losartan-potassium and Carcinoma--Small-Cell

Anemia is common among patients with malignant tumors, due to the disease and chemotherapy. Active oncotherapy, combination chemotherapy of lung cancer is accompanied with many side effects which may impair the patient's quality of life and compromise the effectiveness of chemotherapy, the most frequent one of them being chemotherapy-induced anemia. Anemia decreases not only the patient's quality of life, but also worsens the dose-intensity of chemotherapy. One of the potential treatments of chemotherapy-induced anemia is erythropoietin-stimulating agents (ESAs) for the appropriate indications. Several national and international studies have shown that ESA therapy effectively increases hemoglobin level. However, more recently, contradictory results were published on ESA treatment in terms of survival and tumor progression. The reason for this may be that the tumor cells and endothelial cells may as well express erythropoietin receptor, the role of which has not yet been fully elucidated in tumor progression.. Daganatos betegek körében gyakori szövõdmény az anémia, amelyet maga a betegség vagy az onkológiai kezelés okozhat. A tüdõrák kezelése során az aktív kombinált kemoterápia mellett számos, a beteg életminõségét és az onkoterápia sikerességét rontó mellékhatással kell számolni, ezek közül az egyik leggyakoribb a kemoterápia indukálta anémia. A vérszegénység nemcsak a betegek életminõségét rontja, hanem a citotoxikus kezelés dóziscsökkentéséhez, illetve késleltetéséhez vezethet. A kemoterápia indukálta anémia kezelésének egyik lehetséges útja, az eritropoetin-stimuláló szerek (ESA) használata a megfelelõ indikációval. Számos nemzetközi és hazai tanulmány bizonyította, hogy az ESA-kezelés hatékonyan emeli a hemoglobinszintet. Az utóbbi idõben azonban ellentmondásos eredményeket olvashattunk az ESA-kezelésrõl a túlélés és a daganat progressziója tekintetében. Ennek a hátterében az állhat, hogy a tumorsejtek és az endothelsejtek is kifejezhetnek eritropoetinreceptort, amelynek a szerepe még nem teljesen tisztázott a daganatok progressziójában.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Disease Progression; Endothelial Cells; Erythrocyte Transfusion; Erythropoietin; Hematinics; Hemoglobins; Humans; Hypertension; Lung Neoplasms; Quality of Life; Receptors, Erythropoietin; Severity of Illness Index; Venous Thromboembolism

Topics: Anemia, Hypochromic; Antineoplastic Agents; Breast Neoplasms; Carcinoma, Small Cell; Clinical Protocols; Darbepoetin alfa; Data Interpretation, Statistical; Erythropoietin; Female; Filgrastim; Follow-Up Studies; Graft vs Host Disease; Granulocyte Colony-Stimulating Factor; Granulocytes; Hematinics; Hematologic Neoplasms; Hematopoietic Cell Growth Factors; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins, Intravenous; Lung Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin; Male; Multicenter Studies as Topic; Neoplasms; Neutropenia; Platelet Aggregation Inhibitors; Polycythemia Vera; Polyethylene Glycols; Randomized Controlled Trials as Topic; Recombinant Proteins; Research Design; Survival Analysis; Thrombocythemia, Essential; Treatment Outcome

The purpose was to conduct an integrated analysis of the cumulative hematologic toxicity of topotecan in patients with relapsed ovarian cancer and small cell lung cancer (SCLC). Data were pooled from eight phase II and phase III clinical studies performed in patients with relapsed stage III/IV ovarian cancer or extensive SCLC treated with topotecan at a dose of 1.5 mg/m(2) per day on days 1-5 of a 21-day course. Quantitative hematologic toxicities were assessed using the National Cancer Institute Common Toxicity Criteria. A total of 4,124 courses of therapy was administered to the 879 patients in the pooled population. Grade 4 neutropenia was experienced by 78% of patients. The lowest nadirs for neutrophils and platelets generally occurred after the first course of therapy, followed by improvement or stabilization in subsequent courses. Neutropenia was noncumulative. During the first course, significant risk factors were identified: renal impairment and advanced age (grade 3/4 thrombocytopenia and grade 4 neutropenia) and prior radiotherapy; performance status score > or =2; SCLC; and exposure to both cisplatin (Platinol; Bristol-Myers Squibb, Princeton, NJ, http://www.bms.com) and carboplatin (Paraplatin; Bristol-Myers Squibb) (grade 3/4 thrombocytopenia only). The most frequent interventions for hematologic toxicities were RBC transfusions, treatment delays, G-CSF support, and dose reductions. Analysis of neutrophil and platelet nadirs and dosing for each course of therapy showed no apparent evidence of cumulative neutropenia or thrombocytopenia. The risk of grade 3 or 4 anemia was higher during the first four courses of therapy and may need to be more aggressively managed with erythropoietin therapy.

Topics: Antineoplastic Agents; Bone Marrow; Carcinoma, Small Cell; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Neutropenia; Ovarian Neoplasms; Topotecan

Recent meta-analysis of patients with small cell lung cancer has confirmed the effectiveness of prophylactic cranial irradiation in reducing the cumulative incidence of brain metastases and contributing to a significant increase in 3-year survival. Likewise, with increased median survivals being documented in patients with stage IIIA/B non-small cell lung cancer, there is evidence that the brain is emerging as a significant metastatic target site. Although prophylactic cranial irradiation is a reasonable option to explore, the potential for long-term neuropsychologic adverse effects is of concern in both diagnostic groups. Radiation-induced reactive oxygen intermediates and reactive nitrogen intermediates appear to play a major role in mediating this toxicity. Hypoxic stress results in a significant increase in erythropoietin (EPO) mRNA in mouse brain and, in two models, the administration of EPO improves performance function and prevents cognitive impairment. With the demonstration of EPO receptors in astrocytes, neurons, and brain capillary endothelial cells as well as the ability of EPO to cross the blood-brain barrier, a potential for EPO-mediated central nervous system radioprotection is postulated. The rationale and preliminary design for a phase III study of EPO as a neurocognitive protectant in patients with lung cancer receiving prophylactic cranial irradiation is presented.

Topics: Animals; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Cell Hypoxia; Clinical Trials, Phase III as Topic; Cognition; Cranial Irradiation; Cytoprotection; Drug Evaluation, Preclinical; Erythropoietin; Humans; Lung Neoplasms; Neuroprotective Agents; Reactive Nitrogen Species; Reactive Oxygen Species; Signal Transduction

Darbepoietin-alpha is a novel erythropoiesis-stimulating protein that may help address some of the unmet needs of anemia treatment in patients with cancer. Compared with recombinant human erythropoietin, darbepoietin-alpha has increased sialylated carbohydrate content, associated with a prolonged serum half-life and increased in vivo biologic activity. Data from trials in patients with cancer with a range of tumor types, whether receiving chemotherapy or not, indicate that darbepoietin-alpha is effective in alleviating anemia when dosed at intervals of once every 1, 2, or 3 weeks and may effect greater and more rapid responses than recombinant human erythropoietin. Health-related quality of life benefits have been observed with darbepoietin-alpha treatment, and in a study of patients with small-cell lung cancer, darbepoietin-alpha was associated with increased progression-free survival. Administration of darbepoietin-alpha at extended dosing intervals offers the possibility of enhanced patient convenience and compliance and a reduced burden on healthcare resources. Confirmation of improved response and response times with this novel therapy may enable patients with cancer to benefit more rapidly.

Topics: Carcinoma, Small Cell; Darbepoetin alfa; Disease-Free Survival; Erythropoiesis; Erythropoietin; Humans; Lung Neoplasms; Neoplasms

Topics: Adrenocorticotropic Hormone; Bronchial Neoplasms; Calcitonin; Carcinoma, Small Cell; Erythropoietin; Fluorescent Antibody Technique; Gastrointestinal Hormones; Gonadotropins, Pituitary; Growth Hormone; Histocytochemistry; Hormones, Ectopic; Humans; Hypercalcemia; Insulin; Insulin Secretion; Neoplasm Metastasis; Neurophysins; Oxytocin; Paraneoplastic Endocrine Syndromes; Parathyroid Hormone; Placental Lactogen; Prolactin; Thyrotropin; Vasopressins

The purpose of the current study was to investigate the role of amifostine and epoetin-alpha in reducing severe toxicities during concurrent chemo-hyperfractionated radiotherapy (CCRT) for limited disease small cell lung cancer (LD-SCLC).. Seventy-six patients with LD-SCLC were enrolled. The treatment schedule was consisted of two 28-day cycles of cisplatin at a dose of 30 mg/m2 (Days 1 and 8) and irinotecan at a dose of 60 mg/m2 (Days 1, 8, and 15) followed by two 21-day cycles of cisplatin at a dose of 60 mg/m2 (Day 1) and etoposide at a dose of 100 mg/m2 (Days 1-3) with concurrent twice-daily thoracic radiotherapy for a total of 45 grays. Patients were randomly assigned at registration to either amifostine at a dose of 500 mg or epoetin-alpha at a dose of 10,000 IU subcutaneously 3 times weekly (n = 36 patients and 40 patients, respectively). Fifteen of 36 patients assigned to the amifostine arm did not receive amifostine because of a lack of supply.. Amifostine treatment was associated with higher febrile neutropenia (P = .003) and grade 2 or 3 nausea (according to the National Cancer Institute Common Toxicity Criteria [version 3.0]) (P = .03). It also demonstrated a trend toward higher grade 4 leukopenia (P = .05). Grade 3 esophagitis was reported in 30% of patients treated with amifostine and 9% of patients treated with epoetin-alpha (P = .059). Epoetin-alpha treatment was associated with less grade 2 or 3 anemia (P = .031) and lower decreases in hemoglobin level during CCRT (P = .016). The median survival times for both treatment arms were comparable (22.6 months in the amifostine arm vs 25.6 months in the epoetin-alpha arm; P = .447).. Although amifostine administered 3 times weekly during CCRT did not significantly reduce severe toxicities, epoetin-alpha was effective in preventing severe anemia during CCRT in patients with LD-SCLC. Other radioprotective strategies to minimize severe toxicities should be investigated.

Topics: Aged; Amifostine; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Combined Modality Therapy; Dose Fractionation, Radiation; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Humans; Injections, Subcutaneous; Lung Neoplasms; Male; Middle Aged; Radiation-Protective Agents; Recombinant Proteins; Survival Analysis

The NeoPrevent study showed that early intervention with epoetin beta could prevent severe anaemia in patients with solid tumours receiving platinum-based chemotherapy. An early intervention strategy may be particularly warranted in patients with lung cancer, as anaemia is very common in these patients and can be severe. The purpose of this study was to examine the efficacy and safety of epoetin beta in the subpopulation of patients with lung cancer included in the NeoPrevent study. Patients were enrolled if baseline haemoglobin (Hb) levels were 1g/dl) plus the proportion whose Hb was maintained at +/-1g/dl of baseline. Quality of life (QoL) was measured using the linear analogue scale assessment. The NeoPrevent study included 255 patients in total, and the results for the 102 patients with lung cancer (non-small-cell lung cancer 64%; small-cell lung cancer 36%) are presented here. The overall anaemia prevention response was 90%, with Hb response in 60% of patients and maintenance of baseline Hb level in 30%. Only 9% of patients required transfusions. QoL improved significantly in patients with Hb response (p<0.01) and was maintained in non-responders (p>or=0.578). Epoetin beta was effective in preventing severe anaemia in lung cancer patients receiving platinum-based chemotherapy.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Disease Progression; Dose-Response Relationship, Drug; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Injections, Subcutaneous; Lung Neoplasms; Male; Middle Aged; Platinum Compounds; Recombinant Proteins; Severity of Illness Index; Time Factors; Treatment Outcome

A placebo-controlled, double-blind, randomized, phase III study was conducted in patients with extensive-stage small-cell lung cancer receiving first-line platinum-containing chemotherapy to determine if increasing or maintaining hemoglobin concentration with darbepoetin alpha could increase patient survival.. Darbepoetin alpha (300 microg) or placebo was administered once per week for 4 weeks then every 3 weeks for up to six cycles of chemotherapy (carboplatin plus etoposide or cisplatin plus etoposide) plus 3 weeks after the last dose of chemotherapy. Patients with disease progression were observed until death or until all patients completed their end-of-study visit and 496 deaths had occurred. The two coprimary end points were change in hemoglobin concentration from baseline to the end of the chemotherapy period and overall survival; statistical testing of survival was done if change in hemoglobin was significant at P < .05.. The study enrolled 600 patients. Patients' hemoglobin levels dropped due to the myelosuppressive chemotherapy; however, treatment with darbepoetin alpha maintained hemoglobin levels significantly higher than placebo (P < .001). There was no statistically significant difference in overall survival between the treatment groups (hazard ratio [HR], 0.93; 95% CI, 0.78 to 1.11; P = .431). As expected, darbepoetin alpha was associated with a higher incidence of thromboembolic events (darbepoetin alpha, 9%; placebo, 5%). The transfusion risk was lower in the darbepoetin versus placebo group (HR, 0.40; 95% CI, 0.29 to 0.55).. The results of this study did not demonstrate improved survival after treatment with darbepoetin alpha; however, they reinforce the benefit of erythropoiesis-stimulating agents in reducing transfusions and their neutral impact on survival in patients with chemotherapy-induced anemia.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Small Cell; Cisplatin; Darbepoetin alfa; Double-Blind Method; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Survival Rate

This randomized, double-blind, placebo-controlled trial (N93-004) evaluated the effects of epoetin alfa on tumor response to chemotherapy and survival in patients with small-cell lung cancer (SCLC).. Adult patients with hemoglobin < or = 14.5 g/dL starting chemotherapy received epoetin alfa 150 U/kg or placebo subcutaneously 3 times weekly until 3 weeks after completion of chemotherapy. Survival was assessed for 3 years. The primary end point was the proportion of patients with complete or partial response after three chemotherapy cycles.. The trial was terminated prematurely after 224 of a projected 400 patients were accrued. Baseline characteristics were similar between groups. Epoetin alfa and placebo patients (n = 109 and n = 115, respectively) had mean baseline hemoglobin of 12.8 g/dL and 13.0 g/dL, respectively. Overall tumor response was similar between the epoetin alfa and placebo groups after three chemotherapy cycles (72% and 67%, respectively; 95% CI of difference, -6% to 18%) and after completion of chemotherapy (60% and 56%, respectively; 95% CI of difference, -9% to 17%). Epoetin alfa and placebo groups had similar median overall survival (10.5 and 10.4 months, respectively) and overall mortality (91.7% and 87.8%, respectively; hazard ratio, 1.172; 95% CI, 0.887 to 1.549; P = .264). Hemoglobin was maintained in the prechemotherapy range in epoetin alfa patients, but decreased substantially in placebo patients. Fewer epoetin alfa patients than placebo patients required transfusion.. These results suggest that in newly diagnosed patients with SCLC epoetin alfa does not affect tumor response to chemotherapy or survival. However, the early trial closure makes these conclusions preliminary.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Double-Blind Method; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Lung Neoplasms; Middle Aged; Placebos; Recombinant Proteins; Survival Analysis

Currently, there is some debate concerning the haemoglobin level at which treatment of anaemia with erythropoiesis-stimulating agents should be initiated in cancer patients on chemotherapy. We report several analyses of data from a phase III trial of darbepoetin alfa versus placebo, comparing outcomes for patients with mild and moderate-to-severe anaemia.. Data were obtained from a phase III trial of darbepoetin alfa versus placebo in anaemic patients with lung cancer receiving chemotherapy ( n=314). Outcomes were compared for patients with baseline haemoglobin > or =10-11 g/dl and <10 g/dl.. Darbepoetin alfa significantly reduced transfusions compared with placebo, irrespective of haemoglobin level at treatment initiation. For patients with baseline haemoglobin <10 g/dl, 31% and 59% of those receiving darbepoetin alfa and placebo, respectively, required a transfusion from week 5 to the end of the treatment phase ( P<0.038). For patients with baseline haemoglobin > or =10 g/dl, the proportions were 15% and 41%, respectively ( P<0.001). Darbepoetin alfa also improved fatigue compared with placebo in both haemoglobin categories.. These findings show that initiating treatment at haemoglobin levels both <10 g/dl and > or =10-11 g/dl results in substantial clinical benefits, supporting the use of erythropoietic therapy also in patients with mild anaemia.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Chi-Square Distribution; Darbepoetin alfa; Erythrocyte Transfusion; Erythropoietin; Fatigue; Female; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Placebos; Retrospective Studies; Treatment Outcome

Non-small cell lung cancer (NSCLC) treatment with new drugs in combination with platinum salts induce anemia G1/2 and G3/4 WHO in about 35 and 10-20% of patients, respectively, with a chemotherapy (CT) dose intensity decrease in 20% of cases. Epoetin alfa, administered at standard dosages has been shown to significantly increase hemoglobin (Hb) levels, decrease transfusion requirements, and improve quality-of-life parameters in patients undergoing chemotherapy.. This open-label, non-randomized study was conducted to evaluate the efficacy and safety of an induction dose of epoetin alfa 40.000 IU in lung cancer patients with moderate or severe anemia who were receiving CT.. Twenty-four patients (8 SCLC and 16 NSCLC) were enrolled in the study to receive single subcutaneous (s.c.) injections of epoetin alfa 40.000 IU on days 1, 4, 7, 10, and 13, followed by standard treatment (10.000 IU t.i.w.) for the further 2 weeks. Nine patients had been previously treated with epoetin alfa 10.000 IU t.i.w. Twenty-two patients were receiving first-line CT and two patients were receiving docetaxel as second-line CT.. After 15 days of treatment, in 21 evaluable patients, Hb was 10.5 +/- 1.3 g/dL (mean +/- S.D.), with a mean increase from baseline of 2.0 g/dL (95%CI: 1.3-2.7). Hb increase was > or =2g/dL in 11 patients, 1-1.9 g/dL in 5 patients, and <1g/dL in 5 patients. After 30 days of treatment, Hb was 11.5 +/- 0.8 g/dL (mean +/- S.D.), with a mean increase from baseline of 2.9 g/dL (95%CI: 2.4-3.4) in 20 evaluable patients. No adverse events possibly related to epoetin alfa treatment were observed.. An induction therapy with epoetin alfa 40.000 IU for 2 weeks followed by standard treatment allows an Hb increase of 2.9 g/dL even in advanced lung cancer patients with a moderate/severe anemia, without RBC transfusion requirements. A randomized study of the proposed induction dose of epoetin alfa 40.000 IU is actually ongoing.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Intravenous; Lung Neoplasms; Male; Middle Aged; Recombinant Proteins; Treatment Outcome

Anaemia commonly occurs in cancer patients receiving chemotherapy, often necessitating blood transfusion. This multicentre study was designed to evaluate the efficacy and safety of epoetin alpha in preventing the decline in haemoglobin (Hb) level, and to determine whether the transfusion requirement could be reduced, in patients receiving 4-6 cycles of primarily platinum-based combination cyclic chemotherapy for small cell lung cancer (SCLC). A total of 130 non-anaemic SCLC patients were randomized to receive no additional treatment (n = 44), epoetin alpha 150 IU kg(-1) subcutaneously (s.c.) three times a week (n = 42) or 300 IU kg(-1) s.c. three times a week (n = 44). Reductions in epoetin alpha dosage were made during the study if Hb level increased to >15 g dl(-1). The mean weekly dosage was 335 and 612 IU kg(-1), respectively, in the two active treatment groups. Significantly fewer (P < 0.05) epoetin alpha-treated patients experienced anaemia (Hb < 10 g dl(-1)) during the course of chemotherapy (300 IU kg(-1), 39%; 150 IU kg(-1), 48%; untreated, 66%). This was reflected in the significantly lower number of treated patients transfused [300 IU kg(-1), 20% (P< 0.001); 150 IU kg(-1), 45% (P< 0.05); untreated, 59%]. Epoetin alpha was well-tolerated, and there was no evidence of sustained, clinically significant, hypertension. In summary, epoetin alpha is effective and well-tolerated in maintaining Hb level and reducing transfusion requirement in patients undergoing cyclic chemotherapy for SCLC.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Small Cell; Cisplatin; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Quality of Life; Recombinant Proteins

Recombinant human erythropoietin (r-Hu-EPO) is known to be effective in untreated cancer patients. Here we assess the possibility that r-Hu-EPO may also prevent or reduce anemia in patients who receive cytotoxic chemotherapy.. Thirty-six patients with small-cell lung carcinoma (SCLC) were enrolled onto a three-arm, randomized trial to investigate the effect of r-Hu-EPO on hemoglobin (Hb) levels and RBC and platelet (Plt) transfusions during chemotherapy. Bone marrow progenitors were studied before and after treatment. Two groups of patients received r-Hu-EPO at a dose of either 150 IU/kg (group 150) or 300 IU/kg (group 300) three times per week for the duration of chemotherapy. A control group did not receive r-Hu-EPO (group O). A maximum of six cycles of a chemotherapy regimen that consisted of vincristine, ifosfamide, carboplatin, and etoposide (VICE) were given to all patients. Hematologic parameters were measured weekly, and RBC or Plt transfusions were given for Hb levels less than 9 g/dL and Plt counts less than 20 x 10(9)/L.. Hb levels decreased in all patients, but onset of anemia was delayed in groups that received r-Hu-EPO (P = .002). A total of 116 U RBC were transfused in group 0, 54 in group 150, and 52 in group 300 (P = .017). In addition, there was a nonsignificant trend toward higher Plt counts and fewer Plt transfusions in patients who received r-Hu-EPO.. r-Hu-EPO at a dose of either 150 or 300 IU/kg three times weekly delays the onset of anemia and reduces RBC transfusion requirements in patients who undergo intensive chemotherapy for SCLC. A possible effect of r-Hu-EPO on platelet numbers deserves further study.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Small Cell; Colony-Forming Units Assay; Drug Administration Schedule; Erythrocyte Transfusion; Erythropoietin; Etoposide; Female; Granulocytes; Hemoglobin A; Humans; Ifosfamide; Iron; Leukocyte Count; Lung Neoplasms; Macrophages; Male; Mesna; Middle Aged; Platelet Count; Platelet Transfusion; Recombinant Proteins; Vincristine

Anemia is common among patients with malignant tumors, due to the disease and chemotherapy. Anemia decreases patient's quality of life, and worsens the dose intensity of chemotherapy. The aim of this retrospective data-analysis was to determine the rate of transfusions and the maintenance of chemotherapeutic dose intensity in 9 small cell lung cancer patients receiving beta-erythropoietin, due to anemia observed after the first cycle of chemotherapy. The mean pre-treatment hemoglobin concentration of the patients was 116.67+/-8.17 g/L (mean+/-SD). The mean pre-erythropoietin hemoglobin concentration at baseline was 103.11+/-7.52 g/L. Six cycles of platinum compounds and etoposide were used. The post-treatment hemoglobin concentration of patients was 110.11+/-5.37 g/L (p = 0,028 vs. baseline). During these 54 chemotherapeutic cycles, only 2 patients needed transfusion, each of them once. According to our experience, the use of beta-erythropoietin in 9 anemic small cell lung cancer patients resulted in a low rate of transfusions and maintenance of cytotoxic treatment dose intensity. The adequate use of beta-erythropoietin is of great help to the physician in the management of small cell lung cancer patients.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Small Cell; Cisplatin; Erythropoietin; Etoposide; Female; Hematinics; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Retrospective Studies; Treatment Outcome

Anemia occurs frequently in patients with lung cancer receiving chemotherapy and has a negative impact on quality of life (QoL). Erythropoietic proteins effectively increase hemoglobin (Hb) levels, reduce transfusion requirements and improve QoL in anemic patients with a range of malignancies. This prospective, observational study evaluated epoetin beta 30,000 IU once weekly in patients with lung cancer in a real-life, clinical-practice setting. Forty patients (72.5% with NSCLC and 27.5% with SCLC) were treated with epoetin beta during any cycle of chemotherapy when Hb decreased to <12 g/dL. Hb levels were assessed at regular intervals and transfusion needs were monitored throughout the study. In total, 72.5% of patients required epoetin treatment by the second cycle of chemotherapy. Epoetin beta treatment duration ranged from 1 to >9 (median 4) weeks. Mean (+/-S.D.) baseline Hb was 10.4+/-1.2 g/dL. Epoetin beta was associated with a rapid increase in Hb levels, with a mean increase of 1.3 g/dL by week 4. Most patients (95%) remained transfusion-free throughout the study. Epoetin beta was well tolerated. This early intervention strategy with epoetin beta 30,000 IU once weekly is an effective and well-tolerated therapy for anemia in patients with lung cancer.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Drug Administration Schedule; Erythropoietin; Female; Hemoglobins; Humans; Lung Neoplasms; Male; Middle Aged; Recombinant Proteins

We report two cases of extramedullary erythropoiesis within chronic subdural hematoma that caused diagnostic confusion. In both cases, the initial favored diagnosis by the submitting pathologists was that of a metastatic malignant tumor, including lymphoma, carcinoma, and malignant melanoma. In both cases, the subdural chronic hematoma contained cohesive clusters of small round blue cells with scant cytoplasm and round hyperchromatic nuclei. In both cases, some mitotic figures were identified. There was no gross or microscopic evidence of a meningeal mass lesion. The erythroblastic nature of the cells was confirmed using immunohistochemistry for CD43, glycophorin A, and erythropoietin A. It is important for surgical pathologists to be aware of this benign process and not to overinterpret it as either a primary or metastatic malignant tumor.

Topics: Aged; Antigens, CD34; Brain Neoplasms; Carcinoma, Small Cell; Diagnosis, Differential; Erythropoiesis; Erythropoietin; Female; Gene Expression Regulation, Neoplastic; Glycophorins; Hematoma, Subdural, Chronic; Hematopoiesis, Extramedullary; Humans; Male; Middle Aged

Anemia is very common among patients with malignant tumors, due to the disease and chemotherapy. Anemia decreases the patient's quality of life. Erythropoietin therapy is accessible in Hungary for the treatment of chemotherapy-induced anemia in patients suffering from small cell lung cancer. In our case report we present the case of a 62-year-old female small cell lung cancer patient with severe anemia, treated by erythropoietin-beta. The erythropoietin treatment provided the possibility of effective chemo- and radiotherapy. The patient's quality of life greatly improved due to the lack of the symptoms of anemia. The adequate use of erythropoietin is of great help to the physician in the management of small cell lung cancer patients, by improving the quality of life.

Topics: Anemia, Hypochromic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Small Cell; Chemotherapy, Adjuvant; Erythropoietin; Female; Hematinics; Hematocrit; Hemoglobins; Humans; Lung Neoplasms; Middle Aged; Quality of Life; Radiography; Radiotherapy, Adjuvant; Recombinant Proteins; Treatment Outcome

The goal of this study was to evaluate serum level of EPO in 32 men with lung cancer (Squamous cell lung cancer N = 11, Adenocarcinoma N = 10, Small cell lung cancer N = 11) in relation to the degree of anemia, stage of disease and the regimen of anticancer therapy. The control group consisted of 29 men, among whom were 15 patients with posthemorrhagic anemia. Blood samples were withdrawn for assessment of blood count, serum concentration of EPO, iron, total iron binding capacity (TIBC) and ferritin. The assessment of all parameters was repeated after 3 months of therapy:. Patients suffering from lung cancer were characterized by a lower hemoglobin level and higher level of EPO as compared with the control group. A significant negative correlation was found between hemoglobin level and EPO serum concentration in all groups of patients and in the control group. The strongest correlation was observed in the control group t = -0.812. In each group of patients the serum level of EPO increased after treatment; although a significant increase was found only in surgically treated patients and patients after chemotherapy. After treatment the correlation between hemoglobin and EPO became stronger especially in the group of patients with small cell lung cancer.. 1. Patients with lung cancer are characterized by inappropriately low serum EPO levels when related to the degree of anemia, 2. The suppressive effect of lung cancer on EPO secretion depends on the histological type of the cancer (with the exception of small cell lung cancer). 3. The increase of EPO level after treatment seems to be caused not only by a decrease of hemoglobin concentration, but also by reduction of the tumor mass.

Topics: Adenocarcinoma; Anemia; Biomarkers; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Case-Control Studies; Erythropoietin; Ferritins; Hemoglobin A; Humans; Iron; Lung Neoplasms; Male; Middle Aged; Time Factors

Topotecan is a new antineoplastic agent active in ovarian cancer, with promising activity in small cell lung cancer and predictable toxicity. As a part of our ongoing attempt to optimize the use of disease-specific drugs as circulating progenitor cell (CPC) priming in solid tumors, we have evaluated the effects on CPC release of single-agent Topotecan followed by granulocyte colony-stimulating factor (G-CSF) + human recombinant erythropoietin (rhEPO), together with the cell cycle status of the collected CD34+ cells. Ten pretreated patients with small cell lung cancer received Topotecan (1 mg/m2, i.v. for 5 consecutive days) followed by G-CSF (5 microg/kg/day, s.c.) + rhEPO (10,000 I.U. daily, s.c.), starting 24 h after Topotecan. The combination was well tolerated and no relevant side-effects were recorded. On day +10 (range +9 to +11) after the last dose of Topotecan, the median WBC count and the CD34+ cell peak were 8.2 x 10(3) microl (range 4.9-13.9) and 55 microl (range 28-75), respectively. Using flow cytometry, a detailed cell cycle analysis was performed on these CD34+ cells. The cell cycle distribution was determined by DNA content coupled with bromodeoxyuridine incorporation analysis. Apoptosis was evaluated by quantitating DNA strand breaks. The percentage of CD34+ cells in active S-phase was 10.2+/-5%, while early apoptotic CD34+ cells were detected in a low percentage (5.5+/-3%). Topotecan followed by G-CSF + rhEPO mobilizes CPCs effectively. This sequence exerts a stimulation on CD34+ cell cycle with a protective effect from chemotherapy-induced apoptosis. Taken together, these data could be of value for the incorporation of Topotecan, as well as of the combination of G-CSF and rhEPO, into high-dose chemotherapy programs with CPC support.

Topics: Adult; Aged; Antigens, CD34; Apoptosis; Bromodeoxyuridine; Carcinoma, Small Cell; Cell Cycle; Drug Therapy, Combination; Erythropoietin; Flow Cytometry; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cells; Humans; Leukocyte Count; Lung Neoplasms; Middle Aged; Platelet Count; Recombinant Proteins; Time Factors; Topotecan

The serum erythropoietin level increases markedly during chemotherapy for leukemia. A number of hypotheses have been built for the mechanism, none of them satisfactory. Difficulty in evaluating bone marrow activity hampers the elucidation. Therefore, we focused on patients who had non-hematological cancer and no evidence of bone marrow suppression.. Twelve patients, who had lung cancer (four with small cell cancer and eight with non-small cell cancer) and who had not undergone any chemotherapy, were studied. During chemotherapy, we measured serum erythropoietin, serum iron, unsaturated iron binding capacity and hemoglobin concentration in these patients.. The serum erythropoietin level before chemotherapy (10.8 +/- 7.4 mU/ml) was within the normal range but the peak values after the first treatment (73.4 +/- 90.4 mU/ml) increased in all patients. In the patients with small cell cancer, a transient but marked increase in erythropoietin value (204.6 +/- 167.3 mU/ml) was observed after each session of chemotherapy while hemoglobin concentration decreased gradually. Throughout treatments, elevation of the serum iron concentration and concomitant reduction of unsaturated iron binding capacity were observed after each session of chemotherapy. They regained their original values whilst the serum erythropoietin level decreased after each chemotherapy session was completed.. It is suggested that the suppression of erythroid marrow by chemotherapeutic agents causes the changes in serum erythropoietin level during chemotherapy in patients with lung cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Erythropoietin; Female; Hemoglobins; Humans; Iron; Lung Neoplasms; Male; Middle Aged; Protein Binding

Many studies have been done in order to elucidate the pathogenesis of the anaemia of chronic disorders accompanying cancer, with conflicting results. This is probably due to the heterogeneity of the patient population selected for these studies (many patients treated by chemotherapy). To avoid this pitfall, in this study a very homogenous group of chemotherapy and radiotherapy-naive patients with lung cancer were selected. Serum erythropoietin and soluble transferrin receptor measurements suggested that the anaemia of non-treated lung cancer is mainly due to an impaired erythroid marrow response to erythropoietin stimulation. However, a relative inadequacy of erythropoietin production may also contribute.

Topics: Anemia; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Erythropoiesis; Erythropoietin; Female; Humans; Lung Neoplasms; Male; Receptors, Transferrin

We examined the efficacy of low-dose erythropoietin in the management of chemotherapy-related anaemia in patients with small cell lung cancer (SCLC). We gave recombinant human erythropoietin A (rHuEPO) to 63 SCLC patients, 30 with limited disease (LD) and 33 with extensive disease (ED) who underwent chemotherapy with carboplatin, etoposide and ifosfamide and had previously received blood transfusions for chemotherapy-related anaemia. rHuEPO was given at a dose of 2000 IU subcutaneously three times per week for 2 weeks after every chemotherapy cycle, starting 48 h after the end of chemotherapy. Before the use of rHuEPO, all patients in both groups had to be transfused after a mean of 5.5 CT cycles. In 64 CT cycles following administration of rHuEPO, only 5/30 LD patients (17%) had to be transfused in six cycles (9%). In 88 cycles following the use of rHuEPO, 7/33 ED patients (21%) had to be transfused in 11 cycles (12.5%). Haemoglobin values in patients with ED (but not those with LD) were significantly improved after rHuEPO administration on both day 14 and day 28 after chemotherapy. No adverse effects were recorded. rHuEPO considerably decreased the degree of anaemia and the need for blood transfusion at doses markedly lower (25-30 IU/kg body weight) than those reported in the literature so far (150 IU/kg body weight), without toxicity.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Small Cell; Erythropoietin; Etoposide; Humans; Ifosfamide; Lung Neoplasms; Male; Middle Aged; Recombinant Proteins; Retrospective Studies

Topics: alpha-Fetoproteins; Carcinoma, Small Cell; Erythropoietin; Humans; Lung Neoplasms; Male; Middle Aged; Polycythemia

The relationships between prognostic factors and duration of survival in small cell lung cancer were investigated in a consecutive series of 874 patients treated with combination chemotherapy with or without irradiation. The series included 443 patients with limited and 431 patients with extensive stage disease based on staging including bone marrow examination and peritoneoscopy with liver biopsy but no routine scans. The median durations of survival for the two disease categories were 48 and 30 weeks, respectively. The influence on survival of various pretreatment factors was investigated by use of univariate methods and Cox's multivariate regression model. Patients in each stage were treated according to one of three controlled trials. Variations among the applied treatment regimens did not result in significant differences in duration of survival among patients with limited disease. An alternating regimen was superior to continuous therapy in patients with extensive disease and raised serum lactate dehydrogenase. Prognosis was correlated with disease extent. Surgical resection as well as limited stage disease thus both contributed to survival. Poor performance status, reduced hemoglobin concentration, and raised values for serum lactate dehydrogenase were significantly associated with a reduced duration of survival in both stages. Females with limited disease lived significantly longer than males while advanced age was a negative prognostic factor in extensive disease. Plasma sodium and serum urate were both predictive of survival in limited disease. Proved metastatic disease affecting specific sites or total number of metastatic sites did not carry significant prognostic information in a model including a general variable characterizing stage of disease. Fifty of the 778 patients, on whom the multiple regression model was based, were alive and disease free 2 years after the start of the treatment. Two-year survival rates were strongly correlated to groupings based on prognostic factors, and information about disease extent was not mandatory for predicting the probability of long term disease-free survival.

Topics: Adult; Aged; Alkaline Phosphatase; Carcinoma, Small Cell; Combined Modality Therapy; Erythropoietin; Female; Hormones, Ectopic; Humans; L-Lactate Dehydrogenase; Lung Neoplasms; Male; Middle Aged; Models, Biological; Neoplasm Metastasis; Prognosis; Regression Analysis; Risk; Vasopressins

Among the malignant tumors of nonendocrine origin that are capable of producing polypeptide hormones and of manifesting as different endocrine syndromes discussed here are ectopic ACTH syndrome, SIADH, and ectopic gonadotropin-producing tumors.

Topics: Adrenocorticotropic Hormone; Carcinoma, Hepatocellular; Carcinoma, Small Cell; Chorionic Gonadotropin; Cushing Syndrome; Diagnosis, Differential; Erythropoietin; Follicle Stimulating Hormone; Gynecomastia; Hormones, Ectopic; Humans; Hyperthyroidism; Hypoglycemia; Hyponatremia; Liver Neoplasms; Lung Neoplasms; Luteinizing Hormone; Male; Paraneoplastic Endocrine Syndromes; Polycythemia; Puberty, Precocious; Thyrotropin; Vasopressins; Water Intoxication