losartan-potassium and Genital-Neoplasms--Female

Neutropenia and anemia are important complications of cancer chemotherapy and can be prevented and treated with granulocyte colony-stimulating factor and erythropoietin.

Topics: Anemia; Antineoplastic Agents; Erythropoietin; Female; Filgrastim; Genital Neoplasms, Female; Granulocyte Colony-Stimulating Factor; Humans; Neutropenia; Quality of Life; Recombinant Proteins

Anemia is a frequent complication of cancer and its treatment. It often impairs the functional status of patients and results in decreased functional capacity and quality of life. Its etiologies are multiple, including chronic inflammation, hemorrhage, nutritional deficiencies, hemolysis, bone marrow suppression by chemotherapy, or infiltration by tumor. It can manifest as feelings of weariness, tiredness, muscular weakness, dysphoric mood, somnolence, or impaired cognitive functioning. In gynecologic patients, the incidence of anemia has been reported to be as high as 80% depending on chemotherapy regimen. Given the various consequences of a low hemoglobin level, the importance of increasing or maintaining hemoglobin levels and ameliorating the symptoms is apparent. Clinical studies have demonstrated that the administration of recombinant human erythropoietin (rHuEPO, epoetin alfa) is effective and safe in increasing hemoglobin levels and improving the overall quality of life in patients with gynecologic cancers undergoing chemotherapy. Therefore, epoetin alfa treatment should be considered in this patient population.

Topics: Anemia; Antineoplastic Agents; Epoetin Alfa; Erythropoietin; Female; Genital Neoplasms, Female; Hematinics; Hemoglobins; Humans; Quality of Life; Recombinant Proteins

A Consensus Conference on the use of recombinant human erythropoietin (rHuEPO, epoetin alfa) in gynecologic tumors was held in Rome in March 1999, and an associated consensus paper has been published in Italian. The current paper updates several discussions that took place at the 1999 meeting concerning epoetin alfa treatment in breast, ovarian, and cervical cancers; the role of epoetin alfa in mobilizing progenitor hematopoietic cells; administration of epoetin alfa in combination with granulocyte colony-stimulating factor; and the effect of hemoglobin levels on outcome of radiation or chemoradiation treatment.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Female; Genital Neoplasms, Female; Granulocyte Colony-Stimulating Factor; Hematinics; Hematopoietic Stem Cell Mobilization; Hemoglobins; Humans; Ovarian Neoplasms; Quality of Life; Radiotherapy, Adjuvant; Recombinant Proteins; Uterine Cervical Neoplasms

The clinical management of gynaecological cancer patients has been mainly focused on prolonging the survival of the patients. Thus, research on MEDLINE using as keywords 'Quality of Life' (QoL) allowed us to identify few papers which reported data on QoL in gynecological oncology. However, the assessment of QoL is becoming one of the most important issues in gynecological oncology, and there is a growing interest in including quality of life measurements in clinical trials. In fact, in several randomised trials on ovarian cancer now ongoing in Europe, the evaluation of QoL has been planned. The one underlying this article focuses on the symptoms and problems particular to gynecologic cancer and the treatments of them that could affect quality of life evaluations. These include limitations of sexual activity and fertility, early menopause, chemotherapy induced toxicity, and loss of body image. In this report, we will discuss the aspects affecting the QoL in gynaecological cancer in relation to surgical treatment, medical therapy, and follow-up.

Topics: Anemia; Clinical Trials as Topic; Erythropoietin; Female; Follow-Up Studies; Genetic Counseling; Genital Neoplasms, Female; Humans; Outcome Assessment, Health Care; Postoperative Complications; Quality of Life; Sexual Dysfunctions, Psychological

Increasing numbers of endocrine active tumors are being reported. The production of hormonal substances not generally associated with the tissues involved may directly or indirectly concern the gynecologist. Identification of these occurrences may be important in the diagnosis of occult neoplasms or obscure tumor effects. In addition, observation of the level of aberrant hormone secretion may be important therapeutic and prognostic measure. Detection may result from the investigation of apparent inappropriate and endocrine syndromes or routine screening in cases of known tumors. Proof of the actual production of hormone by the tumors and complete identification of the material in question generally requires extensive biologic, chemical, physical, and immunologic investigation. The most likely mechanisms for aberrant hormone production by tumors are derepression of the genome or the occurrence of chance biosynthetic anomalies coincident with neoplastic nuclear alterations. Endocrine active substances of interest to the gynecologist produced under these circumstances include gonadotropin, lactogens, thyrotropins, and adrenocortico-tropin, as well as calcium-mobilizing and erythropoietic substances.

Topics: Adrenocorticotropic Hormone; Biological Assay; Chorionic Gonadotropin; DNA; Erythropoietin; Female; Follicle Stimulating Hormone; Genetic Code; Genital Neoplasms, Female; Hormones, Ectopic; Humans; Luteinizing Hormone; Melanocyte-Stimulating Hormones; Neoplasms; Paraneoplastic Endocrine Syndromes; Parathyroid Hormone; Peptides; Placental Lactogen; Pregnancy; Prolactin; Radioimmunoassay; RNA, Messenger; Serotonin; Thyrotropin; Transcription, Genetic

Erythropoietin-stimulating agents (ESAs) effectively decrease the transfusion requirements of patients with chemotherapy-induced anaemia (CIA). Recent studies indicate that ESAs increase mortality and accelerate tumour progression. The studies also identify a 1.6-fold increased risk of venous thromboembolism. The ESA labelling was thus revised in Europe and the United States in 2008. This is the first randomised, phase III trial evaluating the efficacy and safety of epoetin-β (EPO), an ESA, dosed in accordance with the revised labelling, which specifies that ESAs should be administered to CIA patients with a haemoglobin level of ≤ 10 g dl⁻¹ and that a sustained haemoglobin level of > 12 g dl⁻¹ should be avoided.. A total of 186 CIA patients (8.0 g dl⁻¹ ≤ haemoglobin ≤ 10.0 g dl⁻¹) with lung or gynaecological cancer were randomised to receive EPO 36,000 IU or placebo weekly for 12 weeks.. The proportion of patients receiving transfusions or with haemoglobin < 8.0 g dl⁻¹ between week 5 and the end of the treatment period as the primary end point was significantly lower in the EPO group (n=89) than in the placebo group (n=92; 10.0% vs 56.4%, P < 0.001). The proportion receiving transfusions was significantly lower in the EPO group (4.5% vs 19.6%, P=0.002). Changes in quality of life were not different. No significant differences in adverse events - for example, the incidence of thromboembolic events was 1.1% for each group - or the 1-year overall survival were observed between groups.. Weekly EPO administered according to the revised labelling approved by the European Medicines Agency is effective and well tolerated for CIA treatment. Further investigations are needed on the effect of ESAs on mortality.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Erythropoietin; Female; Genital Neoplasms, Female; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Placebos; Quality of Life; Recombinant Proteins

The purpose of this prospective study was to investigate the efficacy of preoperative administration of recombinant human erythropoietin in patients with gynecological cancer.. The study included 38 women with gynecological cancer who were divided randomly in two groups. Study group A included 20 women with gynecological cancer who received recombinant human erythropoietin (rHuEPO) plus iron supplementation for ten days before surgery and five days postoperatively. Group B (controls) included 18 patients who received only iron supplementation for the same time period. Blood samples were obtained on days -10, -3, 0, +3, +5, +10.. The mean hemoglobin level was significantly higher in group A than in group B on the day of the operation and remained significantly higher postoperatively while an inverse relationship was observed for mean ferritin values in the two groups.. Preoperative administration of rHuEPO in patients with gynecological cancer seems to be effective in the blood management of these patients.

Topics: Adult; Aged; Confidence Intervals; Dose-Response Relationship, Drug; Drug Administration Schedule; Erythropoietin; Female; Follow-Up Studies; Genital Neoplasms, Female; Gynecologic Surgical Procedures; Humans; Iron Compounds; Middle Aged; Neoplasm Staging; Preoperative Care; Probability; Prospective Studies; Recombinant Proteins; Reference Values; Risk Assessment; Survival Analysis; Treatment Outcome

An important clinical question is the relative efficacy of the most common dosages of darbepoetin alfa (Aranesp; Amgen Inc.; Thousand Oaks, CA) 200 microg every 2 weeks (Q2W) and epoetin alfa (Procrit; Ortho Biotech Products, LP; Raritan, NJ) 40,000 U weekly (QW) for the treatment of chemotherapy-induced anemia. We designed three concurrent randomized, open-label, multicenter, identical trials (with the exception of tumor type criteria of breast, gynecologic, or lung cancer) of darbepoetin alfa and epoetin alfa in patients with chemotherapy-induced anemia to validate the Patient Satisfaction Questionnaire for Anemia (PSQ-An) treatment tool and to compare the efficacies and safety profiles of these two agents. In each trial, patients were randomized 1:1 to receive either darbepoetin alfa at a dose of 200 microg Q2W or epoetin alfa at a dose of 40,000 U QW for up to 16 weeks. The PSQ-An was assessed for validity, feasibility, and reliability. Secondary clinical endpoints were analyzed using the primary analysis set. Both individual trial analyses and a protocol-specified combined analysis of data from all three trials were conducted. Overall, 312 patients (157 darbepoetin alfa; 155 epoetin alfa) were randomized and received study drug. Baseline characteristics were similar in both treatment groups in each trial and overall. The PSQ-An was valid, feasible, and reliable. In general, no difference between treatment groups was observed for hemoglobin- and transfusion-based endpoints in each individual trial or in the combined analysis. From exploratory analyses, achievement and maintenance of a hemoglobin target range (11-13 g/dl) were similar in both groups. No differences in safety were observed. With the PSQ-An, formal comparisons of the impact of anemia therapies on patients and caregivers can be made in future prospective studies. Further, darbepoetin alfa (200 microg Q2W) and epoetin alfa (40,000 U QW) appear to achieve comparable clinical and hematologic outcomes.

Topics: Anemia; Antineoplastic Agents; Breast Neoplasms; Darbepoetin alfa; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Genital Neoplasms, Female; Hematinics; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Prospective Studies; Quality of Life; Recombinant Proteins; Reproducibility of Results; Surveys and Questionnaires

The objectives of this study were to assess the safety and efficacy of darbepoetin alfa (Aranesp) administered every 2 weeks in anemic patients with solid tumors receiving chemotherapy. This was an open-label, randomized, active-controlled, multicenter dose-finding study evaluating a range of every-2-week darbepoetin alfa doses. The active control arm received epoetin alfa (Epogen, Procrit) at 40,000 U weekly with a dose increase to 60,000 U weekly for subjects with an inadequate response. The lowest clinically effective doses of darbepoetin alfa in this study were 3.0 and 5.0 microg/kg every 2 weeks, with no additional benefit observed at higher doses. The percentage of patients who achieved a hematopoietic response in the 3.0- and 5.0-microg/kg groups was 66% (95% confidence interval [CI] = 46%-86%) and 84% (95% CI = 67%-100%), respectively, compared with 63% (95% CI = 46%-81%) in the epoetin alfa group. Darbepoetin alfa administered at a dose of 3.0 microg/kg every 2 weeks is safe and effective for treating anemia in patients with solid tumors on chemotherapy, and is comparable to epoetin alfa. A dose increase to 5.0 microg/kg of darbepoetin alfa administered every 2 weeks may be appropriate in patients with an inadequate initial response.

Topics: Anemia; Breast Neoplasms; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Gastrointestinal Neoplasms; Genital Neoplasms, Female; Genital Neoplasms, Male; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasms; Recombinant Proteins; Treatment Outcome

Twenty-seven anemic patients with malignant tumour who received chemotherapy were treated with recombinant human erythropoietin (r-HuEPO). The objective of this study was to evaluate the effect of r-huEPO on hematologic and quality of life parameters as well as on transfusion requirement in patients with anemia secondary to cancer and cyclic chemotherapy. Patient population was allocated into two groups based on the chemotherapeutic regimens: 1. cisplatin containing and 2, non cisplatin containing regimen. Using 2 g/dl increase in haemoglobin levels as the criteria for response, twenty women responded to r-huEPO treatment. The response was more marked in the cisplatin group. R-huEPO treatment saved transfusion in both groups. Again, less patients required transfusion among those treated with cisplatin. There was a marked improvement in the quality of life which was more pronounced in patients who responded to r-huEPO treatment and in those receiving non cisplatin chemotherapy. No serious adverse experiences occurred. In conclusion, two third of patients with anemia secondary to cancer and cyclic chemotherapy can be effectively treated with r-huEPO. R-huEPO treatment invariably saves transfusion and is highly effective in improving quality of life. Adverse reaction is exceptional.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Cisplatin; Erythropoietin; Female; Genital Neoplasms, Female; Humans; Informed Consent; Treatment Outcome

Anemia is frequent in cancer patients, is the result of decreased erythropoietin production. In fact in cancer, alteration of immune system alters iron metabolism and inhibits erythropoietin production. In this study we proposed to determine the profile of erythropoietin secretion in anaemic cancer patients in the pre and postoperative period. Our prospective study from January to March 2005 included 41 anemic cancer patients from 30 to 79 years old and 31 healthy individuals with iron deficiency anemia. A measure of erythropoietin, CRP, ferritin, iron levels and hemoglobin were released in healthy individuals and in cancer patients in preoperative period (J0) and postoperative period (J3, J8, J21). In preoperative period, the increase of serum erythropoietin was significantly lower in patients than in healthy individuals. In postoperative period, the levels of erythropoietin at J3 and hemoglobin's at J8 and J21 were significantly higher than in preoperative period (J0) (p < 0.05). In conclusion, despite the presence of inflammatory syndrome caused by surgery, cancer patients with anaemia increase their erythropoietin production in immediate postoperative period.

Topics: Adult; Aged; Anemia; Anemia, Iron-Deficiency; C-Reactive Protein; Digestive System Neoplasms; Erythropoietin; Female; Ferritins; Genital Neoplasms, Female; Hemoglobin A; Humans; Male; Middle Aged; Postoperative Period; Prospective Studies; Time Factors

Chemotherapy induced anemia (CIA) commonly occurs in gynecologic oncology patients. This often leads to treatment with erythropoietic stimulating agents in order to prevent chemotherapy delays, dose modifications and transfusion of red blood cells. Our objective was to determine the subsequent transfusion rates following administration of either darbepoetin alfa or epoetin alfa.. A single institution retrospective chart review was performed utilizing patients from January 2003 to September 2004 who received either darbepoetin alfa or epoetin alfa for CIA (Hgb < or = 10.0). Data collection variables included patient demographics, cancer diagnosis, chemotherapy treatment(s), laboratory data, erythropoeisis stimulation data, and transfusions. Sample size calculations were set to detect a 20% transfusion rate difference between the two groups. Chi-square, Fisher exact test and student t tests were used for statistical analysis.. 123 patients were eligible for analysis (60 darbepoetin alfa; 62 epoetin alfa). 93% of darbepoetin alfa patients received 200 mg every other week, while 86% of epoetin alfa patients received 40,000 U weekly. The darbepoetin alfa and epoetin alfa groups were similar in respect to age, race, tumor type, histology, previous chemotherapy, number of chemotherapy agents, weeks of erythropoietic stimulation, and baseline serum levels of creatinine and hemoglobin. The mean baseline Hgb and change in Hgb was similar for each group (darbepoetin alfa = 11.2, 2.5 and epoetin alfa = 11.3, 2.3). Twenty one (35%) of the darbepoetin alfa patients received a transfusion of packed red blood cells compared to 12 (19%) of epoetin alfa patients (p = 0.05).. This retrospective analysis powered to detect differences in transfusion rates revealed a statistically significant difference in transfusion rates between darbepoetin alfa and epoetin alfa for the treatment of CIA. These data warrant a randomized prospective trial in gynecologic oncology patients with careful attention to the timing of initiation of treatment, dosing regimens, and titration of growth factor.

Topics: Anemia; Antineoplastic Agents; Blood Transfusion; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Female; Genital Neoplasms, Female; Hematinics; Hemoglobins; Humans; Middle Aged; Recombinant Proteins; Retrospective Studies

We had previously reported an association between the use of recombinant human erythropoietin (rHuEPO) and thrombosis in patients with cervix and vulvo-vaginal cancer treated with chemotherapy and radiation. We hypothesized that low-dose warfarin would be effective prevention for thromboembolic events in this setting.. A retrospective analysis of patients with cervical or vulvo-vaginal carcinoma receiving chemoradiation and rHuEpo was performed. Thirty-two patients received rHuEpo alone, and 24 received warfarin (1-2 mg) and rHuEpo. The primary endpoint was objectively proven symptomatic venous thrombosis.. There was no difference in the baseline characteristics (e.g. age, stage, body mass index, mean and peak hemoglobin, WBC and platelet counts, and number of transfusions) between these two groups. The rate of thrombosis also was not statistically different (P = 0.62). Nine of 24 patients had a symptomatic deep vein thrombosis (DVT) while receiving warfarin compared to 10 of 32 patients not on warfarin. There was no difference between the two groups in the percentage of patients with upper extremity DVT (P = 0.83) or lower extremity DVT (P = 0.64).. Daily low-dose warfarin did not alter the incidence of symptomatic DVT in patients with cervical or vulvo-vaginal cancer who received rHuEpo in conjunction with chemoradiation.

Topics: Anticoagulants; Dose-Response Relationship, Drug; Erythropoietin; Female; Genital Neoplasms, Female; Humans; Middle Aged; Recombinant Proteins; Retrospective Studies; Thrombosis; Uterine Cervical Neoplasms; Vaginal Neoplasms; Vulvar Neoplasms; Warfarin

Treating anemia associated with chemotherapy and many cancers is often necessary. However, patient satisfaction with anemia treatment is limited by the lack of validated instruments. We developed and validated a new treatment-specific patient satisfaction instrument: the Patient Satisfaction Questionnaire for Anemia Treatment (PSQ-An). Treatment burden and overall satisfaction scales were designed for ease of use in clinical practice.. 312 cancer patients (141 breast, 69 gynecological, and 102 non-small cell lung) were targeted to complete the PSQ-An at 4 week intervals. Data from weeks 5 and 9 were analyzed. Patients also completed the MOS SF-36 Global Health assessment and questions concerning resources devoted to anemia treatment. Item reduction used endorsement rates, floor/ceiling effects, and item-item correlations. Factor analysis identified meaningful subscales. Test-retest reliability was assessed. Construct validity was tested, using Pearson's correlations, by comparing subscale scores to Global Health, hemoglobin levels, and resources devoted to anemia treatment.. The overall response rate was 92.9% (264/284) at week 5. Most (84.2%) of the patients were female, and the mean (SD) age was 60.2 (+/- 11.8) years. Two distinct subscales were identified measuring treatment burden (7 items) and overall satisfaction (2 items). Test-retest reliability was examined (ICC: 0.45-0.67); both were internally consistent (alpha = 0.83). Both subscales exhibited convergent and divergent validity with independent measures of health. ANOVA results indicated that the PSQ-An Satisfaction subscale discriminated between 5 levels of MOS SF-36 Global Health (P = 0.006).. The PSQ-An is a validated, treatment-specific instrument for measuring satisfaction with anemia treatment for cancer patients. PSQ-An subscales reflect the burden of injection anemia treatment on cancer patients and their assessment of the overall treatment value.

Topics: Aged; Anemia, Hemolytic; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Darbepoetin alfa; Epoetin Alfa; Erythropoietin; Factor Analysis, Statistical; Female; Genital Neoplasms, Female; Hematinics; Humans; Karnofsky Performance Status; Male; Middle Aged; Multicenter Studies as Topic; Outcome Assessment, Health Care; Patient Satisfaction; Psychometrics; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Surveys and Questionnaires

The objective of this study was to establish a novel method of preoperative autologous blood donation (PAD) for surgery of gynecologic malignancies, which requires considerable amounts of plasma relative to the red blood cell component. To collect a double volume of plasma over the amount obtained from whole blood without using an aphaeresis system, we first collected 500 ml of whole blood (2.5 units), and centrifuged it. We gave back the resultant red cell component alone, and retained the plasma component. We further collected an additional 500 ml of whole blood, and centrifuged it. The red cell component (2.5 units) was stored in the refrigerator (as a concentrated red cell, CRC). The resultant plasma together with the plasma collected first (5 units) was frozen and stored in the freezer (fresh frozen plasma, FFP), We repeated this procedure at most three times at intervals of 1 week. Erythropoietin was injected once a week and iron tablets were prescribed. Ninety-nine patients undergoing surgery for a gynecological malignancy were subjected to this method and 86 patients without PAD served as a control. We conducted the procedure for PAD without any noticeable side effects. The amount of actual use of allogeneic CRC and FFP were significantly reduced in the PAD group compared with the control group. In particular, 93.6% of the PAD cases who gave 10 or less units of FFP could go without allogeneic FFP. Postoperative serum albumin levels were higher in the PAD group compared with the control. We have established a novel PAD method which can yield a greater volume of FFP relative to CRC, thus meeting requirements for surgery for gynecological malignancies.

Topics: Blood Loss, Surgical; Blood Specimen Collection; Blood Transfusion, Autologous; Epoetin Alfa; Erythropoietin; Female; Genital Neoplasms, Female; Hematinics; Hemoglobins; Humans; Patient Selection; Plasma Volume; Preoperative Care; Recombinant Proteins

Topics: Antigens, CD34; Cytokines; Erythropoietin; Female; Genital Neoplasms, Female; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Humans; Middle Aged; Stem Cells; Transplantation Conditioning

To investigate the possible benefits of erythroproietin ingestion in patients with various gynecological cancers with proven severe iron deficiency anemia.. Seven patients with gynecological cancer were included in the study. Nadir hematocrit values were found to be 20-24% before the initiation of recombinant human erythropoietin treatment. Initial therapy started at 50 units/kg/dose, three times weekly for a month. The dose was modified according to the rise of hemoglobin after a month's period. The dose was modified according to the rise of hemoglobin after a month's period. If the rise was greater than 2 g/dl the dose was changed to 25 units/kg two times weekly and if it was less than 2 g/dl it was changed to 25 units/kg three times weekly per month. Five patients were simultaneously given erythropoietin therapy and iron supplementation.. We confirmed a rise in the hematocrit values which averaged 0.5-1.5% weekly till the upper limit. Reticulocyte and hematocrit values were higher in the erythropoietin plus iron group (five cases).. In this small series, erythropoietin appeared to be effective in treating severe iron deficiency in gynecologic cancer patients. Further investigation is needed to confirm these results.

Topics: Anemia, Iron-Deficiency; Drug Administration Schedule; Erythropoietin; Female; Genital Neoplasms, Female; Hematocrit; Humans; Injections, Subcutaneous; Recombinant Proteins; Treatment Outcome

The accumulating evidence that erythropoietin and erythropoietin receptor are expressed in various non-haematopoietic organs suggests that erythropoietin signalling might be involved in the growth of tumours, but this possibility has never been examined. We found that mRNAs for erythropoietin and erythropoietin receptor are expressed in malignant tumours of female reproductive organs, where erythropoietin levels are higher than in normal tissues. Furthermore, tumour cells and capillary endothelium showed erythropoietin receptor immunoreactivity. To investigate the role of the erythropoietin/erythropoietin receptor pathway in these tumours, we injected mouse monoclonal antibody against erythropoietin or the soluble form of erythropoietin receptor into blocks of tumour specimens and cultured the blocks. After 12 h of injections, these blocks were examined and compared with control blocks injected with mouse monoclonal antibody, heat denatured soluble form of erythropoietin receptor, mouse serum or saline. Tumour cells and capillaries were markedly decreased in a dose-dependent manner after either injection. A marked increase of the cells containing fragmented DNA and the histopathological characteristics of these cells suggest that the decrease in tumour cells and capillary endothelial cells was due to apoptotic cell death. The co-existence of JAK2 and phosphorylated-JAK2, and STAT5 and phosphorylated STAT5, all of which are involved in the mitogenic signalling of erythropoietin, was found frequently in tumour cells and capillary endothelial cells in the untreated blocks. In contrast, most of the phosphorylated-JAK2- or phosphorylated-STAT5-positive cells had disappeared in the experimental blocks. Moreover, reduced tyrosine phosphorylation of STAT5 in the experimental blocks was confirmed by western blotting analysis. The results strongly indicate that erythropoietin signalling contributes to the growth and/or survival of both transformed cells and capillary endothelial cells in these tumours. Thus, deprivation of erythropoietin signalling may be a useful therapy for erythropoietin-producing malignant tumours.

Topics: Animals; Antibodies, Monoclonal; Capillaries; DNA-Binding Proteins; Endothelium, Vascular; Erythropoietin; Female; Gene Expression Regulation, Neoplastic; Genital Neoplasms, Female; Humans; Janus Kinase 2; Mice; Milk Proteins; Neoplasm Proteins; Neovascularization, Pathologic; Phosphorylation; Protein Processing, Post-Translational; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Receptors, Erythropoietin; RNA, Messenger; RNA, Neoplasm; Signal Transduction; STAT5 Transcription Factor; Trans-Activators

Our objective was to assess, using clinical trial simulation, the feasibility of a fixed 200-microg dose of darbepoetin alfa (Aranesp) administered every 2 weeks in chemotherapy-induced anemia. A pharmacokinetic/pharmacodynamic model was developed using clinical data from 547 cancer patients who received darbepoetin alfa at various doses and schedules. Monte Carlo simulations were performed for weight-based (3 microg/kg every 2 weeks) and fixed-dose (200 microg every 2 weeks) regimens and were compared with observed clinical data. Mean hemoglobin changes from baseline to end of treatment were +1.61 g/dL, +1.83 g/dL, and +1.79 g/dL for observed data, the weight-based simulation, and the fixed-dose simulation, respectively. The rates of required transfusions (hemoglobin < or = 8 g/dL) were also similar between groups. For patients between 45 and 95 kg (over 90% of the population), the impact of a fixed dose on mean hemoglobin change was negligible. There was a slight weight effect at body weight extremes (< 45 kg and > 95 kg). Clinical outcomes from simulations of weight-based andfixed dosing of darbepoetin alfa were similar to those of observed weight-based data. Given the weight distribution of a typical cancer population, the majority would be expected to benefit equally from weight-based and fixed-dose darbepoetin alfa in the amelioration of chemotherapy-induced anemia.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Body Weight; Breast Neoplasms; Clinical Trials as Topic; Computer Simulation; Darbepoetin alfa; Drug Administration Schedule; Erythropoietin; Female; Gastrointestinal Neoplasms; Genital Neoplasms, Female; Genital Neoplasms, Male; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Monte Carlo Method

The use of r-HuEPO and sodium ferrous gluconate has been shown to be a safe and effective treatment which can be used by transfusional centers and surgeons to avoid allogeneic blood transfusions and to schedule short-term selective surgery. In this study the authors submitted 20 patients scheduled to undergo surgery for gynecological tumors to a program of pre-operative autologous blood donation. All the patients received both r-HuEPO and sodium ferrous gluconate in the pre- and post-donation period. r-HuEPO was administered subcutaneously in a dose of 200 IU/kg thrice weekly during the week before and after autologous blood donation (400 ml). Sodium ferrous gluconate was administered intravenously shortly before the first and fourth administration of 125 mg of r-HuEPO. Surgery was scheduled to be performed 10-15 days after the last r-HuEPo administration, i.e. within 15-20 days from blood donation. All the patients were tested for the following blood chemistry parameters: hematocrit, hemoglobin, sideremia and ferritin at treatment start, prior to donation, at treatment end, prior to autologous blood infusion and on the third and seventh day after surgery. No patient receiving r-HuEPO required allogeneic blood transfusion as both the hematocrit and hemoglobin values remained normal. r-HuEPO was observed to be a safe and effective treatment to be used in autologous blood donation programs in all patients scheduled to undergo surgery. It limits the decrease of hematocrit values following autologous blood donation thus enabling all the patients who for a variety of reasons to refuse allogeneic blood infusion to predeposit autologus blood shortly before the date scheduled for surgery.

Topics: Adult; Blood Transfusion, Autologous; Erythropoietin; Female; Genital Neoplasms, Female; Hematocrit; Hemoglobins; Humans; Middle Aged; Recombinant Proteins

To apply recombinant human (rh)erythropoietin (EPO) to predeposit autologous blood donation (P.A.B.D.) in cancer patients clinically, (1) we tested the effects of rh-EPO on 2 ovarian cancer cell lines in vitro at first, then, (2) studied the effect of the rh-EPO for switch back (SB) method that is a variant of P.A.B.D. clinically. Rh-EPO (0.068-68U/ml) caused no significant and reproducible stimulation of clonal growth to SHIN-3 (derived from serous cyst adenocarcinoma) and MN-1 (derived from mucinous cyst adenocarcinoma). Twenty-five cases were studied. The change in the hemoglobin concentration (delta Hb) was -0.43 +/- 1.38g/dl (mean +/- SD) and the change in the total amount of hemoglobin (total delta Hb) which is calculated on the basis of whole blood volume was 111.5 +/- 53.2g/body in 16 cases with rh-EPO. The delta Hb and total delta Hb were -3.25 +/- 0.78g/dl and 30.1 +/- 41.7g/body in 9 cases without rh-EPO. The rh-EPO combined cases were significantly increased in both delta Hb and total delta Hb (p < 0.05, unpaired student t test). We therefore conclude that it would be very beneficial to use rh-EPO combined with the SB method in P.A.B.D. for high maximum surgical blood order schedule (MSBOS) cases such as gynecological malignancies.

Topics: Adult; Aged; Blood Transfusion, Autologous; Cell Division; Cystadenocarcinoma, Mucinous; Cystadenocarcinoma, Serous; Erythropoietin; Female; Genital Neoplasms, Female; Humans; Middle Aged; Ovarian Neoplasms; Recombinant Proteins; Tumor Cells, Cultured

Topics: Anemia; Erythropoietin; Female; Genital Neoplasms, Female; Humans; Middle Aged; Recombinant Proteins

Erythropoietin levels have been determined in 24 patients with different gynecologic malignancies, who were treated with cisplatinum and endoxan. A statistically highly significant decrease was demonstrated 2 h after starting treatment with a further significant decrease at 6 h. After 12 h the erythropoietin concentrations returned to values similar to those before treatment started.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Cyclophosphamide; Erythropoietin; Female; Genital Neoplasms, Female; Humans; Middle Aged

To investigate the participation of erythropoietin (Epo) in anemias induced by cisplatin combined chemotherapy, serum Epo levels were measured by radioimmunoassay on a serial basis in eight patients with gynecologic cancer undergoing this chemotherapy. The data demonstrated that serum Epo levels, the mean level before chemotherapy being 20.1 +/- 6.6 mU/ml, were significantly elevated after the first course of the chemotherapy (52.1 +/- 32.2 mU/ml; P less than 0.05) when anemia was not evident. The serum Epo level continued to increase as the course of chemotherapy advanced, and furthermore, patients with normocytic anemia after a multiple course of this chemotherapy still showed high Epo levels (115.2 +/- 53.5 mU/ml) that were appropriate for given degrees of anemia. It is suggested that cisplatin combined chemotherapy caused the elevated serum Epo levels through an unknown mechanism other than anemia, and that in anemias induced by cisplatin, Epo deficiency is not evident.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Erythropoietin; Female; Genital Neoplasms, Female; Hematocrit; Hemoglobinometry; Humans; Prospective Studies; Radioimmunoassay

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma; Drug Interactions; Erythropoietin; Female; Genital Neoplasms, Female; Growth Substances; Hematopoietic Cell Growth Factors; Humans; Middle Aged