losartan-potassium and Bone-Neoplasms

The Breast Cancer-Anemia and the Value of Erythropoietin (BRAVE) study evaluated whether epoetin beta would improve survival in patients with metastatic breast cancer (MBC).. BRAVE was an open-label, randomized, multicenter study in patients with MBC treated with anthracycline- and/or taxane-based chemotherapy. Patients (hemoglobin [Hb] < 12.9 g/dL) were randomly assigned (1:1) to epoetin beta 30,000 U subcutaneously once weekly or control for 24 weeks. The primary efficacy variable was overall survival. Secondary efficacy outcomes included progression-free survival, transfusion- and severe anemia-free survival, Hb response, safety, and quality of life (QoL).. After 18 months of follow-up, 62 (27%) of 231 patients survived with epoetin beta therapy and 63 (27%) of 232 with control. No difference was detected in overall survival (hazard ratio [HR] = 1.07; 95% CI, 0.87 to 1.33, P = .522) or progression-free survival (HR = 1.07; 95% CI, 0.89 to 1.30, P = .448). There was a statistically significant benefit on transfusion- and severe anemia-free survival compared with control (HR = 0.59; P = .0097). Median Hb level increased with epoetin beta (11.7 g/dL at baseline to 13.3 g/dL at 24 weeks) but did not change with control (11.5 v 11.4 g/dL). Patients receiving epoetin beta experienced more thromboembolic events (TEEs) compared with controls (13% v 6%; P = .012) with no difference in serious TEEs (4% v 3%). Epoetin beta did not significantly improve QoL in this study where patients had a high baseline Hb value.. In patients with MBC receiving chemotherapy and initial Hb less than 12.9 g/dL, epoetin beta increased Hb. No difference was detected in overall survival. Because of its superiority design, this study cannot, however, exclude clinically important differences in survival with absolute certainty.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Disease Progression; Disease-Free Survival; Drug Administration Schedule; Erythropoietin; Female; Hemoglobins; Humans; Injections, Subcutaneous; Lymphatic Metastasis; Middle Aged; Quality of Life; Recombinant Proteins; Survival Rate; Taxoids

The combination of interferon-alpha2a (IFN-alpha2a) and interleukin-2 (IL-2) induces objective responses in patients with metastatic renal cell carcinoma (MRCC). Anaemia is associated with poor cancer control and reduced quality of life. The aim of the study was to investigate response rate and quality of life in patients with MRCC receiving the combination of Erythropoetin, IFN-alpha2a and IL-2.. Patients with MRCC received epoetin beta (150 IU/kg and haemoglobin <130 g/l or 75 IU/kg and haemoglobin >or=130 g/l) three times weekly, from 14 days before and continuing throughout immunotherapy. In weeks 3-6 the patients received IFN-alpha2a 6 x 10(6) IU/m2 and IL-2 4.5 x 10(6) IU/m2 three times weekly on days 1, 3 and 5. The treatment was repeated two times and in the case of success a third cycle was added. The quality of life was assessed with the FACT questionnaire for fatigue, before, during and after therapy.. A total of 21 patients were treated, 19 of whom could be evaluated concerning response, toxicity and quality of life. We observed 1 complete remission, 2 partial remissions, 5 cases of stable disease and 11 with progressive disease. The overall response rate was 16%. Toxicity was mild to moderate; there were no WHO grade III or IV toxicity. The quality of life increased in ten patients, nine of whom exhibited an increase in their haemoglobin during therapy. Five of the nine patients with decreased quality of life also experienced a decrease in their haemoglobin. The correlation of increased haemoglobin and quality of life was significant (p<0.05).. The combination of IFN-alpha2a, IL-2 and epoetin beta resulted in objective remissions with mild to moderate toxicity. The quality of life correlates significantly with increasing haemoglobin.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma, Renal Cell; Chemotherapy, Adjuvant; Combined Modality Therapy; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Female; Follow-Up Studies; Hemoglobinometry; Humans; Injections, Subcutaneous; Interferon alpha-2; Interferon-alpha; Interleukin-2; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Nephrectomy; Quality of Life; Recombinant Proteins

Epoetin alfa (EPO, PROCRIT) pharmacokinetics and pharmacodynamics were evaluated in children with malignant solid tumors receiving chemotherapy.. Children initially received IV EPO 600 IU/kg (max dose 40,000 IU) or placebo once weekly for 16 weeks. Dose was increased to 900 IU/kg (max dose 60,000 IU) for patients not achieving a 1 g/dl increase in hemoglobin by study week 3 or 4. Serial PK samples were collected for 24 hr after the first study dose, and after the 10th or 11th dose. Serum EPO concentrations were analyzed using an ELISA assay, and pharmacokinetics were evaluated using compartmental methods.. Twelve children participated; six (median age 15.2 years; range 9.3-18.6 years) were randomized to receive EPO. All children required dosage increases to 900 IU/kg due to no response. The median (range) apparent EPO AUC0-24 and clearance (CL) were 67.1 IU/ml.hr (13.8-102.6) and 0.26 L/hr/m2 (0.19-1.08), respectively. After the 10th or 11th EPO dose in four of these six EPO patients, the median (range) apparent AUC0-24 and CL of EPO was 126.5 IU/ml.hr (107.3-161.1) and 0.21 L/hr/m2 (0.15-0.25), respectively. No significant correlations were observed between pharmacokinetic parameters and pharmacodynamic effects.. EPO disposition in our patients was similar to other pediatric patient populations or adults receiving IV EPO. Interesting but insignificant trends were noted in pharmacodynamic effects.

Topics: Adolescent; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Child; Chondrosarcoma; Dose-Response Relationship, Drug; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Injections, Intravenous; Male; Melanoma; Osteosarcoma; Placebos; Recombinant Proteins; Skin Neoplasms; Time Factors; Treatment Outcome

Patients undergoing chemotherapy for treatment of malignancy frequently experience clinically significant anemia. Myelosuppressive chemotherapy impairs erythropoiesis, which may not fully recover between treatment cycles. Recombinant human erythropoietin (rHuEPO) has been effectively introduced in anemic patients suffering from chronic renal failure. The present study was designed to assess, first, whether rHuEPO treatment decreases transfusion requirements in chemotherapy-induced anemia and, second, whether high-dose rHuEPO application is safe.. Thirty consecutive anemic patients (hemoglobin <11 g/dl) receiving combination chemotherapy for primary malignant bone tumors were studied in a prospective, double-blind, randomized, Phase III trial. Patients received chemotherapy according to one of two German protocols, depending on histologic diagnosis. All subjects enrolled were randomly assigned either to receive 600 IU of rHuEPO per kg of body weight intravenously twice a week or to receive a placebo during chemotherapy. To obtain comparable data, an observation period of 20 weeks was chosen. Twenty-nine patients fulfilled the criteria and were eligible for statistical evaluation.. Transfusion requirements were significantly decreased from Week 8 of therapy (p<0.05) in the treatment group. Therapeutic benefits were even more evident with continuation of therapy (Week 12, p = 0.03; Week 16, p = 0.016; Week 20, p = 0.002). The blood required was 2.1 units of red cells in the treatment group and 8.4 units of red cells in the placebo group. All patients tolerated rHuEPO with no serious side effects.. These findings suggest that rHuEPO is an effective and well-tolerated therapeutic option for decreasing the transfusion requirements in chemotherapy-induced anemia.

Topics: Adolescent; Adult; Aged; Anemia; Antineoplastic Agents; Blood Cell Count; Bone Neoplasms; Double-Blind Method; Erythropoietin; Female; Humans; Male; Middle Aged; Recombinant Proteins

The discovery of expression of the erythropoietin receptor (EPO-R) on neoplastic cells has led to concerns about the safety of treating anaemic cancer patients with EPO. In addition to its endocrine function, the receptor may play a role in tumour progression through an autocrine mechanism. In this study, the expression of EPO, EPO-R and platelet-derived growth factor BB (PDGF-BB) was analysed in five feline and 13 canine osteosarcomas using immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR). EPO expression was positive in all tumours by IHC, but EPO mRNA was only detected in 38% of the canine and 40% of the feline samples. EPO-R was expressed in all samples by quantitative RT-PCR (RT-qPCR) and IHC. EPO-R mRNA was expressed at higher levels in all feline tumours, tumour cell lines, and kidney when compared to canine tissues. PDGF-BB expression was variable by IHC, but mRNA was detected in all samples. To assess the functionality of the EPO-R on tumour cells, the proliferation of canine and feline osteosarcoma cell lines was evaluated after EPO administration using an alamarBlue assay and Ki67 immunostaining. All primary cell lines responded to EPO treatment in at least one of the performed assays, but the effect on proliferation was very low indicating only a weak responsiveness of EPO-R. In conclusion, since EPO and its receptor are expressed by canine and feline osteosarcomas, an autocrine or paracrine tumour progression mechanism cannot be excluded, although in vitro data suggest a minimal role of EPO-R in osteosarcoma cell proliferation.

Topics: Animals; Becaplermin; Bone Neoplasms; Cat Diseases; Cats; Cell Line, Tumor; Dog Diseases; Dogs; Erythropoietin; Immunohistochemistry; Osteosarcoma; Proto-Oncogene Proteins c-sis; Receptors, Erythropoietin; RNA

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

Tumor anemia is very common in patients with cancer. The causes are very diverse and the parameter value depends on several factors. If this however develops to be symptomatic it may adversely impact health related quality of life. Erythropoietin or blood transfusion provides options for treatment. However, these are not always uneventful. There could also be a lack of response to Erythropoietin. This case report describes the complexity of tumor anemia. It also includes a more detailed discussion on the Fatigue Syndrome, which is one of the most common symptoms of patients with cancer. In the context of palliative care there is often the question of alternatives for improving the quality of patients life. Some kinds of treatment may also cause the opposite effect. A multidimensional assessment should help to approach this difficult issue and to find ways for a meaningful treatment of the symptoms of anemia.

Topics: Adenocarcinoma; Aged; Anemia; Bone Neoplasms; Breast Neoplasms; Combined Modality Therapy; Darbepoetin alfa; Disease Progression; Erythrocyte Transfusion; Erythropoietin; Fatigue; Female; Hematinics; Humans; Medical Futility; Neoplasm Staging; Palliative Care; Quality of Life; Treatment Failure; Treatment Outcome

A 79-year-old man was admitted to the hospital because of a 20-lb weight loss, low back pain, and leg weakness. He had a 1-year history of fibrotic myelodysplasia, possibly therapy related, with a highly complex chromosome karyotype. Radiologic evaluation showed extensive destructive bone lesions, retroperitoneal lymphadenopathy, and evidence for thoracic spinal cord compression. Core biopsies of a retroperitoneal lymph node showed groups of large, immature-appearing mononuclear cells which, on Wright-stained touch preparation, appeared similar to dysplastic erythroid precursors noted on recent marrow aspirate smears. Immunohistochemical staining showed negativity of neoplastic cells to an extensive panel of nonhematopoietic and myeloid markers, and positivity for CD117, glycophorin A, and CD71, consistent with a diagnosis of erythroblastic sarcoma. This lesion is a very unusual variant of myeloid sarcoma and has been described only rarely in the medical literature.

Topics: Abnormal Karyotype; Adenocarcinoma; Aged; Azacitidine; Biopsy, Large-Core Needle; Bone Marrow; Bone Marrow Neoplasms; Bone Neoplasms; Combined Modality Therapy; Disease Progression; Drug Therapy, Combination; Erythroblasts; Erythropoietin; Fatal Outcome; Humans; Lymph Nodes; Male; Myelodysplastic Syndromes; Rare Diseases; Rectal Neoplasms; Sarcoma, Myeloid

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

Use of erythropoietin (EPO) for chemotherapy-induced anemia and biphosphonates (BP) for bone metastasis has increased steadily. However, there are no guidelines on their use in many situations such as non small cell lung carcinoma (NSCLC), which frequently alters quality of life markedly. Therefore, a multicentric survey was designed to assess the treatment of anemia and bone metastasis in chemotherapy-treated patients with non-small-cell lung carcinoma. Nine representative centers of the oncology working party of the French respiratory society (Groupe d'Oncologie de la Société de Pneumologie de Langue Française) participated. Inclusion criteria were stage IV NSCLC and at least one course of chemotherapy in the last 3 months. A total of 148 and 50 patients (pts) were included in the anemia and bone metastasis surveys, respectively. Anemia was present in 60.8% of patients, and was not treated in 75%; 15 patients received EPO (10.1%). Independent predictors of EPO use were presence of anemia-related symptoms, hemoglobin level, age and center: the rate of prescription in patients with anemia varied from 13 to 73% between centers. BP were administered in 38% of patients with bone metastasis. Independent predictors of BP use were calcium serum level, pain, and center with a rate of prescription ranging from 0 to 80% between centers. This study reveals that, in France, most patients with anemia are not treated, EPO being seldom prescribed. The use of both EPO and BP is highly variable between centers. Guidelines on the use of these supportive treatments could help improve the care for lung cancer patients receiving chemotherapy.

Topics: Anemia; Bone Neoplasms; Carcinoma, Non-Small-Cell Lung; Diphosphonates; Erythropoietin; France; Health Surveys; Humans; Lung Neoplasms; Practice Guidelines as Topic; Practice Patterns, Physicians'; Quality of Life

Consorcial projects focused on 5 cancer types, breast-, colorectal-, head and neck- and pediatric cancers, and malignant melanoma. Breast cancer studies revealed unique splicing mechanisms concerning BRCA1. In sporadic breast cancers the involvement of DNA-repair genes was proved to be dependent on the histological type. Bone-metastatic tumors have been characterized by decreased NM23 and increased c-met and p53 expressions. C-erbB2 genotype of the primary tumor was not maintained frequently in bone metastases. Application of DNA-microarray and quantitative PCR technologies improved the prediction of therapeutic sensitivity of breast cancers. Colorectal cancer studies revealed regional inhomogenities (clusters) in various geographical regions of Hungary, which were distinct in the case of colonic and rectal cancers. To increase the sensitivity of fecal blood test of colorectal cancer screening, a new double-antibody test was developed and tested in a large cohort of patients. Genetic analysis revealed that hypermethylation is a significant factor in microsatellite instability which, and plays a role in silencing of APC and E-cadherin genes as well. The Hungarian pattern of TS polymorphism was also determined and was correlated not only with the efficacy of 5-FU treatment but with the progression of the disease as well. Population-based studies have been carried out in head and neck cancer patients (HNC) and smokers as well to reveal the genetic background of increasing tumor incidence. These studies revealed polymorphism in XRCC1/3 methylation enzyme gene which has preventive role. Other studies found frequent local immunosuppression in HNC patients. Studies indicated that the success of irradiation in this cancer type is dependent on the anti-vascular effects. Pediatric cancer studies determined the parameters of neuroblastoma screening based on VMA measurements. New splice variants of the WT1 gene involved in the monitoring of MRD of ALL patients was also described this year. We also obtained positive experimental data for the retinoic acid therapy of ALL. Melanoma studies extensively used DNA-microarray technology which identified 4 melanoma-specific and 2 melanoma progression-specific genes. In experimental human melanoma xenograft models we have identified 3 anti-metastatic agents: low molecular weight heparin, 2-methoxyestradiol and erythropoietin-alpha, where the later was characterized by specific effects on tumor vasculature.

Topics: 2-Methoxyestradiol; Adult; Animals; Antineoplastic Agents; Biomarkers, Tumor; Biomedical Research; Bone Neoplasms; Breast Neoplasms; Child; Colorectal Neoplasms; Disease Models, Animal; Disease Progression; DNA Methylation; Epoetin Alfa; Erythropoietin; Estradiol; Female; Gene Expression Regulation, Neoplastic; Gene Silencing; Genetic Markers; Head and Neck Neoplasms; Heparin, Low-Molecular-Weight; Humans; Hungary; Incidence; Male; Melanoma; Microsatellite Repeats; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Polymorphism, Genetic; Predictive Value of Tests; Recombinant Proteins; Transplantation, Heterologous

The decision about EPO was referred to and made by the Drug Committee, a committee of physicians, nurses and pharmacists. This committee has perforce to make decisions about drugs and vaccines, decisions which sometimes have a significant ethical component due to concerns about cost, safety and efficacy. Our hospital is considering developing a Clinical Ethics Advisory Committee, to assist with difficult ethical decisions such as this one. Should such a committee be asked to make acute ethical judgements on patient management? Larcher describes his ideal Hospital Ethics Committee as nonprescriptive, and suggests a more appropriate role is retrospective analysis and reflective discussion of clinical ethical problems. Such discussion may help with future rather than current management issues, and can help support clinicians in their decisions and hospital staff in their management of patients.

Topics: Anemia; Australia; Bone Neoplasms; Child; Christianity; Erythropoietin; Ethics Committees, Clinical; Ethics, Clinical; Ethics, Medical; Female; Humans; Orthopedic Procedures; Osteochondroma; Parents; Recombinant Proteins; Religion and Medicine; Ribs; Societies, Hospital

Because anemia is associated with reduced long-term survival, and because allogeneic transfusion is linked to increased recurrence of disease and reduced rates of long-term survival, alternative options for managing anemia in the orthopedic oncologic patient have been sought. Managing the anemia of cancer is particularly challenging given the many obstacles to employing conventional blood management options. One potential means of treating perioperative anemia in orthopedic oncologic patients involves the use of Epoetin alfa. The clinical utility of Epoetin alfa in this setting, however, must be determined in controlled trials.

Topics: Anemia; Blood Loss, Surgical; Blood Transfusion, Autologous; Bone Neoplasms; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Recombinant Proteins; Recurrence; Transfusion Reaction

Topics: Bone Neoplasms; Breast Neoplasms; Combined Modality Therapy; Diphosphonates; Erythropoietin; Female; Humans; Male; Neoplasm Metastasis; Neoplasms; Pilot Projects; Radiotherapy

A 24-year-old man with an osteolytic lesion of the ischium was referred to the authors' institution. Computed tomography and magnetic resonance imaging studies showed that the lesion extended to and involved the subchondral bone of the acetabulum. Histologic examination of the biopsy specimen revealed giant cell tumor of bone. Following the biopsy, autologous blood was collected 4 times with recombinant human erythropoietin treatment definitive surgery was performed. Three weeks after the biopsy, the lesion was curetted and bone cementation was performed. The total blood loss during surgery was 3100 ml, which was replaced successfully with stored autologous blood without the need for homologous blood transfusion. The authors believe that without the erythropoietin treatment, autologous blood could have been collected only 3 times instead of 4 times, and the patient would have needed homologous blood.

Topics: Adult; Blood Loss, Surgical; Blood Transfusion, Autologous; Bone Neoplasms; Erythropoietin; Giant Cell Tumor of Bone; Humans; Ischium; Male; Preoperative Care; Recombinant Proteins

Topics: Adolescent; Anemia; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Christianity; Erythropoietin; Humans; Male; Osteosarcoma; Pelvic Bones; Recombinant Proteins

Tumor-induced changes in the pattern of erythropoiesis have been studied in A/RB mice bearing a transplantable ascites tumor, DBA lymphoma. The tumor growth was accompanied by diminished erythropoiesis, and the 51Cr-labeled red cell half-life was also decreased. Plasma iron turnover rate of the tumor bearing hosts, however, was increased and the level of erythropoietic stimulating factor (erythropoietin) in the plasma was not reduced. The existence of an inhibitor(s) to erythropoietic activity was unlikely. Comparative study of the erythropoietic activity revealed suppression in the marrow, but an increment in the spleen. The distribution of pluripotent hematopoietic stem cells (CFUs) also paralleled this alteration. However, the degree of ineffective erythropoiesis, determined by in vitro technique, was significantly elevated in the spleen. Possibly, this has reduced the effectiveness of splenic compensatory erythropoiesis.

Topics: Animals; Bone Neoplasms; Erythrocyte Aging; Erythrocyte Count; Erythrocytes; Erythropoiesis; Erythropoietin; Hemoglobins; Iron; Lymphoma; Male; Mice; Neoplasm Transplantation; Spleen

Topics: Agranulocytosis; Anemia, Aplastic; Anemia, Macrocytic; Bone Marrow Examination; Bone Neoplasms; Breast Neoplasms; Dihydrotestosterone; Erythropoiesis; Erythropoietin; Female; Hepatitis; Humans; Iron; Iron Radioisotopes; Male; Oxymetholone; Prednisolone; Sepsis; Transfusion Reaction