losartan-potassium and Colonic-Neoplasms

Topics: Adenocarcinoma; Adrenocorticotropic Hormone; Arginine; Biliary Tract Diseases; Bronchial Neoplasms; Carcinoma; Chorionic Gonadotropin; Colonic Neoplasms; Cushing Syndrome; Erythropoietin; Female; Follicle Stimulating Hormone; Growth Hormone; Gynecomastia; Hormones, Ectopic; Humans; Hypercalcemia; Lactation Disorders; Lung Neoplasms; Luteinizing Hormone; Models, Biological; Neoplasms; Paraganglioma; Paraneoplastic Endocrine Syndromes; Polycythemia; Pregnancy; Prolactin; Thyroid Neoplasms; Vasopressins

One hundred patients scheduled for elective colo-rectal cancer surgery, and with a preoperative haemoglobin level < or = 8.5 mmol/l were included. Eighty-one patients could be evaluated. Thirty-eight patients received r-HuEPO in a dose of 300 IU/kg body weight on day four before surgery and 150 IU/kg, daily, for the following seven days, and 43 patients received placebo. In addition, all patients received daily doses of 200 mg iron, orally, for four days before surgery. On the day of surgery and until discharge the haemoglobin concentration was significantly higher in the erythropoietin group compared to the placebo group. The number of blood transfusions given was significantly lower in the erythropoietin group with a mean of 0.3 units per patient (0-6) compared to 1.6 units (0-9) in the control group (p < 0.05). The clinical implications of these findings has yet to be assessed.

Topics: Adult; Aged; Blood Loss, Surgical; Blood Transfusion; Colonic Neoplasms; Double-Blind Method; Erythropoietin; Female; Hemoglobins; Humans; Intraoperative Care; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Rectal Neoplasms; Transfusion Reaction

The possible immunosuppressive effect of blood transfusion and its influence on survival after surgery for cancer makes it worthwhile to seek methods to avoid transfusion wherever possible. Patients with right-sided colonic cancer are frequently anaemic. Such patients were entered into a study that employed erythropoietin to avoid homologous transfusion.. In a prospectively randomized double-blind placebo-controlled multicentre trial, patients with moderate anaemia (haemoglobin concentration greater than 8.5 g/dl and less than or equal to 13.5 g/dl) presenting with right-sided colonic cancer and scheduled for hemicolectomy were treated with recombinant human erythropoietin (epoetin beta) 20,000 units/day subcutaneously or placebo for at least 10 days over the operative period.. Perioperative treatment with epoetin beta was well tolerated and there were no significant differences in morbidity and mortality. Following hemicolectomy, median cumulative blood loss in the two groups was similar (epoetin beta 440 ml versus placebo 345 ml). Sixteen (33 per cent) of 48 patients treated with epoetin beta and 15 (28 per cent) of 54 in the placebo group received perioperative blood transfusions (P not significant). The increase in reticulocyte count between baseline and the last preoperative value was more pronounced in the epoetin beta group than in those receiving placebo (P = 0.036).. Despite the perioperative administration of 20,000 units erythropoietin per day for at least 10 days, it was not possible to reduce the intraoperative and postoperative transfusion need. None the less, a positive change in the haematological variables of treated patients was clearly discernible. The negative result may be due to the short treatment interval and to iron deficiency, which was present in the majority of patients. The general change of attitude towards allogeneic blood transfusion is demonstrated by the overall low frequency of blood transfusion in this study.

Topics: Aged; Anemia; Blood Transfusion; Colectomy; Colonic Neoplasms; Double-Blind Method; Erythropoiesis; Erythropoietin; Female; Humans; Intraoperative Care; Male; Middle Aged; Postoperative Care; Postoperative Hemorrhage; Prospective Studies; Recombinant Proteins; Reticulocyte Count

The aim of this study was to determine whether the preoperative administration of recombinant human erythropoietin (rHuEPO) could increase the rate of autologous blood donation and reduce the perioperative need for homologous blood in anaemic patients with cancer. Twenty-two anaemic (haematocrit less than 34 per cent), iron-deficient (iron less than 700 micrograms/l) patients, with gastric or colorectal cancer scheduled for elective surgery, were allocated randomly to two groups. The first (n = 11) received iron saccharate 200 mg/day intravenously for 12 consecutive days. The second (n = 11) received rHuEPO subcutaneously (300 units/kg as first administration, and 100 units/kg 4, 8 and 12 days later) with supplemental iron. On days 4, 8 and 12, if the haematocrit was greater than 34 per cent, patients donated one unit (350 ml) of autologous blood. In the iron group the mean haematocrit did not change from admission (31 per cent) to day 12 of treatment (31 per cent), and no patient could donate autologous blood. In the rHuEPO group, eight patients donated two units of autologous blood and three donated one unit. Four patients in the iron group received perioperative transfusion of homologous blood compared with none in the rHuEPO group. Administration of rHuEPO facilitated the donation of autologous blood and reduced perioperative homologous blood transfusion in anaemic patients with cancer.

Topics: Adolescent; Adult; Aged; Anemia, Iron-Deficiency; Blood Transfusion, Autologous; Colonic Neoplasms; Erythropoietin; Female; Humans; Male; Middle Aged; Preoperative Care; Prospective Studies; Recombinant Proteins; Rectal Neoplasms; Stomach Neoplasms

Topics: Adenocarcinoma; Amidines; Anemia; Antimalarials; Clinical Trials as Topic; Colonic Neoplasms; Erythropoietin; Humans; Levamisole; Malaria; Mefloquine; Pentamidine; Pneumonia, Pneumocystis; Quinolines; Recombinant Proteins

Bruton's tyrosine kinase (Btk) is a non-receptor tyrosine kinase involved in the activation of signalling pathways responsible for cell maturation and viability. Btk has previously been reported to be overexpressed in colon cancers. This kind of cancer is often accompanied by anaemia, which is treated with an erythropoietin supplement. The goal of the present study was to assess the effects of combination therapy with erythropoietin β (Epo) and LFM-A13 (Btk inhibitor) on colon cancer in in vitro and in vivo models.. DLD-1 and HT-29 human colon adenocarcinoma cells were cultured with Epo and LFM-A13. Cell number and viability, and mRNA and protein levels of Epo receptors, Btk and Akt were assessed. Nude mice were inoculated with adenocarcinoma cells and treated with Epo and LFM-A13.. The combination of Epo and LFM-A13 mostly exerted a synergistic inhibitory effect on colon cancer cell growth. The therapeutic scheme used effectively killed the cancer cells and attenuated the Btk signalling pathways. Epo + LFM-A13 also prevented the normal process of microtubule assembly during mitosis by down-regulating the expression of Polo-like kinase 1. The combination of Epo and LFM-A13 significantly reduced the growth rate of tumour cells, while it showed high safety profile, inducing no nephrotoxicity, hepatotoxicity or changes in the haematological parameters.. Epo significantly enhances the antitumour activity of LFM-A13, indicating that a combination of Epo and LFM-A13 has potential as an effective therapeutic approach for patients with colorectal cancer.

Topics: Agammaglobulinaemia Tyrosine Kinase; Amides; Animals; Antineoplastic Combined Chemotherapy Protocols; Cell Count; Cell Cycle Proteins; Cell Line, Tumor; Cell Survival; Colonic Neoplasms; Colorectal Neoplasms; Drug Synergism; Erythropoietin; Humans; Mice; Nitriles; Polo-Like Kinase 1; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-akt; Receptors, Erythropoietin; Xenograft Model Antitumor Assays

Cancer patients treated with alkylating agents and radiotherapy are exposed to high level of reactive oxygen species (ROS) in tissues. ROS can involve superoxide free radicals, peroxynitrite, singlet oxygen, nitric oxide and hydrogen peroxide. It is well documented that increased exposure to oxygen through a high metabolic rate could lead to a shortened life span. Ionizing radiation, use of drugs and the development of cancer can lead to cancer-induced anemia. Recombinant human erythropoietin (Epo) supplementation is one of the methods for treating anemia. Erythropoietin through an increase in the number of erythrocytes, improves oxygenation tissue. The aim of this work was to study the effect of Epo on colon adenocarcinoma cells (DLD-1) given alone or in combination with hydrogen peroxide (H2O2). Cell proliferation and number were measured.. Expression of EpoR, Bcl-2 and Akt1 protein was assessed by RT-PCR, Western blot, and confocal microscopy.. The results show that the coadministration of Epo and H2O2 indicates antitumor action, which occurs via a dose-dependent inhibition of DLD-1 cell growth and proliferation. Moreover, the coadministration of Epo and H2O2 resulted in a decrease of cell numbers, as well as Bcl-2 expression. The incubation of DLD-1 cells with those agents led to a decrease in EpoR and phosphorylated EpoR expression and an increase in Akt1 and phosphorylated Akt expression. The addition of Epo to H2O2 intensified the cytotoxic effect of the latter.. These preclinical results suggest that Epo during chemotherapy or radiotherapy may possess potential benefits in colon cancer patients.

Topics: Cell Count; Cell Culture Techniques; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colonic Neoplasms; Dose-Response Relationship, Drug; Erythropoietin; Humans; Hydrogen Peroxide; Nitric Oxide; Phosphorylation; Proto-Oncogene Proteins c-akt; Receptors, Erythropoietin; Signal Transduction

Paraneoplastic erythrocytosis can be brought on by ectopic erythropoietin production usually in kidney, brain, and liver tumor with increase of serum erythropoietin level. We report here a paraneoplastic erythrocytosis of colon cancer with serum erythropoietin within the normal reference, which required an immunohistologic test for erythropoietin-antibody to be diagnosed.. Our case report was of a 75-year-old woman with erythrocytosis. Her hemoglobin and serum erythropoietin levels were 191 g/dL and 12.6 IU/L (reference range, 9.1-32.8), respectively. Colonoscopy revealed an advanced sigmoid colon tumor 20 mm in diameter. She underwent colectomy, and immunohistochemical examination showed the colon adenocarcinoma was focally positive for erythropoietin-antibody. One month after the surgery, her hemoglobin level decreased to 117 g/L.. Colon cancer can cause paraneoplastic erythrocytosis, and it is important to consider not simply the absolute serum erythropoietin level but also the serum erythropoietin level relative to simultaneously measured hemoglobin level. We should include paraneoplastic erythrocytosis as a differential diagnosis in cases of high hemoglobin level unexplained by other diseases.

Topics: Adenocarcinoma; Aged; Colonic Neoplasms; Erythropoietin; Female; Humans; Paraneoplastic Syndromes; Polycythemia; Reference Values

It has been suggested that preoperative administration of erythropoietin (Epo) in patients with gastrointestinal cancer reduces transfusional needs and is also associated with lower morbidity. On the other hand, experimental and clinical studies show that Epo might enhance tumor growth and angiogenesis. Our aim was to ascertain whether preoperative administration of Epo has any effect on tumor recurrence after curative surgery using an experimental model of colon cancer.. We induced tumors by injecting B51LiM colon cancer cells into the cecal wall of Balb/c mice. We randomized the animals into three groups of treatment with (1) recombinant human Epo, (2) recombinant mouse Epo, or (3) vehicle alone, for 12 d until cecectomy. On postoperative day 12, we killed mice and analyzed tumor recurrence. We measured serum levels of vascular endothelial growth factor and determined vascular endothelial growth factor expression and tumor microvessel density by immunohistochemistry. We also investigated the in vitro effect of Epo on B51LiM cell line proliferation.. All three groups displayed tumor recurrence, but the final tumor load score and total tumoral weight were higher in the two groups that included Epo. The differences were statistically significant when we compared the recombinant mouse Epo group with the control group. We found no evidence of increased angiogenesis or enhanced cell proliferation as possible mechanisms of Epo-induced recurrence.. Preoperative administration of Epo stimulates tumor recurrence in an animal model of colon cancer. Our results point to the need for further research on the mechanisms of tumor growth enhancement by Epo, to better understand the benefits or disadvantages of Epo treatment.

Topics: Adenocarcinoma; Anemia; Animals; Cell Line, Tumor; Cell Proliferation; Colonic Neoplasms; Erythropoietin; Female; Mice; Mice, Inbred BALB C; Neoplasm Recurrence, Local; Neovascularization, Pathologic; Preoperative Care; Vascular Endothelial Growth Factor A

Topics: Colonic Neoplasms; Erythropoietin; Humans; Liver Neoplasms; Male; Middle Aged

Erythropoiesis-stimulating agents (erythropoietin and darbepoietin) have been approved to reduce the number of blood transfusions required during chemotherapy; however, concerns about the risks of venous thromboembolism and mortality exist.. We identified patients who were aged 65 years or older in the Surveillance, Epidemiology, and End Results-Medicare database; who were diagnosed with colon, non-small cell lung, or breast cancer or with diffuse large B-cell lymphoma from January 1, 1991, through December 31, 2002; and who received chemotherapy. The main outcome measures were claims for use of an erythropoiesis-stimulating agent, blood transfusion, venous thromboembolism (ie, deep vein thrombosis or pulmonary embolism), and overall survival. We used multivariable logistic regression models to analyze the association of erythropoiesis-stimulating agent use with clinical and demographic variables. We used time-dependent Cox proportional hazards models to analyze the association of time to receipt of first erythropoiesis-stimulating agent with venous thromboembolism and overall survival. All statistical tests were two-sided.. Among 56,210 patients treated with chemotherapy from 1991 through 2002, 15,346 (27%) received an erythropoiesis-stimulating agent. The proportion of patients receiving erythropoiesis-stimulating agents increased from 4.8% in 1991 to 45.9% in 2002 (P < .001). Use was associated with more recent diagnosis, younger age, urban residence, comorbidities, receipt of radiation therapy, female sex, and metastatic or recurrent cancer. The rate of blood transfusion per year during 1991-2002 remained constant at 22%. Venous thromboembolism developed in 1796 (14.3%) of the 12,522 patients who received erythropoiesis-stimulating agent and 3400 (9.8%) of the 34,820 patients who did not (hazard ratio = 1.93, 95% confidence interval = 1.79 to 2.07). Overall survival was similar in both groups.. Use of erythropoiesis-stimulating agent increased rapidly after its approval in 1991, but the blood transfusion rate did not change. Use of erythropoiesis-stimulating agents was associated with an increased risk of venous thromboembolism but not of mortality.

Topics: Aged; Aged, 80 and over; Analysis of Variance; Anemia; Antineoplastic Agents; Blood Transfusion; Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Colonic Neoplasms; Confounding Factors, Epidemiologic; Darbepoetin alfa; Erythropoietin; Female; Hematinics; Humans; Lung Neoplasms; Lymphoma, Large B-Cell, Diffuse; Male; Medical Record Linkage; Medicare; Neoplasms; Practice Patterns, Physicians'; Recombinant Proteins; Retrospective Studies; Risk Factors; SEER Program; United States; Venous Thromboembolism

Evaluation of the clinical efficacy and tolerance of metronomic chemotherapy as salvage therapy in a young patient with advanced, platinum resistant, ovarian carcinoma and bad performance status.. We tried palliative chemotherapy with daily low dose oral cyclophosphamide with a patient suffering from stage IIIC ovarian cancer that responded to daily cyclophosphamide (CTX) after no response to chemotherapy with paclitaxel and carboplatin as first line and progression after second line with topotecan. The progression-free survival time on daily low dose oral cyclophosphamide treatment was 65 months without side effects. She was well during the chemotherapy and lived a normal working and social life.. We think that use of low dose of oral CTX should be investigated further as a strategy against tumour progression after standard chemotherapy in patients who are platinum resistant with poor performance status.

Topics: Adult; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Colonic Neoplasms; Colostomy; Cyclophosphamide; Cystadenocarcinoma, Serous; Disease-Free Survival; Drug Administration Schedule; Drug Evaluation; Drug Resistance, Neoplasm; Epoetin Alfa; Erythropoietin; Fatal Outcome; Female; Follow-Up Studies; Hemorrhage; Humans; Intestinal Obstruction; Karnofsky Performance Status; Laparotomy; Ovarian Neoplasms; Ovariectomy; Paclitaxel; Palliative Care; Peritoneal Neoplasms; Recombinant Proteins; Salvage Therapy; Topotecan; Urinary Bladder Neoplasms; Vitamins

Tumour hypoxia has been shown to increase mutation rate, angiogenesis, and metastatic potential, and decrease response to conventional therapeutics. Improved tumour oxygenation should translate into increased treatment response. Exogenous recombinant erythropoietin (rEpo) has been recently shown to increase tumour oxygenation in a mammary carcinoma model. The mechanism of this action is not yet understood completely. The presence of Epo and its receptor (EpoR) have been demonstrated on several normal and neoplastic tissues, including blood vessels and various solid tumours. In addition, rEpo has been shown in two recent prospective, randomized clinical trials to negatively impact treatment outcome. In this study, we attempt to characterize the direct effects of rEpo on tumour growth and angiogenesis in two separate rodent carcinomas. The effect of rEpo on R3230 rat mammary adenocarcinomas, CT-26 mouse colon carcinomas, HCT-116 human colon carcinomas, and FaDu human head and neck tumours, all of which express EpoR, was examined. There were no differences in tumour growth or proliferation (measured by Ki-67) between placebo-treated and rEpo-treated tumours. In the mammary window chamber, vascular length density (VLD) measurements in serial images of both placebo-treated and Epo-treated rats revealed no difference in angiogenesis between the Epo-treated tumours and placebo-treated tumours at any time point. These experiments are important because they suggest that the recent clinical detriment seen with the use of Epo is not due to its tumour growth effects or angiogenesis. These studies also suggest that further preclinical studies need to examine rEpo's direct tumour effects in efforts to improve the therapeutic benefits of Epo in solid tumour patients.

Topics: Animals; Carcinoma; Cell Hypoxia; Cell Proliferation; Colonic Neoplasms; Erythropoietin; Head and Neck Neoplasms; Humans; Mammary Neoplasms, Animal; Mice; Neovascularization, Pathologic; Placebos; Random Allocation; Rats; Recombinant Proteins; Tumor Cells, Cultured

In cancer cachexia, erythropoietin often yields beneficial therapeutic effects by improving patient's metabolic and exercise capacity via an increased erythrocyte count. However, erythropoietin also has counter-regulatory effects against pro-inflammatory cytokines, which are postulated to be mediators of cancer cachexia. We investigated the mechanisms by which erythropoietin improves the cachectic condition. In this study, 100 Units/day of erythropoietin were administered intraperitoneally to BALB/c male mice, carrying a subclone of colon 26 adenocarcinoma, beginning on the day after tumor inoculation and continuing until they died. Erythropoietin administration attenuated the decline in body weight, as well as the decline in fat and muscle weights, of tumor-bearing mice, but improved the survival of cachectic mice. Mice receiving erythropoietin had increased erythrocyte and platelet counts, but significantly decreased white blood cell count. In addition, erythropoietin administration significantly decreased interleukin-6 levels, not only in serum but also in the inoculated tumor. These results indicate that the positive therapeutic effects of erythropoietin on cancer cachexia are due, not only to improving metabolic and exercise capacity via an increased erythrocyte count, but also to attenuation of cachectic manifestations by decreased production of the cachexia-inducing cytokine, interleukin-6.

Topics: Adenocarcinoma; Animals; Cachexia; Colonic Neoplasms; Cytokines; Disease Models, Animal; Down-Regulation; Eating; Erythropoietin; Interleukin-6; Liver; Male; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Spleen; Survival Rate

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

Gene therapy is a modality for the treatment of solid tumors that involves the introduction of a suicide gene into the tumor cells. Genetic radiotherapy involves the placement of a radiation-sensitive promoter upstream from a suicide gene. Because of their irregular vasculature some solid tumors are chronically hypoxic and hence are resistant to conventional treatment with chemotherapy and ionizing radiation (IR). The purpose of this study was to demonstrate that regional tumor hypoxia could be exploited to improve local tumor control. The cDNA coding the erythropoietin hypoxia-responsive element (EPO) was placed upstream from the Egr-TNF-alpha construct. WIDR human colon adenocarcinoma cells were injected into the right hind limb of nude mice and treated with Epo-Egr-TNF-alpha plasmid with or without IR. Tumor volumes were measured by calipers and tumor necrosis factor (TNF)-alpha content of the tumor was determined by enzyme-linked immunosorbent assay. Treatment with the combined regimen of Epo-Egr-TNF-alpha plasmid + IR resulted in significant tumor growth delay. Tumor TNF-alpha content was increased by 30 per cent in the combined treatment group compared with each treatment alone. Regional tumor hypoxia can be exploited successfully to induce tumor growth delay, enhance local control, and enhance the therapeutic ratio.

Topics: Adenocarcinoma; Animals; Cell Hypoxia; Colonic Neoplasms; Combined Modality Therapy; DNA-Binding Proteins; Early Growth Response Protein 1; Erythropoietin; Female; Gene Expression; Genetic Therapy; Genetic Vectors; Humans; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Immediate-Early Proteins; Mice; Mice, Nude; Neoplasm Transplantation; Nuclear Proteins; Oxygen; Plasmids; Transcription Factors; Transfection; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

Mitomycin C is a powerful antineoplastic agent. If used at high dosage, it may cause a secondary form of adult hemolytic-uremic syndrome (HUS). Blood transfusions worsen the evolution of this peculiar form of HUS. We describe a patient who developed HUS after treatment with mitomycin C (total dose 144 mg/m2) due to a carcinoma of the ascending colon. Repeated blood transfusions were associated with rapidly evolving renal failure coupled with anemia and thrombocytopenia. Haptoglobin was undetectable. Soon after starting subcutaneous erythropoietin, the velocity of progression of renal failure slowed whilst no more blood transfusions were required and haptoglobin levels returned to normal. Thereafter, the patient's renal function slowly worsened and she started chronic hemodialysis 5 years later. Up to now, all investigations have failed to show a relapse of her adenocarcinoma. A possible explanation of these data is that erythropoietin permitted the termination of blood transfusions which both triggered and perpetuated the syndrome. However, we cannot exclude a primitive effect of erythropoietin on the endothelium or on the platelets.

Topics: Antibiotics, Antineoplastic; Colonic Neoplasms; Erythropoietin; Female; Hemolytic-Uremic Syndrome; Humans; Middle Aged; Mitomycin

High-dose anticancer drugs have been shown to induce an increase in serum erythropoietin (sEpo) levels not mediated by hypoxia. In this study, sEpo was assessed in seven patients who had been administered a course of 5-day leucovorin-modulated 5-fluorouracil (5-FU-LV) as an adjuvant therapy after the removal of colon cancer. During this study, the mean hemoglobin (Hb) concentration stayed at a constant level, peripheral blood (PB) reticulocytes showed an early, sharp decline, and sEpo levels progressively increased for 15 days after the start of chemotherapy. These results appear to indicate that the increase in sEpo, which was not related to anemia, may have followed from the administration of a cytotoxic drug at doses used in routine, clinical practice.

Topics: Aged; Colonic Neoplasms; Erythropoiesis; Erythropoietin; Female; Fluorouracil; Humans; Leucovorin; Male; Middle Aged; Reticulocyte Count; Time Factors

Neoplasias, especially in their more advanced stages, are often associated with chronic anemia of malignancy which impairs the patient's physical ability and quality of life.. Forty-two patients with chronic anemia associated with hematological malignancies (18 multiple myelomas, 10 myelodysplastic syndromes) or solid tumors (9 breast cancers, 5 colon cancers) were treated with 150-300 units/kg rHuEPO for a median time period of 16 weeks. Response was defined as an increase of the initial hemoglobin level by at least 2 g/dl.. The response rates for solid tumors were comparable (44.4% and 40% for breast cancer and colon cancer, respectively), whilst the response in patients with hematological malignancies depended strongly on the disease entity (77.8% for multiple myeloma, 10% for myelodysplastic syndrome). Pretreatment serum levels of endogenous erythropoietin (EPO) were significantly higher in non-responding patients than in responders. During rHuEPO therapy, EPO levels in non-responders increased even further, while they remained basically unchanged in responding patients. In responders, the WHO performance status before the start of rHuEPO therapy was more favorable and showed impressive improvement during the course of treatment. The median survival time of responders was 28.0 months as compared to only 9.2 months for non-responders. Clinical symptoms of anemia subsided or at least considerably improved under successful rHuEPO therapy. With the exception of occasional flu-like symptoms, no undesirable effects of rHuEPO treatment were observed.. In conclusion, rHuEPO treatment corrected anemia of malignancy both in patients with hematologic disease and in those with solid tumors, but responsiveness varied considerably amongst the different disease entities.

Topics: Aged; Aged, 80 and over; Anemia; Breast Neoplasms; Chronic Disease; Colonic Neoplasms; Erythropoietin; Female; Hemoglobins; Humans; Male; Middle Aged; Multiple Myeloma; Myelodysplastic Syndromes; Survival Rate; Treatment Outcome