epoetin-alfa and Adenocarcinoma

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

This prospective, nonrandomized study evaluates the effectiveness of epoetin alfa to maintain the hemoglobin levels at 12 to 14 g/dL (optimal range for tumor oxygenation) during chemoradiation for Stage III esophageal cancer and its impact on overall survival (OS), metastatic-free survival (MFS), and locoregional control (LC).. Ninety-six patients were included. Forty-two patients received epoetin alfa (150 IU/kg, 3 times a week) during radiotherapy, which was started at hemoglobin less than 13 g/dL and stopped at 14 g/dL or higher. Hemoglobin levels were measured weekly during RT.. Both groups were balanced for age, sex, performance status, tumor length/location, histology, grading, T-stage/N-stage, chemotherapy, treatment schedule, and hemoglobin before RT. Median change of hemoglobin was +0.3 g/dL/wk with epoetin alfa and -0.5 g/dL/wk without epoetin alfa. At least 60% of hemoglobin levels were 12 to 14 g/dL in 64% and 17% of the patients, respectively (p < 0.001). Patients who received epoetin alfa had better OS (32% vs. 8% at 2 years, p = 0.009) and LC (67% vs. 15% at 2 years, p = 0.001). MFS was not significantly different (42% vs. 18% at 2 years, p = 0.09).. The findings suggest that epoetin alfa when used to maintain the hemoglobin levels at 12 to 14 g/dL can improve OS and LC of Stage III esophageal cancer patients.

Topics: Adenocarcinoma; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Disease-Free Survival; Epoetin Alfa; Erythropoietin; Esophageal Neoplasms; Female; Fluorouracil; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Proportional Hazards Models; Prospective Studies; Radiotherapy Dosage; Recombinant Proteins

In a previous study we showed that many patients with esophagogastric adenocarcinoma experience anemia during neoadjuvant chemotherapy. We now investigated the role of erythropoietin in managing anemia during neoadjuvant chemotherapy.. Patients with esophagogastric adenocarcinoma who experienced anemia (hemoglobin < 12 g/dL) during neoadjuvant treatment received erythropoietin 10,000 IE subcutaneously three times a week. Primary outcomes were the response to erythropoietin, safety, the need for allogeneic red blood cell transfusion, and the rate of postoperative complications.. Between April 2003 and December 2004, 24 patients (median age, 62 years) were enrolled. The mean hemoglobin level before chemotherapy was 12.5 g/dL and the mean hemoglobin level before patients received erythropoietin was 11.5 g/dL. One year after involvement in the trial, 4 of 17 analyzable patients were still anemic (hemoglobin level < 12 mg/dL). Twenty-two patients received erythropoietin, and 16 (73%) responded. We could observe a significant increase in hemoglobin concentrations under therapy with erythropoietin to 12.6 g/dL (p < 0.001). Two patients (8%) received allogeneic transfusions; the rate of postoperative complications was 16%. There were no erythropoietin-related adverse events.. Treatment with erythropoietin is effective and well tolerated in patients with esophagogastric adenocarcinoma who experience anemia during neoadjuvant chemotherapy.

Topics: Adenocarcinoma; Aged; Anastomosis, Surgical; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Cisplatin; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Female; Fluorouracil; Gastrectomy; Hemoglobins; Humans; Leucovorin; Male; Middle Aged; Neoadjuvant Therapy; Organoplatinum Compounds; Oxaliplatin; Paclitaxel; Postoperative Complications; Prospective Studies; Recombinant Proteins; Stomach Neoplasms; Survival Analysis

Results of treatment of 39 patients, to whom pancreatoduodenal resection was performed for periampullar zone tumour, were analyzed. Anemia, revealed before the operation, had constituted the factor, which trustworthily increased the postoperative complications occurrence risk. Therapeutic course, using recombinant erythropoietins, was conducted for correction of anemia in 7 patients. This had promoted the hemoglobin level raising, the risk of postoperative complications occurrence lowering, but did not influence the intraoperative blood loss severity and perioperative hemotransfusion volume.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Anemia; Bile Duct Neoplasms; Digestive System Neoplasms; Drug Administration Schedule; Duodenal Neoplasms; Epoetin Alfa; Erythropoietin; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Pancreaticoduodenectomy; Postoperative Complications; Recombinant Proteins; Risk Factors; Treatment Outcome

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

Erythropoietin (Epo) is a key regulator of erythroid cell proliferation, differentiation and apoptosis. In the form of the recombinant protein, it is widely used to treat various types of anemias, including that associated with cancer and with the myelosuppressive effects of chemotherapy, particularly platinum-based regimens. Our previous studies confirmed the presence of Epo receptors (EpoRs) in ovarian adenocarcinoma cell lines and demonstrated that long-term Epo treatment of A2780 cells resulted in the development of a phenotype exhibiting both enhanced Epo signaling and increased paclitaxel resistance. In the present study, we carried out a series of experiments to analyze the pro-angiogenic potential of Epo-treated A2780 and SKOV-3 cells. Our studies revealed that conditioned media of Epo-treated A2780 cells had a stimulative effect on human umbilical vein endothelial cells (HUVECs). This effect was only seen when A2780 cells were incubated under hypoxic conditions. Furthermore, Epo increased the secretion of interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, GM-CSF and interferon-γ by A2780 cells that grew in hypoxic conditions. In this regard, conditioned media of hypoxic and Epo-treated A2780 cells induced a significant phosphorylation of STAT-5 in HUVECs. Our results may have important implications for ovarian cancer patients receiving Epo.

Topics: Adenocarcinoma; Blotting, Western; Cell Proliferation; Culture Media, Conditioned; Enzyme-Linked Immunosorbent Assay; Epoetin Alfa; Erythropoietin; Female; Human Umbilical Vein Endothelial Cells; Humans; Hypoxia; Neovascularization, Pathologic; Ovarian Neoplasms; Real-Time Polymerase Chain Reaction; Recombinant Proteins; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Tumor Cells, Cultured

In a large, 16-week, prospective study of 2,964 anemic patients with various cancers undergoing chemotherapy, once-weekly subcutaneous administration of 40,000 U of epoetin alfa,with potential escalation to 60,000 U, increased hemoglobin (Hgb) levels, decreased transfusion requirements, and improved quality of life (QOL) as assessed using the Linear Analog Scale Assessment (LASA) for energy, activity, and overall QOL and the Functional Assessment in Cancer Therapy-Anemia (FACT-An) QOL instrument. A retrospective subset analysis conducted in 244 colorectal cancer patients enrolled in the study showed statistically significant improvements from baseline to final readings in LASA energy, activity, and overall QOL and FACT-An Anemia Symptoms and Fatigue subscale scores (P < 0.02). Moreover, patients who achieved larger improvements in Hgb levels also demonstrated greater percentage improvements in QOL over baseline measurements. Mean Hgb levels increased by 1.2 g/dL after 4 weeks of treatment and by 1.6 g/dL by study end, independent of red blood cell transfusion within 28 days prior to the Hgb assessment. Hematopoietic response (Hgb level > or = 12 g/dL and/or increase in Hgb level > or = 2 g/dL, independent of transfusion) was observed in 61% of patients (139/229). Additionally, the proportion of patients receiving transfusions decreased from 17% at baseline to 4% during the final month of therapy. Epoetin alfa was well tolerated, with no evidence of unexpected adverse events. Except for significantly higher QOL scores at baseline, results for the cohort of colorectal cancer patients were similar to those for patients with other cancer types in the main study population.

Topics: Adenocarcinoma; Adult; Anemia; Antineoplastic Agents; Clinical Trials as Topic; Colorectal Neoplasms; Epoetin Alfa; Erythropoietin; Fatigue; Hemoglobins; Humans; Quality of Life; Recombinant Proteins; Retrospective Studies

It has been suggested that hemoglobin levels of 12-14 g/dL are optimal for tumor oxygenation, radiosensitivity, and prognosis. In this prospective study, the authors evaluated the effectiveness of epoetin-alpha to maintain hemoglobin levels at 12-14 g/dL during radiotherapy (RT) for patients with UICC Stage III esophageal carcinoma, and they examined the impact of erythropoetin on overall survival (OS), metastatic-free survival (MFS), and local control (LC).. Sixty patients who received RT between March, 2001 and September, 2004, were included in this prospective, nonrandomized study. Thirty patients received epoetin-alpha (150 IU/kg 3 times per week) during RT (Group A), and 30 patients did not receive epoetin-alpha (Group B). Epoetin-alpha was started at hemoglobin levels < 13 g/dL and was stopped at hemoglobin levels > or = 14 g/dL. Hemoglobin was measured before RT and once weekly during RT.. Both patient groups were balanced for age, gender, performance status, tumor location/length, histology, grading, tumor classification, lymph node status, chemotherapy, treatment (45-50.4 grays [Gy] plus resection vs. 45.0-50.4 Gy vs. 59.4-66.0 Gy), and hemoglobin level before RT. In 20 of 30 patients (67%) from Group A and in 3 of 30 patients (10%) from Group B, > or = 60% of hemoglobin levels during RT were 12-14 g/dL (P = 0.003). The median change in hemoglobin was + 0.4 g/dL per week in Group A and - 0.4 g/dL per week in Group B. LC was significantly better in Group A (66% vs. 38% at 1 year, respectively; P = 0.012), a trend was observed for OS (59% vs. 33%, respectively; P = 0.08), and MFS did not differ significantly (43% vs. 38%, respectively; P = 0.34). No epoetin-alpha-related toxicity was observed.. Epoetin-alpha was effective in maintaining the hemoglobin levels at 12-14 g/dL during RT. The application of epoetin-alpha significantly improved LC, and a trend was observed for OS.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; Combined Modality Therapy; Drug Therapy, Combination; Epoetin Alfa; Erythropoietin; Esophageal Neoplasms; Female; Gamma Rays; Hematinics; Hemoglobins; Humans; Male; Middle Aged; Prospective Studies; Recombinant Proteins; Survival Rate

Within hypoxic tumor regions anaerobic dissimilation of glucose is the sole source of energy generation. It yields only 5% of the ATP that is normally gained by means of oxidative glucose catabolism. The increased need for glucose may aggravate cancer cachexia. We investigated the impact of recombinant human erythropoietin (RhEPO) and increased inspiratory oxygen concentrations on weight loss in tumor-bearing mice.. Fragments of the murine C26-B adenocarcinoma were implanted in 60 BALB/c-mice. The mice were divided into four groups and assigned to: (A) no treatment; (B) RhEPO- administration (25 IU daily from day 1-11, three times per week from day 12); (C) RhEPO and 25% oxygen; and (D) RhEPO and 35% oxygen. Three control groups of four healthy mice each received the same treatment as groups A, B, and D, respectively. Hematocrit and hemoglobin levels, tumor volume, and body weight were monitored. At day 17 the experiment was terminated and the serum lactate concentration was measured. The tumors were excised and weighed and, for each mouse, the percentage weight loss was calculated. The impact of tumor weight and the treatments on lactate concentration and weight loss was evaluated.. Significant positive correlations were found between tumor weight and lactate concentration and between tumor weight and percentage weight loss. In the mice with the largest tumors, RhEPO displayed a significant weight loss-reducing effect, and a significant negative correlation was found between hemoglobin concentration and weight loss. An oxygen-rich environment did not appear to influence weight loss.. Anaerobic glycolysis in a growing C26-B tumor is related to weight loss. RhEPO administration results in a reduction of the percentage weight loss; this effect is probably mediated by an increased hemoglobin concentration.

Topics: Adenocarcinoma; Animals; Cachexia; Disease Models, Animal; Epoetin Alfa; Erythropoietin; Glycolysis; Hematocrit; Hemoglobins; Inhalation; Mice; Mice, Inbred BALB C; Oxygen; Recombinant Proteins; Weight Loss

Topics: Adenocarcinoma; Animals; Blood; Carcinoma; Carcinoma, Hepatocellular; Epoetin Alfa; Erythropoietin; Growth Substances; Humans; Iron; Iron Isotopes; Liver Extracts; Liver Neoplasms; Liver Neoplasms, Experimental; Lymphoma; Neoplasms; Neoplasms, Experimental; Radiometry; Rats

Topics: Adenocarcinoma; Blood Cell Count; Carcinoma, Renal Cell; Epoetin Alfa; Erythropoietin; Geriatrics; Humans; Kidney Neoplasms; Lung Neoplasms; Mercaptopurine; Neoplasm Metastasis; Neoplasms; Neoplasms, Second Primary; Nephrectomy

Topics: Adenocarcinoma; Blood; Body Fluids; Carcinoma, Renal Cell; Epoetin Alfa; Erythrocytes; Erythropoiesis; Erythropoietin; Humans; Kidney Neoplasms; Neoplasm Metastasis; Nephrectomy; Pathology; Polycythemia; Urine

Topics: Adenocarcinoma; Bone Marrow Examination; Carcinoma, Renal Cell; Epoetin Alfa; Erythrocytes; Erythropoiesis; Erythropoietin; Hematocrit; Kidney Neoplasms; Polycythemia; Rats; Research; Tissue Extracts