrospective data.. ERECT (NCT00737893) is a phase 2, double-blinded, randomized, placebo-controlled trial (July 2017-December 2019) evaluating the impact of perioperative erythropoietin on recovery of erectile function and other patient-reported, health-related quality of life outcomes after bilateral nerve-sparing radical prostatectomy (3, 6, 9, and 12 months). Erythropoietin (20,000 units) or saline placebo was injected subcutaneously the day before, day of, and day after surgery for 3 total doses.. Of 63 patients assessed for eligibility, 56 patients were randomized. Arms (29 erythropoietin, 27 placebo) were well balanced (89.3% robotic, median age 55.5 years). International Index of Erectile Function-Erectile Function Domain (IIEF-EF) scores increased from median 12.5 at 3 months to 24.5 at 12 months. Median 2-week serum hemoglobin was higher for the erythropoietin arm compared to placebo (14.7 vs 13.6, p=0.02). There was no statistically significant difference in IIEF-EF scores at 6 months comparing erythropoietin to placebo (p=0.50) or at other time points (mixed model regression coefficient: -1.7, 95% CI -6.1-2.7, p=0.45). Excellent nerve-sparing rating (10/10) was associated with improved IIEF-EF recovery (+5.2, p=0.022). Other patient-reported, health-related quality of life domains as well as oncologic outcome and complications were similar between arms during followup.. In the context of brief perioperative dosing, erythropoietin did not improve recovery of erectile function for men undergoing radical prostatectomy for prostate cancer compared to placebo. Further research to identify effective adjuncts to improve health-related quality of life for these men is needed.

Topics: Double-Blind Method; Erectile Dysfunction; Erythropoietin; Humans; Male; Middle Aged; Postoperative Complications; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Quality of Life; Recovery of Function; Treatment Outcome

Erythropoietin receptors have been localized to human penile tissue and periprostatic neurovascular bundles. ERECT is a placebo-controlled, phase 2, randomized trial assessing the effect of erythropoietin on recovery of erectile function for men undergoing radical prostatectomy for prostate cancer.

Topics: Clinical Trials, Phase II as Topic; Erectile Dysfunction; Erythropoietin; Humans; Male; Postoperative Complications; Prostatectomy; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Recovery of Function

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Anemia; Castration; Double-Blind Method; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Male; Middle Aged; Prostatic Neoplasms; Quality of Life; Recombinant Proteins; Venous Thromboembolism

It was the aim of this study to prospectively study the effects on hematocrit levels, transfusion rates and quality of life (QOL) indices in men preoperatively supplemented with recombinant erythropoietin (rEPO) undergoing radical prostatectomy for clinically localized prostate cancer.. Thirty men undergoing radical prostatectomy were randomized either to receive rEPO (n=25) or to serve as controls (n=25). Outcome measurements obtained preoperatively, as well as 10 days and 6 weeks postoperatively included serum hematocrit levels, transfusion rates and QOL indices (using SF-12 validated questionnaires).. The rEPO group had a significant increase in preoperative hematocrit (median increase=4 points; p=0.002). Although there were no significant differences in hematocrit at 10 days, the rEPO had a significantly higher hematocrit value at 6 weeks (p=0.0086). No differences were observed in transfusions rates between groups (4% in each group). SF-12 mental and SF-12 physical scores were not different between the two groups at any time point.. Preoperative administration of rEPO significantly increases preoperative and postoperative hematocrit levels. However, no differences were observed with regard to transfusion rates or postoperative QOL indices despite these higher hematocrit values.

Topics: Adult; Aged; Blood Transfusion; Erythropoietin; Follow-Up Studies; Hematocrit; Humans; Male; Middle Aged; Preoperative Care; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Quality of Life; Recombinant Proteins; Treatment Outcome

Erythropoietin is shown to be an effective treatment for anemia in various types of cancers, however only limited studies have evaluated its benefits in advanced hormone-refractory prostate cancer (HRPC). This multi-center study investigated the influence of 2 different doses of epoetin beta on quality of life, hemoglobin level, need for blood transfusion, and safety, in the treatment of anemia in patients with metastatic HRPC.. This study randomized 180 patients to receive either epoetin beta 1000 IU or 5000 IU subcutaneously 3 times per week for 12 weeks. Hemoglobin was evaluated at study start and 6 time-points during the study. Quality of life (QoL) was assessed by the European Organization for Research and Treatment of Cancer questionnaire, QLC-C30, before treatment start and after 6 and 12 weeks of treatment. Best supportive care and blood transfusions were given, if clinically indicated. Additional laboratory values and adverse events were followed for safety.. Hemoglobin increased significantly (>20 g/l) in 43% in the high dose (HD) group and 25% in the low dose (LD) group in response to treatment. Levels were significantly higher in the HD group than the LD group (p < 0.001) after 8 and 12 weeks. QoL improved significantly if the increase in hemoglobin was >20 g/l. Significantly more patients in the LD group received blood transfusions than the HD group (p < 0.005). There were no differences between the groups regarding overall quality of life and fatigue. The treatment was well tolerated in both groups.. Epoetin beta is shown to be safe and effective for the treatment of anemia in many patients with HRPC. It is found to improve QoL and physical functioning, and relieve fatigue symptoms, in many of these critically ill patients.

Topics: Aged; Anemia; Blood Transfusion; Erythropoietin; Hemoglobins; Humans; Male; Prostatic Neoplasms; Quality of Life; Recombinant Proteins

All patients in the first group tolerated sampling of four transfusion units of autologous blood in the course of two weeks with subsequent erythropoietin administration very well. Erythropoietin was well tolerated, no local nor systemic undesirable side-effects or complications were observed. The mean transferrin and serum iron values remained during sampling of autotransfusions and erythropoietin administration within the range of normal values reported by our laboratory. The ferritin levels were above the norm. On the other hand in patients of the control group it was not possible--due to the decline of haemogram values--to sample in 45% the required amount of autologous blood before operation. For the same reason it was not possible to implement haemodilution as required. In similar blood losses administration of allogenic blood was necessary in 35% patients of the control group whereby in the group of patients with erythropoietin allogenic blood was administered in two cases (10%). Erythropoietin administration can effectively facilitate preoperative sampling of autotransfusion within a relatively short period. By its administration we can prevent a marked decline of red blood cells as a result of sampling of several preserves of autologous blood at a rapid rate. A satisfactory value of the haematocrit before the operation proper moreover makes it possible to collect a larger amount of blood in case of acute isovolaemic haemodilution. This enhances the patient's safety in relation to risks ensuing from administration of allogenic blood.

Topics: Blood Loss, Surgical; Blood Transfusion, Autologous; Carcinoma; Erythropoietin; Hematocrit; Hemodilution; Humans; Male; Preoperative Care; Prostatectomy; Prostatic Neoplasms

The safety and effects on hematocrit of recombinant human erythropoietin (epoetin alfa) were evaluated in men undergoing radical retropubic prostatectomy.. Between February 1, 1997 and November 2, 1998, 305 men with clinically localized adenocarcinoma of the prostate underwent radical retropubic prostatectomy performed by a single surgeon (H. L.). Of these men 283 with a baseline hematocrit of less than 48% received 600 IU/kg. epoetin alfa 14 days (-14) and 7 days (-7) before radical retropubic prostatectomy. Hematocrit was measured at baseline on day -14, on day -7, just before anesthesia induction on day 0, immediately postoperatively and on the day of discharge home. The number of allogeneic units transfused, and all intraoperative and postoperative complications were recorded.. Mean hematocrit at baseline on day -14 and at induction on day 0 was 42.9% and 45.8%, respectively (p = 0.0001). The frequency of hematocrit decreasing, showing no change or increasing 0.1 to 1.9, 2.0 to 3.9 or greater than 4.0 hematocrit points was 16.5%, 0.5%, 23%, 22% and 38%, respectively. Of the men 17% had no increase in hematocrit. A weak correlation existed between baseline hematocrit and the erythropoietic response to epoetin alfa (r2 = 0.06). Mean change in hematocrit after treatment with epoetin alfa in the quartile baseline hematocrit groups 34.2 to 41.4, 41.5 to 43.2, 43.3 to 44.9 and 45.0 to 48.0 hematocrit points was 3.71, 2.45, 3.86 and 1.02 hematocrit points, respectively. Of the surgical candidates 22 (9.1%) achieved an induction hematocrit of greater than 51%. Of the 283 men receiving epoetin alfa 21 (7.4%) also received an allogeneic transfusion. The transfusion rate did not correlate with induction hematocrit. The only adverse cardiovascular event was an uncomplicated postoperative pulmonary embolus.. Our prospective study demonstrates that epoetin alfa given preoperatively in 2 doses of 600 IU/kg. is safe for significantly increasing hematocrit in men before radical retropubic prostatectomy. It is intuitive that the significant increase in hematocrit decreases the requirement for allogeneic blood transfusion.

Topics: Adenocarcinoma; Blood Loss, Surgical; Epoetin Alfa; Erythropoietin; Hematinics; Hematocrit; Humans; Male; Middle Aged; Preoperative Care; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Recombinant Proteins

The usefulness of recombinant human erythropoietin (rHuEPO) on autologous blood transfusion was investigated in 18 patients undergoing radical prostatectomy (mean age 67.4 years). A total of 800 ml blood was deposited by two donations of 400 ml each, concomitant with subcutaneous administration of 24,000 U rHuEPO at each donation. All patients completed two successive donations with no adverse effects. The mean hemoglobin concentration was 13.7 g/dl before the donation and 13.0 g/dl on the day of operation. The decrease in hemoglobin was effectively prevented in 12 patients (66.7%) with rHuEPO, when compared with the predicted decrease in the absence of recovery from anemia. During radical prostatectomy, no homologous blood transfusion was required in 16 of 18 patients (88.9%). In conclusion, predeposit autologous blood transfusion with rHuEPO is useful for diminishing the risks associated with homologous blood transfusions.

Topics: Aged; Anemia; Blood Transfusion, Autologous; Erythropoietin; Hemoglobins; Humans; Male; Middle Aged; Prostatectomy; Prostatic Neoplasms; Recombinant Proteins

To determine the efficacy and safety of subcutaneous administration of recombinant human erythropoietin (r-HuEPO) at a dose of 200 units/kg/day to cancer patients undergoing radiotherapy.. This is a randomized, open-labeled, Phase II study. Only patients receiving radiotherapy +/- chemotherapy are included. Eligibility is restricted to patients with lung cancer, carcinoma of the uterine cervix, prostatic adenocarcinoma, or adenocarcinoma of the breast. Patients in the control and treatment arms receive radiotherapy with similar policies, and their doses of radiotherapy and treatment volumes are determined by the site and stage of the disease. Patients in the "treatment arm" receive 200 units/kg/day of r-HuEPO, subcutaneously, five times a week with iron (Fe SO4, 325 mg. p.o., t.i.d.) supplements. Complete blood counts are obtained weekly. Quality of life is assessed weekly by the patients themselves by a few simple entries on an analog scale.. Twenty-six patients have been entered in the study so far. Twelve patients were placed in the control arm and 14 in the treatment arm. Pre-randomization demographic and laboratory mean values in both arms were comparable, with none of 16 parameters compared reaching statistical significance. Our results can be summarized as follows: (a) Mean hemoglobin, hematocrit, and red blood cell values increased gradually in the treatment arm patients. Week-by-week comparison showed that mean values for these three parameters were significantly higher in the treatment arm than in the control arm. For example, the p values for the differences in hemoglobin mean values for weeks 1-6 were 0.015, 0.002, 0.003, 0.0002, 0.0006, and 0.007, respectively. Similar trends were observed for red blood cells and the hematocrit values. (b) No significant toxicity has been encountered. (c) No significant differences in the mean values of white blood cells and platelet counts were seen between the two arms. The values of these two parameters declined over the course of radiotherapy. (d) The mean weekly increase in hemoglobin levels in the treatment arm was 0.43 gm/dl.. (a) The safety and efficacy of r-HuEPO, with 200 units/kg/day of subcutaneous administration, have been confirmed in our study group. (b) However, the rate of increase in hemoglobin levels is not very rapid with the doses used. (c) Dose escalation studies are needed for determination of the feasibility of improving hemoglobin levels by about 1 gm/dl/week. (d) The question whether improvement in hemoglobin with r-HuEPO therapy can improve outcome by improving tumor oxygenation needs to be studied in carcinoma of the uterine cervix and squamous cell carcinoma of the head and neck.

Topics: Adenocarcinoma; Anemia; Breast Neoplasms; Combined Modality Therapy; Erythropoietin; Female; Humans; Injections, Subcutaneous; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Recombinant Proteins

Prostate cancer (PCa) is the most prevalent cancer in U.S. men and many other countries. Although primary PCa can be controlled with surgery or radiation, treatment options of preventing metastatic PCa are still limited. To develop a new treatment of eradicating metastatic PCa, we have created an injectable cancer trap that can actively recruit cancer cells in bloodstream. The cancer trap is composed of hyaluronic acid microparticles that have good cell and tissue compatibility and can extend the release of chemokines to 4 days in vitro. We find that erythropoietin (EPO) and stromal derived factor-1α can attract PCa in vitro. Animal results show that EPO-releasing cancer trap attracted large number of circulating PCa and significantly reduced cancer spreading to other organs compared with controls. These results support that cancer trap may serve as a unique device to sequester circulating PCa cells and subsequently reduce distant metastasis.

Topics: Chemokine CXCL12; Chemokines; Erythropoietin; Humans; Hyaluronic Acid; Male; Neoplasm Metastasis; Neoplastic Cells, Circulating; Prostatic Neoplasms

The erythropoietin-producing hepatoma A2 receptor (EphA2) is a tyrosine kinase overexpressed by tumor stroma and cancer cells. A high expression level of EphA2 predicts poor prognosis, correlating with disease progression and metastasis. Therefore, EphA2 is a relevant therapeutic target for human cancer. Antibodies, selectively bound to EphA2, can induce rapid receptor phosphorylation that results in antibody internalization and degradation. This internalization mechanism has been exploited with the development of antibody-drug conjugates (ADCs) for cancer chemotherapy. In this study, we used PET imaging to study the pharmacokinetics and tumor delivery of a panel of anti-EphA2 monoclonal antibodies (mAbs) with and without drug conjugates.

Topics: Antibodies, Monoclonal; Cell Line, Tumor; Cell Survival; Chelating Agents; Drug Delivery Systems; Ephrin-A2; Epitopes; Erythropoietin; Humans; Immunoconjugates; Male; Positron-Emission Tomography; Prostatic Neoplasms; Radioisotopes; Receptor, EphA2; Zirconium

Erythropoietin (Epo) is used in clinical settings to enhance hematopoietic function and to improve the quality of life for patients undergoing chemotherapy by reducing fatigue and the need for transfusions. However, several meta-analyses have revealed that Epo treatments are associated with an increased risk of mortality in cancer patients. In this study, we examined the role of Epo in prostate cancer (PCa) progression, using in vitro cell culture systems and in vivo bone metastatic assays. We found that Epo did not stimulate the proliferation of PCa cell lines, but did protect PCa cells from apoptosis. In animal models of PCa metastasis, no evidence was found to support the hypothesis that Epo enhances metastasis. Together, these findings suggest that Epo may be useful for treating severe anemia in PCa patients without increasing metastatic risk.

Topics: Animals; Apoptosis; Blotting, Western; Bone Neoplasms; Cell Line, Tumor; Cell Proliferation; Erythropoietin; Flow Cytometry; Humans; Male; Mice; Mice, SCID; Neoplasm Metastasis; Prostatic Neoplasms

The effect of erythropoietin stimulation on bone marrow uptake of FDG has been well documented. Similar metabolic activation of bone marrow with (18)F-fluorocholine (FCH) has not been previously reported. FCH PET/CT was performed in a patient with biochemical recurrent prostate cancer who was receiving erythropoietin for hemochromatosis. Diffuse skeletal uptake of FCH was seen. (18)F-Fluoride PET/CT performed the following day demonstrates multiple abnormal focal bone metastases. Generalized skeletal uptake of FCH results in poor contrast between the metastases compared to noninvolved bone. The metabolic activation of bone marrow by erythropoietin could result in false-negative FCH results for detecting bone metastases.

Topics: Aged; Biological Transport; Bone Marrow; Choline; Erythropoietin; Fluorides; Fluorine Radioisotopes; Humans; Male; Multimodal Imaging; Positron-Emission Tomography; Prostatic Neoplasms; Tomography, X-Ray Computed

To examine the impact of short-term preoperative utilization of erythropoietin-stimulating agents (ESAs) on biochemical recurrence (BCR)-free survival rates after open radical retropubic prostatectomy (ORRP) in light of the fact that the risk/benefit of ESAs has recently been questioned by the Food and Drug Administration (FDA) after reports showing a decreased survival.. From 2000 to 2008, 1567 patients underwent ORRP and 97.5% of these signed informed consent to participate in the New York University Prospective and Longitudinal Outcomes Study. Of the remaining 1528 patients, 1317 (86%) received preoperative ESA (group 1) and 211 (14%) did not (group 2). Patients were also classified as having low-, intermediate- or high-risk disease based on D'Amico risk categories. Kaplan-Meier survival curves and Cox's proportional hazard models were used to estimate BCR-free survival by ESA treatment.. A significant difference was observed for BCR-free survival between the low- and intermediate/high-risk groups. There were no statistically significant differences between groups 1 and 2 for BCR-free survival in the entire study populations and within risk groups. In addition, Cox regression models showed no statistically significant differences in BCR-free survival according to preoperative ESA administration in the entire cohort as well as among the low- and intermediate/high-risk groups.. The short-term use of ESAs as a preoperative blood management strategy for patients undergoing ORRP has no clinically relevant adverse effects on the biology of prostate cancer. The present study supports the use of these agents before the procedure in patients undergoing surgery for localized disease.

Topics: Aged; Antineoplastic Agents, Hormonal; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Kaplan-Meier Estimate; Longitudinal Studies; Male; Middle Aged; Neoplasm Recurrence, Local; Preoperative Care; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Recombinant Proteins

To critically examine the cardiovascular and thromboembolic risks associated with erythropoietin stimulating proteins (ESPs) in men with normal hemoglobin levels undergoing open radical retropubic prostatectomy.. Between October 1, 2000, through December 31, 2006, a total of 1308 men underwent open radial retropubic prostatectomy by a single surgeon. Of these men, 1095 received preoperative ESPs. Hematocrit levels measured at baseline, immediately before anesthesia induction and at hospital discharge, were prospectively entered into a database. Thromboembolic and cardiovascular complications were prospectively captured during the hospitalization and after surgery.. The mean Delta preoperative hematocrit level was 5.9 g/dL. The pre-anesthesia induction hematocrit level was 49.2%. Hospital discharge hematocrit level was 33.6 g/dL. The overall risk of cardiovascular and thromboembolic complications in men receiving ESP were 0.55% and 0.45%, respectively. The risk of cardiovascular and thromboembolic complications were independent of the Delta in preoperative hematocrit or the absolute level of the pre-anesthesia induction hematocrit.. ESPs represent a safe and effective preoperative blood management strategy for men undergoing open radical retropubic prostatectomy.

Topics: Aged; Analysis of Variance; Cardiovascular Diseases; Cohort Studies; Erythropoietin; Follow-Up Studies; Hematocrit; Hemoglobins; Humans; Male; Middle Aged; Postoperative Complications; Preoperative Care; Prospective Studies; Prostatectomy; Prostatic Neoplasms; Recombinant Proteins; Risk Assessment; Survival Rate; Thromboembolism; Treatment Outcome

Topics: Anemia; Cardiovascular Diseases; Erythropoietin; Humans; Male; Postoperative Complications; Preoperative Care; Prognosis; Prostatectomy; Prostatic Neoplasms; Recombinant Proteins; Risk Assessment; Survival Analysis; Thromboembolism

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Anemia; Antineoplastic Agents, Hormonal; Erythrocyte Count; Erythropoiesis; Erythropoietin; Humans; Insulin-Like Growth Factor I; Male; Middle Aged; Prostatic Neoplasms; Receptor, IGF Type 1; Recombinant Proteins; Testosterone

Erythropoietin receptors have been identified on a variety of cancer-derived cell lines and primary cancer cells, including those of prostate cancer. The functional status of these extrahematopoietic erythropoietin receptors remains a matter of some dispute. The publication of several important clinical trials suggesting a direct effect of erythropoietin on the growth and survival of primary tumors adds further importance to the question of whether erythropoietin receptors on cancer cells are functional. We have reported previously that human prostate cancer cell lines and primary prostate cancer cells express functional erythropoietin receptors that respond to exogenous erythropoietin by increased cell proliferation and STAT5 phosphorylation. We now show that prostate cancer cell lines express both the EPO gene and the biologically active erythropoietin. The coexpression of functional receptor and biologically active ligand in the cells has led us to hypothesize an autocrine/paracrine mechanism, driven by endogenous erythropoietin, which may modulate the growth and progression of prostate cancer. To test our hypothesis, we have knocked down, independently, erythropoietin receptor and erythropoietin on prostate cancer cells by transfection with short hairpin RNAs. Erythropoietin receptor knockdown cells grow significantly more slowly than their erythropoietin receptor-bearing counterparts in monolayer culture, produce fewer, smaller colonies in soft agar, and do not exhibit erythropoietin-induced signaling. Erythropoietin knockdown cells exhibit dramatically slower rates of growth, which could be restored by transfecting the cells with a murine erythropoietin gene. Taken together, our data suggest that the coordinated regulation of a functional erythropoietin/erythropoietin receptor axis in prostate cancer cells may be integral to the growth and progression of prostate cancer.

Topics: Cell Adhesion; Cell Growth Processes; Cell Line, Tumor; Cell Survival; Down-Regulation; Erythropoietin; Gene Knockdown Techniques; Humans; Male; Prostatic Neoplasms; Receptors, Erythropoietin; RNA, Messenger; Signal Transduction

Anemia is a common morbidity of advanced prostate cancer, and prostate cancer treatment and has been associated with a worse overall survival and reduced quality of life in patients with prostate cancer. We sought to determine if infrequent dosing of darbepoetin alfa is safe and effective in treating anemia in patients receiving systemic therapy for prostate cancer.. Sixteen patients with histologically confirmed prostate cancer with bone metastases on androgen deprivation therapy with or without chemotherapy; and a baseline hemoglobin (Hb) < or = 12 g/dL (amended to < or = 11 g/dL) were enrolled. The primary endpoints were the proportion of patients who had a baseline Hb > or = 12.5 g/dL and the proportion whose baseline Hb increased by > or = 1 g/dL. Patients were initially treated with 300 microg of darbepoetin alfa every 4 weeks. The dose was increased to 500 microg, 800 microg, and 1000 microg at each subsequent visit if the baseline Hb was not at target and had not increased by > or = 1 g/dL during the previous 4 weeks. Treatment was planned for 6 months.. Treatment was well tolerated with no grade > or = 3 toxicities. Fourteen patients were assessable. The median Hb at study entry was 10.7 g/dL (range, 8.4-12). Serum Hb increased by > or = 1 g/dL in 10 patients (71%; 95% confidence interval, 42%-92%) and 7 patients (50%; 95% confidence interval, 23%-77%) reached an Hb of > or = 12.5 g/dL after treatment with doses that ranged from 300 microg to 1000 microg.. Darbepoetin alfa administration every 4 weeks is feasible and well tolerated. Target Hb increases were achieved in approximately half of the patients and required doses that ranged from 300 microg to 1000 microg.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Bone Neoplasms; Darbepoetin alfa; Erythropoietin; Feasibility Studies; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Prostatic Neoplasms

Erythropoietin (Epo), the principal regulator of erythroid progenitor survival, growth, and differentiation, initiates its action by binding to its cognate cell surface receptor (EpoR). EpoR have been identified on a variety of non-hematopoietic cells, both normal and malignant, however, little is known about the function of EpoR on malignant cells.. RT-PCR, Western blotting, and immunohistochemistry were used to demonstrate that prostate cancer cells express EpoR at both the gene and protein level. Cell proliferation assays and STAT5 phosphorylation were used to demonstrate Epo's mitogenic action and intracellular signaling, respectively.. We have demonstrated that transformed prostate epithelial and prostate cancer cell lines, as well as primary prostate tissue, express the EpoR. Importantly, the EpoR on prostate cells are functional, as demonstrated by the observation that each of the cell lines exhibited a dose-dependent proliferative response to Epo, and that Epo triggered STAT5b phosphorylation in the cells.. Human prostatic epithelial cells and prostate cancer cells express functional EpoR, and Epo serves as a growth factor for these cells. These results have implications for our understanding of normal prostatic growth and development and of the pathobiology of human prostate cancer.

Topics: Blotting, Western; Cell Line, Transformed; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; Epithelial Cells; Erythropoietin; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Male; Phosphorylation; Prostate; Prostatic Neoplasms; Receptors, Erythropoietin; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; STAT5 Transcription Factor

Topics: Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Confidence Intervals; Disease Progression; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Male; Odds Ratio; Ovarian Neoplasms; Prostatic Neoplasms; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Analysis; Therapeutic Equivalency; Treatment Outcome

Erythropoietin is a hematopoietic cytokine that regulates the production of red blood cells. Erythropoietin is normally produced in the adult kidney in a hypoxia-inducible manner. The recombinant form of human erythropoietin is in clinical use for the prevention and treatment of anemia that is associated with cancer and its treatment with chemoradiation therapy. A series of recent studies from our laboratory and others have reported the expression of receptors for erythropoietin in several different types of human cancer cells. In the present study, we investigated the expression of erythropoietin receptor and its ligand erythropoietin in human prostate cancer. In clinical specimens of prostate cancer, we found abundant expression of erythropoietin receptor protein in all primary tumors examined using immunohistochemistry. Furthermore, we observed erythropoietin coexpression in prostate cancer cells by immunohistochemical analysis. To determine whether monolayer cultures of continuous cell lines derived from prostate cancer also express erythropoietin receptor and erythropoietin, we studied well-characterized hormone-responsive (LNCaP) and hormone-refractory (PC-3) prostate cancer cell lines. We performed reverse-transcription and polymerase chain reaction assays to detect erythropoietin receptor and erythropoietin mRNA transcripts, and also immunoprecipitation and immunoblotting to detect erythropoietin receptor protein expression in prostate cancer cells. These experiments revealed the expression of both erythropoietin receptor and erythropoietin in LNCaP and PC-3 cells suggesting that these prostate cancer cell lines may serve as useful experimental models for further studies of erythropoietin and erythropoietin receptor function in prostate cancer. The coexpression of erythropoietin receptor and its ligand erythropoietin in human prostate cancer cells suggests the potential for growth regulation by erythropoietin-erythropoietin receptor in an autocrine or paracrine manner.

Topics: Animals; Blotting, Western; Cell Line, Tumor; CHO Cells; Cricetinae; Cricetulus; Erythropoietin; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Male; Prostatic Neoplasms; Receptors, Erythropoietin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

There is a high incidence of anemia in patients with advanced prostate cancer (PC) under androgen deprivation. Pathophysiology of this anemia remains unclear. Erythropoietin (EPO) is the main growth factor inducing erythropoesis in response to hypoxia. In this study, function of the EPO-system following androgen deprivation was tested in standardized animal model.. Animals were pretreated by either orchiectomy, injection of cyproteroneacetate or flutamide. After hypoxic stimulation, EPO mRNA expression and EPO serum levels were studied.. In all animals, EPO mRNA expression and EPO serum levels were increased following hypoxic stimulation. Compared to the control group, this increase was even more pronounced after androgen deprivation. None of the different forms of androgen deprivation had a negative stimulating effect on EPO expression.. Unexpectedly, androgen deprivation did not suppress EPO mRNA expression and EPO serum concentrations. Instead, stimulation of the EPO system was even more pronounced after androgen deprivation. A deficient EPO system does not appear to contribute to the clinically observed anemia in patients treated by androgen deprivation.

Topics: Androgen Antagonists; Androgens; Anemia; Animals; Cyproterone Acetate; Erythropoietin; Flutamide; Hematopoiesis; Humans; Male; Orchiectomy; Prostatic Neoplasms; Rats; Rats, Wistar

Homeostasis under hypoxic conditions is maintained through a coordinated transcriptional response mediated by the hypoxia-inducible factor (HIF) pathway and requires coactivation by the CBP and p300 transcriptional coactivators. Through a target-based high-throughput screen, we identified chetomin as a disrupter of HIF binding to p300. At a molecular level, chetomin disrupts the structure of the CH1 domain of p300 and precludes its interaction with HIF, thereby attenuating hypoxia-inducible transcription. Systemic administration of chetomin inhibited hypoxia-inducible transcription within tumors and inhibited tumor growth. These results demonstrate a therapeutic window for pharmacological attenuation of HIF activity and further establish the feasibility of disrupting a signal transduction pathway by targeting the function of a transcriptional coactivator with a small molecule.

Topics: Animals; Anti-Bacterial Agents; Aryl Hydrocarbon Receptor Nuclear Translocator; Carcinoma, Hepatocellular; Cell Hypoxia; Colonic Neoplasms; Disulfides; DNA-Binding Proteins; E1A-Associated p300 Protein; Erythropoietin; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Indole Alkaloids; Liver Neoplasms; Luciferases; Male; Mice; Mice, Nude; Nuclear Proteins; Prostatic Neoplasms; Protein Binding; Receptors, Aryl Hydrocarbon; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Trans-Activators; Transcription Factors; Transcription, Genetic; Transplantation, Heterologous; Vascular Endothelial Growth Factor A

Topics: Apoptosis; Cell Hypoxia; Erythropoietin; Humans; Male; Neovascularization, Pathologic; Prostate; Prostatic Neoplasms; Receptors, Erythropoietin

Radical retropubic prostatectomy (RRP) has resulted in substantial blood loss and the frequent need for homologous blood transfusion. In this study, the efficacy of autologous blood transfusion, from medical and financial perspectives, was evaluated in patients undergoing RRP.. Between 1994 and 2000, 80 patients with localized prostate cancer underwent RRP in our institute. Based on informed consent, preoperative donation of autologous blood (PDA) was performed in 65 out of 80 patienets. Four or six units were donated during the first 3 years; however, donation units were reduced to a maximum of 4 units since 1997 onwards. The discard rate of donated blood and frequency of homologous transfusion were examined. Changes of hematocrit (Ht) and hemoglobin (Hb) levels through donation and surgery and important factors that may affect postoperative levels of Ht and Hb were evaluated in 56 patients receiving 4-unit donations.. Overall, 2 or 4 units of donated blood were discarded in four patients and homologous transfusion was required in two patients. In 56 patients receiving 4-unit donation, the mean Ht level at predonation was 43.3%. Following donation, this decreased to 35.7%. The administration of recombinant human erythropoietin (rHuEpo) relieved declining Ht levels following donation, but changes in Ht levels after surgery were minor. Important factors related to postoperative decline of Ht and Hb levels were operative time and blood loss.. The program of 4-unit PDA can be performed safely without rHuEpo injection, and it is useful to reduce the risk of requiring homologous transfusion. However, more efficient programs to relieve patient burden and to reduce medical cost are needed.

Topics: Aged; Blood Loss, Surgical; Blood Transfusion, Autologous; Erythropoietin; Hematocrit; Hemoglobins; Humans; Male; Middle Aged; Prostatectomy; Prostatic Neoplasms; Recombinant Proteins

Nine patients with hormone-refractory metastatic prostatic adenocarcinoma and anemia were treated with recombinant human erythropoietin (rHuEpo) at a median dose of 150 U/kg BW 3 times a week subcutaneously. Baseline hemoglobin (Hb) ranged from 70 to 116 g/L, and the study duration was 12 weeks (median patient participation period was 8 weeks).. Four patients demonstrated a median Hb increase of 20 g/L and were considered responders. Three patients showed a median increase of 17 g/L but required blood transfusion once, and were therefore considered as partial responders. Baseline erythropoietic status showed a significant correlation between serum Epo and Hb. Inadequate Epo production, evaluated by the observed/predicted log Epo ratio, was found in two patients. Defective bone marrow activity, demonstrated by low transferrin receptor (TfR), and hypoferremia in spite of abundant iron stores were also shown. Hemorheological investigations showed elevated plasma viscosity.. Our results indicate that suppression of erythropoiesis can be mainly explained by the depressed marrow activity. The altered hemorheology might contribute to the anemia. This anemia could possibly be corrected with rHuEpo.

Topics: Adenocarcinoma; Aged; Anemia; Blood Transfusion; Blood Viscosity; Bone Marrow; Erythropoietin; Hemoglobins; Humans; Iron; Male; Middle Aged; Prostatic Neoplasms; Receptors, Transferrin; Recombinant Proteins; Transferrin

In rats with Mat Lylu prostatic carcinoma, significant changes in blood composition and red blood cell (RBC) characteristics were observed. Anaemia, characterised by a decrease in the number of RBC and the reduction of haemoglobin and the iron content in plasma, was correlated with tumour size and the accumulation of spermidine and spermine in the RBC. In large tumours, spermidine levels were increased by 8-fold over normal value. Spleen weight and splenic spermidine concentrations were enhanced in animals with tumours. After splenectomy, the rate of tumour growth decreased by 30%. It is proposed that anaemia in tumour-bearing animals is caused by enhanced RBC lysis, owing to the alteration of the rheological properties of RBC. These may be caused by the alterated surface characteristics due to polyamine accumulation. RBC lysis and high concentrations of polyamines in RBC and spleen appear, not only to favour tumour growth, but also to compromise the immunological defence mechanisms against neoplastic invasion.

Topics: Anemia; Animals; Erythrocyte Count; Erythrocytes; Erythropoietin; Iron; Male; Neoplasm Transplantation; Paraneoplastic Syndromes; Polyamines; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Spleen; Urea

We have reviewed the incidence of cisplatin-induced anaemia in patients affected with solid tumours treated with at least three courses of first-line cisplatin-containing regimens. In our experience, a low percentage (5%) of patients required transfusions of red blood cells. We think it is of the utmost importance to adopt uniform criteria in monitoring and treatment of patients at risk of developing cisplatin anaemia and to identify subsets of patients to eventually treat with erythropoietin.

Topics: Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Erythrocyte Transfusion; Erythropoietin; Evaluation Studies as Topic; Female; Humans; Incidence; Lung Neoplasms; Male; Ovarian Neoplasms; Prostatic Neoplasms; Retrospective Studies; Risk Factors

In order to reduce the rate of homologous blood transfusion, predeposit autologous blood transfusion has been introduced in 134 out of 266 patients undergoing transurethral resection of the prostate since February 1988. Nine (6.7%) out of 134 patients who deposited their own blood were also transfused with homologous blood. In contrast, the rate of homologous blood transfusion was 22.7% in 132 patients who did not deposit autologous blood. Overall homologous blood transfusion rate (14.7%) in the past 4.5 years has been much lower than in the previous 4 years (22.2% in 203 patients). In 6 patients in whom blood donation was performed concurrently with administration of recombinant human erythropoietin, decrease of haemoglobin level was significantly less than in those without rHuEPO. Predeposit autologous blood transfusion can reduce homologous blood transfusion rate. It is safe and easily performed, and more effective when combined with rHuEPO administration even in elderly patients undergoing TURP.

Topics: Aged; Aged, 80 and over; Blood Banks; Blood Transfusion; Blood Transfusion, Autologous; Erythropoietin; Hemoglobins; Humans; Intraoperative Care; Male; Middle Aged; Preoperative Care; Prostatic Hyperplasia; Prostatic Neoplasms; Recombinant Proteins; Retrospective Studies; Surgical Procedures, Operative; Urethra

Topics: Acid Phosphatase; Alkaline Phosphatase; alpha 1-Antitrypsin; alpha-Fetoproteins; Antibodies, Neoplasm; Antigens, Neoplasm; Carcinoembryonic Antigen; Chorionic Gonadotropin; Erythropoietin; Estrone; Female; Hormones, Ectopic; Humans; Inclusion Bodies, Viral; Isoenzymes; Kidney Neoplasms; L-Lactate Dehydrogenase; Male; Placental Lactogen; Polyamines; Prostatic Neoplasms; Receptors, Cell Surface; Sex Hormone-Binding Globulin; Testicular Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms

Topics: Anemia; Anemia, Aplastic; Anemia, Sickle Cell; Animals; Biological Assay; Breast Neoplasms; Cachexia; Erythrocytes; Erythropoiesis; Erythropoietin; Iron; Iron Isotopes; Leukemia; Lymphoma; Male; Mice; Plasma; Polycythemia; Prostatic Neoplasms

Topics: Adrenal Glands; Adrenalectomy; Animals; Breast Neoplasms; Erythropoietin; Female; Humans; Hypophysectomy; Male; Mice; Pituitary Gland; Prostatic Neoplasms

Topics: Blood Chemical Analysis; Epoetin Alfa; Erythropoietin; Geriatrics; Humans; Male; Prostatectomy; Prostatic Neoplasms