epoetin-alfa and Breast-Neoplasms

The treatment of cancer-induced anemia with erythropoietin-stimulating agents (ESAs) is reviewed.. Before the introduction of ESAs, the only treatment option for cancer-related anemia was red blood cell (RBC) transfusion. The use of ESAs in multiple disease states has been well established and is now considered first-line treatment for many forms of anemia. Chang et al. evaluated the effect of epoetin alfa (40,000 units administered subcutaneously every week) and standard-of-care therapy on quality of life (QOL), transfusion requirements, and hemoglobin levels in 354 patients with breast cancer who had a baseline hemoglobin concentration of <15 g/dL. The authors concluded that early initiation of treatment with epoetin alfa in patients with breast cancer is effective in maintaining hemoglobin levels, reducing transfusions, and improving QOL. Leyland-Jones et al. conducted a study evaluating the effects of early intervention with epoetin alfa (40,000 units administered subcutaneously every week) on survival and QOL of mainly nonanemic patients with metastatic breast cancer. In contrast to Chang et al., this study was discontinued because of lower overall survival rates within the epoetin alfa group. In 2008, the Food and Drug Administration issued a black-box warning for both epoetin alfa and darbepoetin alfa. The warning acknowledges that ESAs have shortened overall survival and time to disease progression in patients with advanced breast cancer who are given these agents to achieve a target hemoglobin concentration of > or =12 g/dL.. When used in patients with cancer-induced anemia, ESAs should only be given at the lowest dose possible to prevent RBC transfusions. During treatment, hemoglobin levels should be monitored closely and ESA doses need to be adjusted accordingly.

Topics: Anemia; Blood Transfusion; Breast Neoplasms; Darbepoetin alfa; Drug Labeling; Drug Monitoring; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Survival Rate

Many patients with breast cancer suffer from anaemia, as a consequence of the disease itself or its treatment. Anaemia has a negative impact on treatment outcome and overall survival, and affects the quality of life (QoL) of patients with cancer. Previously, cancer-related anaemia was treated with blood transfusion, but this is inconvenient, offers only temporary improvement in haemoglobin (Hb) level and is associated with several risks. Consequently, blood transfusion is usually reserved for patients with severe anaemia (Hb levels <8 g/dl). Recombinant human erythropoietin (epoetin) is an effective and convenient treatment for cancer-related anaemia without the risks associated with red blood cell transfusion. Epoetin therapy effectively increases Hb levels, thereby reducing the need for emergency blood transfusion and improving the QoL of patients with anaemia and breast cancer. Epoetin beta is also effective for the prevention of anaemia and reduction of transfusion requirements in patients with a high risk of developing anaemia during chemotherapy. With the increased use of dose-intensified chemotherapy in an attempt to improve response rates, administration of epoetin to prevent anaemia could potentially benefit many patients with breast cancer.

Topics: Adult; Age Distribution; Aged; Anemia, Hypochromic; Breast Neoplasms; Combined Modality Therapy; Comorbidity; Dose-Response Relationship, Drug; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Humans; Incidence; Middle Aged; Neoplasm Staging; Prognosis; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins; Risk Assessment; Severity of Illness Index; Sex Distribution; Survival Rate; Treatment Outcome

Treatment with recombinant human erythropoietin (epoetin alfa) has been shown to enhance quality of life and cognitive function. The mechanism of action for these changes appears to involve more than the alleviation of cancer treatment-induced anemia. Rather, there is increasing evidence that epoetin alfa treatment may modulate a series of cascading events that involve hypoxia-induced activation of vascular endothelial growth factor and an induction in the expression of vascular endothelial growth factor receptors via a hypoxia-inducible factor-1-mediated transcription among several other hypoxia-related events. The use of epoetin alfa to interfere with this hypoxia-induced cascade could provide significant benefits for cancer patients by enhancing survival through a direct modulation of tumor angiogenesis and effectiveness of cancer therapy. The enhanced quality of life seen with erythropoietin treatment may also involve a modulation of hypoxia-induced decrement in cognitive functioning. It appears that epoetin alfa is a useful addition to the treatment of breast cancer.

Topics: Angiogenesis Inhibitors; Apoptosis; Breast Neoplasms; Cell Hypoxia; Central Nervous System; Cognition; Epoetin Alfa; Erythropoietin; Hematinics; Humans; Neoplasms; Neovascularization, Pathologic; Recombinant Proteins

Chemotherapy-associated cognitive dysfunction occurs in a subset of patients treated with adjuvant chemotherapy. Recent data suggest that development of chemotherapy-related anemia predisposes patients to cognitive dysfunction. Endogenous erythropoietin (EPO) is well recognized for its central role in erythropoiesis, and recombinant human EPO (epoetin alfa) is established as a safe and effective treatment for chemotherapy-related anemia. Treatment with epoetin alfa also improved health-related quality of life in anemic cancer patients undergoing chemotherapy, and several controlled studies have documented increases in quality-of-life scores correlated with increases in hemoglobin. Erythropoietin also plays a role in neuroprotection, presumably by activation of antiapoptotic genes. Erythropoietin and its receptor are expressed in neural cells of the human brain, and their expression is upregulated after hypoxic or ischemic injury. In animal models, systemic administration of epoetin alfa protects against such neural injury. Ongoing and future studies will determine whether epoetin alfa can provide neuroprotection with respect to the development of cognitive dysfunction in patients undergoing adjuvant chemotherapy treatment for breast cancer.

Topics: Anemia; Animals; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cognition Disorders; Disease Models, Animal; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Quality of Life; Rats; Recombinant Proteins

Several recently published studies describe moderate to severe cognitive dysfunction in breast cancer survivors who were treated with adjuvant chemotherapy 1-5 years before undergoing extensive neuropsychological testing. While these studies are hypothesis-generating and preliminary given their small size and retrospective nature, they consistently suggest that between approximately 15% and 25% of chemotherapy-treated breast cancer patients will have evidence of cognitive dysfunction some years after chemotherapy, compared to about 10% of breast cancer survivors who did not receive chemotherapy. Recent preclinical data strongly suggest that erythropoetin is a potent, endogenous neuroprotective agent that prevents neuronal apoptosis from a variety of insults including hypoxia, trauma, subarachnoidal hemorrhage, and encephalitis. Erythropoietin also appears to enhance learning in a mouse spatial learning maze model. We have conducted a pilot study of epoetin alfa versus placebo in early-stage breast cancer patients who received standard adjuvant anthracycline-based chemotherapy to determine the feasibility of administering standardized neurocognitive assessment tests in the oncology practice setting in order to understand whether the Executive Interview 25 test can detect the subtle cognitive impairment in verbal fluency, attention, and short-term memory observed with chemotherapy, and to assess whether epoetin alfa-treated patients have less evidence of cognitive dysfunction during and 6 months after chemotherapy compared with control-treated patients. We report here the preliminary results of this pilot clinical trial.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Asthenia; Breast Neoplasms; Chemotherapy, Adjuvant; Cognition Disorders; Controlled Clinical Trials as Topic; Disease Models, Animal; Epoetin Alfa; Erythropoietin; Female; Humans; Mastectomy; Mice; Mood Disorders; Patient Satisfaction; Pilot Projects; Prognosis; Quality of Life; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

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

Breast cancer patients undergoing therapeutic regimens of high-dose chemotherapy (HDCT) with circulating progenitor cell support often develop anemia. As a general consideration in the transplantation setting, red blood cell transfusions are normally required in patients who have passed the myeloablative phase after HDCT. In the initial 30-day period immediately following HDCT, the number of red blood cell units that are transfused will usually depend on a number of factors, including whether the transplantation was allogeneic or autologous. Observations and results from clinical studies have shown that the establishment of normal erythropoiesis varies depending on the source of the transplanted cells, resulting in different transfusion requirements. Several studies support the use of recombinant human erythropoietin (rHuEPO, epoetin alfa) after HDCT to ameliorate anemia and reduce transfusion requirements. Studies have also shown that administration of epoetin alfa prior to the myeloablative phase is an effective method for reducing red blood cell transfusion requirements in breast cancer patients receiving HDCT. Epoetin alfa in combination with other cytokines has been shown to positively affect the mobilization phase of hematopoietic progenitor cells for autografting. Furthermore, treatment with epoetin alfa could prove useful in bone marrow transplant recipients who experience delayed anemia. Recent studies that have addressed these topics in breast cancer indicate that, when used in the appropriate setting, epoetin alfa may play a role as a tool to decrease the need for red blood cell transfusion in patients undergoing HDCT plus autologous circulating progenitor cell support.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Bone Marrow Transplantation; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Hematinics; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Recombinant Proteins

Anemia is a common complication of myelosuppressive chemotherapy that results in a decreased functional capacity and quality of life (QOL) for cancer patients. Severe anemia is treated with red blood cell transfusions, but mild-to-moderate anemia in patients receiving chemotherapy has traditionally been managed conservatively on the basis of the perception that it was clinically unimportant. This practice has been reflected in the relative inattention to standardized and complete reporting of all degrees of chemotherapy-induced anemia. We undertook a comprehensive review of published chemotherapy trials of the most common single agents and combination chemotherapy regimens, including the new generation of chemotherapeutic agents, used in the treatment of the major nonmyeloid malignancies in adults to characterize and to document the incidence and severity of chemotherapy-induced anemia. Despite identified limitations in the grading and reporting of treatment-related anemia, the results confirm a relatively high incidence of mild-to-moderate anemia. Recent advances in assessing the relationships of anemia, fatigue, and QOL in cancer patients are providing new insights into these closely related factors. Clinical data are emerging that suggest that mild-to-moderate chemotherapy-induced anemia results in a perceptible reduction in a patient's energy level and QOL. Future research may lead to new classifications of chemotherapy-induced anemia that can guide therapeutic interventions on the basis of outcomes and hemoglobin levels. Perceptions by oncologists and patients that lesser degrees of anemia must be endured without treatment may be overcome as greater emphasis is placed on the QOL of the oncology patient and as research provides further insights into the relationships between hemoglobin levels, patient well-being, and symptoms.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Clinical Trials as Topic; Colorectal Neoplasms; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Female; Head and Neck Neoplasms; Hematinics; Humans; Incidence; Lung Neoplasms; Lymphoma; Middle Aged; Neoplasms; Ovarian Neoplasms; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

Hematologic toxicities are one of the greatest challenges in adjuvant chemotherapy for breast cancer. This analysis of the ADEBAR trial aims to evaluate application and effect of granulocyte colony-stimulating factor (G-CSF) and epoetin alfa (EPO) on hematologic parameters and fatigue in patients with breast cancer during chemotherapy.. In the ADEBAR trial, 1493 patients with node-positive primary breast cancer were randomized to either 6 × 5-fluorouracil, epirubicin, and cyclophosphamide (FEC120) or 4 × epirubicin and cyclophosphamide followed by 4 × docetaxel (EC-DOC). Co-medication with G-CSF or EPO was applied to treat chemotherapy-induced leukopenia or anemia. Fatigue was assessed at baseline and after one-half of the chemotherapy.. In total, 899 patients could be included in the analysis. There was no evidence for an association between leucocyte or hemoglobin levels and application of G-CSF and EPO in the preceding cycle, respectively. Hemoglobin levels (B = -0.41; P < .001) were affected by treatment regimen. Fatigue during chemotherapy was mostly affected by the level of fatigue before the start of chemotherapy (B = 0.41; P < .001). Patients with G-CSF application in the preceding cycle showed an increased fatigue score (B = 5.43; P = .02).. We showed that fatigue during adjuvant chemotherapy was mostly affected by the level of fatigue present before the start of chemotherapy. This result suggests that the level of fatigue before the start of treatment should be included as an important factor when deciding on type and toxicity of chemotherapy in early breast cancer.

Topics: Adolescent; Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Epoetin Alfa; Fatigue; Female; Granulocyte Colony-Stimulating Factor; Hemoglobins; Humans; Leukocyte Count; Leukopenia; Middle Aged; Neoplasm Staging; Prospective Studies; Quality of Life; Severity of Illness Index; Young Adult

An open-label, noninferiority study to evaluate the impact of epoetin alfa (EPO) on tumor outcomes when used to treat anemia in patients receiving chemotherapy for metastatic breast cancer.. Women with hemoglobin ≤ 11.0 g/dL, receiving first- or second-line chemotherapy for metastatic breast cancer, were randomly assigned to EPO 40,000 IU subcutaneously once a week or best standard of care. The primary end point was progression-free survival (PFS). Secondary end points included overall survival, time to tumor progression, overall response rate, RBC transfusions, and thrombotic vascular events.. In 2,098 patients randomly assigned, median PFS (based on investigator-determined disease progression [PD]) was 7.4 months in both groups (hazard ratio [HR], 1.089; 95% CI, 0.988 to 1.200); upper bound exceeded prespecified noninferiority margin of 1.15. Median PFS per independent review committee-determined PD was 7.6 months in both groups (HR, 1.028; 95% CI, 0.922 to 1.146); upper bound did not exceed prespecified noninferiority margin. Median overall survival at clinical cutoff (1,337 deaths) was 17.2 months in the EPO and 17.4 months in the best standard of care group (HR, 1.057; 95% CI, 0.949 to 1.177), median time to tumor progression was 7.5 months in both groups (HR, 1.094; 95% CI, 0.991 to 1.209), and overall response rate was 50% versus 51% (odds ratio, 0.950; 95% CI, 0.799 to 1.130). RBC transfusions were 5.8% versus 11.4% (P < .001), and thrombotic vascular events were 2.8% versus 1.4% (P = .038), respectively.. The primary end point, PFS based on investigator-determined PD, did not meet noninferiority criteria. As a consistency assessment with the primary finding, PFS based on independent review committee-determined PD met noninferiority criteria. Overall, this study did not achieve noninferiority objective in ruling out a 15% increased risk in PD/death. RBC transfusion should be the preferred approach for the management of anemia in this population.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Disease Progression; Drug Administration Schedule; Epoetin Alfa; Female; Hematinics; Humans; Kaplan-Meier Estimate; Middle Aged; Odds Ratio; Quality of Life; Standard of Care; Treatment Outcome

The AGO-ETC trial compared 5-year relapse-free survival of intense dose-dense (IDD) sequential chemotherapy with epirubicin (E), paclitaxel (T), and cyclophosphamide (C) (IDD-ETC) every 2 weeks vs conventional scheduled epirubicin/cyclophosphamide followed by paclitaxel (EC→T) (every 3 weeks) as adjuvant treatment in high-risk breast cancer patients. The objective of this study was to evaluate the safety and efficacy of epoetin alfa in a second randomization of the intense dose-dense arm.. One thousand two hundred eighty-four patients were enrolled; 658 patients were randomly assigned to the IDD-ETC treatment group. Within the IDD-ETC group, 324 patients were further randomly assigned to the epoetin alfa group, and 319 were randomly assigned to the non-erythropoiesis-stimulating agent (ESA) control group. Primary efficacy endpoints included change in hemoglobin level from baseline to Cycle 9 and the percentage of subjects requiring red blood cell transfusion. Relapse-free survival, overall survival, and intramammary relapse were secondary endpoints estimated with Kaplan-Meier and Cox regression methods. Except for the primary hypothesis, all statistical tests were two-sided.. Epoetin alfa avoided the decrease in hemoglobin level (no decrease in the epoetin alfa group vs -2.20g/dL change for the control group; P < .001) and statistically significantly reduced the percentage of subjects requiring red blood cell transfusion (12.8% vs 28.1%; P < .0001). The incidence of thrombotic events was 7% in the epoetin alfa arm vs 3% in the control arm. After a median follow-up of 62 months, epoetin alfa treatment did not affect overall survival, relapse-free survival, or intramammary relapse.. Epoetin alfa resulted in improved hemoglobin levels and decreased transfusions without an impact on relapse-free or overall survival. However, epoetin alfa had an adverse effect, resulting in increased thrombosis.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Blood Transfusion; Breast Neoplasms; Chemotherapy, Adjuvant; Cyclophosphamide; Disease-Free Survival; Drug Administration Schedule; Epirubicin; Epoetin Alfa; Erythropoietin; Female; Follow-Up Studies; Hematinics; Hemoglobins; Humans; Kaplan-Meier Estimate; Middle Aged; Paclitaxel; Proportional Hazards Models; Quality of Life; Recombinant Proteins; Risk Assessment; Treatment Outcome

To evaluate the effects of epoetin alfa on patient-reported outcomes (PROs) in patients with breast cancer receiving myelotoxic chemotherapy.. Women with hemoglobin concentrations ≤ 12.0 g/dl and an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-3 were randomized 1:1 to receive epoetin alfa (10,000 IU 3 times weekly) or best standard care (BSC) during chemotherapy. The primary endpoint was the change from baseline in the total anemia subscale assessed by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) questionnaire after 12 weeks of treatment. The fatigue and nonfatigue subscales from the FACT-An, the Cancer Linear Analog Scale (CLAS), hemoglobin changes, ECOG PS score, tumor response, overall survival, and safety also were evaluated.. Of 223 patients randomized, 216 constituted the modified intent-to-treat population. Percentage changes in the total anemia subscale of the FACT-An were significantly different between epoetin alfa treatment (14.2%) and BSC (-0.5%; p = .002), favoring epoetin alfa; so were changes in the FACT-An fatigue subscale (epoetin alfa, 17.5%; BSC, -0.9%; p = .003) and nonfatigue subscale (epoetin alfa, 8.8%; BSC, 0.2%; p = .008). Similar results were observed with the CLAS. Hemoglobin concentrations > 12 g/dl were more common with epoetin alfa (62.0%) than with BSC (27.6%). Tumor response, ECOG PS score, 12-month survival rate, and the incidence of serious treatment-emergent adverse events were similar between groups.. Early intervention with epoetin alfa was well tolerated and improved anemia-related PROs in patients with breast cancer receiving myelotoxic chemotherapy.

Topics: Adult; Aged; Anemia; Antineoplastic Agents; Blood Transfusion; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Middle Aged; Prospective Studies; Recombinant Proteins

This prospective study quantifies the response of hemoglobin and other blood factors to Epoetin alpha (EPO) administration in the course of pre-operative chemotherapy in breast cancer. Blood count time series were analyzed in 38 primary breast cancer patients with/without EPO during the course of pre-operative chemotherapy with epirubicin and paclitaxel. EPO injections improved blood counts in 'anemic' patients (< or =12.0 g/dl) receiving chemotherapy, but had little effect when administered to patients with higher hemoglobin concentrations. On the average, without chemotherapy, hemoglobin concentrations drifted toward about 11.1 g/dl without EPO but could be maintained at near 12.0 g/dl with EPO. In conclusion, there is potential for improved anemia management using EPO during pre-operative chemotherapy, which not only benefits quality of life but could also influence long-term survival in breast cancer through improved tumor oxygenation.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Combined Modality Therapy; Epirubicin; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Middle Aged; Neoadjuvant Therapy; Paclitaxel; Recombinant Proteins

To determine whether weekly epoetin alfa could improve hemoglobin (HgB) levels, reduce RBC transfusions, and improve quality of life (QOL) in patients with advanced cancer and with anemia after receiving myelosuppressive chemotherapy.. This double-blind, placebo-controlled study randomly assigned patients to placebo or epoetin alfa (Ortho Biotech, Bridgewater, NJ) 40,000 U subcutaneous weekly for 16 weeks. QOL, HgB, and RBC transfusions were measured pretreatment and monthly.. The study accrued 344 patients; 330 were assessable for efficacy and 305 were assessable for QOL. Placebo-treated patients had a mean increase in HgB of 0.9 g/dL (range, -3.8 to +5.3) compared with 2.8 g/dL (range, -2.2 to +7.5) for epoetin-treated patients (P < .0001). During the study, 31.7% of placebo-treated patients achieved a > or = 2 g/dL HgB increase compared with 72.7% of epoetin-treated patients (P < .0001). The incidence of RBC transfusion for placebo and epoetin treatment arms was 39.6% and 25.3% (P = .005), respectively. The placebo group received 256 units of RBCs compared with 127 units in the epoetin group (P < .0001). The incidence of toxicity in the groups was similar. Changes in the average QOL scores from baseline to the end of the study were similar in the two groups (P = not significant). The HgB responders (irrespective of treatment arm) had a mean change in Functional Assessment of Cancer Therapy (FACT) fatigue score from a baseline of +5.1 compared with -2.1 for the nonresponders (P = .006).. Epoetin alfa significantly improved HgB and reduced transfusions in this patient population. These results support the use of weekly epoetin alfa as an ameliorative agent for cancer-related anemia.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Breast Neoplasms; Double-Blind Method; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Hemoglobins; Humans; Injections, Subcutaneous; Lung Neoplasms; Male; Middle Aged; Neoplasms; Placebos; Quality of Life; Recombinant Proteins; Treatment Outcome

Epoetin alfa administered at 40,000 U once weekly (qw) to anemic cancer patients receiving chemotherapy increases hemoglobin levels, improves quality of life (QOL), and reduces transfusions. The benefit of epoetin alfa in maintaining hemoglobin levels in cancer patients with hemoglobin less than 12 g/dL has not been evaluated.. Breast cancer patients (N = 354) receiving chemotherapy were randomly assigned in 1:1 ratio to epoetin alfa (40,000 U qw) or standard of care (SOC). QOL was assessed at baseline and week 12. Hemoglobin responses, transfusion requirements, and prognostic factors for responses were measured.. At week 12, Functional Assessment of Cancer Therapy-Anemia (FACT-An; mean, 2.16 +/- 12.84 for epoetin alfa v -4.43 +/- 13.42 for SOC) and FACT-An fatigue (mean, 1.85 +/- 10.52 for epoetin alfa v -3.55 +/- 11.14 for SOC) change scores were significantly higher in the epoetin alfa group (P < .0001). Hemoglobin responses defined as mean hemoglobin > or = 12 g/dL or a > or = 2 g/dL increase compared with baseline were significantly higher in the epoetin alfa group versus SOC: 52.0% v 5.1% and 65.7% v 6.3%, respectively (P < .0001 for both comparisons). Percentage transfused was significantly lower in the epoetin alfa group compared with SOC (8.6% v 22.9%). More than 90% of patients did not require a dose increase and 28.7% had a dose reduction.. Epoetin alfa administered at 40,000 U qw is effective in improving QOL, maintaining hemoglobin level, and reducing transfusion requirements in breast cancer patients. The high effectiveness observed could be attributed in part to early treatment with epoetin alfa.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Middle Aged; Quality of Life; Recombinant Proteins; Treatment Outcome

Impaired cognition, fatigue, and diminished quality of life (QOL) are commonly associated with breast cancer chemotherapy. This randomized, double-blind, placebo-controlled pilot trial assessed the feasibility of quantifying the effects of epoetin alfa on cognitive function and mood, and evaluated its effects on fatigue and QOL in patients with breast cancer treated with anthracycline-based adjuvant or neoadjuvant chemotherapy. Patients were randomized to receive epoetin alfa 40,000 U subcutaneously once weekly or placebo at the beginning of 4 cycles of chemotherapy administered over 12 weeks. Cognitive function was assessed by Executive Interview (EXIT25) and Clock Drawing Tasks; mood by Profile of Mood States; anemia-related symptoms, including fatigue, by the Functional Assessment of Cancer Therapy-Anemia (FACT-An) subscale; and QOL by Linear Analog Scale Assessment. Ninety-four patients were evaluable for efficacy and safety. Mean change in EXIT25 scores from baseline to cycle 4 in the epoetin alfa group was 1.3 +/- 3.3; the mean change was 0.3 +/- 2.4 in the placebo group (a negative change indicates improved executive function). There was no difference between groups in mean change in EXIT25 score from baseline to 6-month follow-up assessment. Mean hemoglobin levels were higher in the epoetin alfa group compared with the placebo group after 4 cycles of chemotherapy. Epoetin alfa recipients had less of a decrease in FACT-An subscale scores from baseline to cycle 4 and improvement in FACT-An subscale scores at 6-month follow-up assessment compared with placebo. Epoetin alfa therapy was well tolerated. These data suggest that epoetin alfa may have attenuated the cognitive impairment and fatigue that occurred during adjuvant breast cancer chemotherapy.

Topics: Adult; Affect; Aged; Breast Neoplasms; Chemotherapy, Adjuvant; Cognition Disorders; Double-Blind Method; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Humans; Injections, Subcutaneous; Middle Aged; Neoadjuvant Therapy; Placebos; Quality of Life; Recombinant Proteins; Treatment Outcome

Anemia, fatigue, and diminished quality of life (QOL) often are associated with chemotherapy. In a previous study of patients with early-stage breast cancer and a mean baseline hemoglobin (Hb) level of 12.1 g/dL, Hb decreased by 2.0 g/dL after 4 cycles of adjuvant chemotherapy. The current open-label, nonrandomized, multicenter, prospective, community-based study evaluated the effects of 12-24 weeks of epoetin alfa (40,000 U subcutaneously once weekly initiated at the start of standard adjuvant chemotherapy) in patients with stage I-III breast cancer and baseline Hb levels > or =10 g/dL to < or =14 g/dL on Hb level, transfusions, and QOL.. Of 1792 patients enrolled, 1785 were evaluable for safety and 1632 for efficacy. Mean age was 53 years +/- 10.7 and mean baseline Hb level was 12.3 g/dL +/- 1.0. From baseline levels, epoetin alfa significantly increased Hb (1.3 g/dL +/- 1.5; P < 0.05) and improved QOL according to the Linear Analog Scale Assessment (LASA) of energy (5.1 mm +/- 27.7), LASA activity (5.1 mm +/- 28.2), LASA overall QOL (4.3 mm +/- 26.7), and Functional Assessment of Cancer Therapy-Anemia (1.7 points +/- 14.0; P < 0.05 in each case). Patients with baseline mild anemia (Hb level >10 g/dL to < or =12 g/dL) also had significant improvements from baseline levels in all 3 LASA parameters (P < 0.05). Epoetin alfa was well tolerated; clinically relevant thrombovascular events were reported in 4.3% of patients.. In this study, epoetin alfa significantly improved Hb and QOL in mildly anemic patients with early-stage breast cancer receiving adjuvant chemotherapy. However, based on recent studies showing an increased risk of thrombovascular events in patients with cancer treated with erythropoietic agents beyond correction of anemia, treatment with epoetin alfa is not indicated or recommended in patients with cancer and Hb levels > 12 g/dL.. Controlled studies are warranted to confirm the safety and efficacy of epoetin alfa therapy in patients with mild anemia receiving chemotherapy.

Topics: Adult; Anemia; Breast Neoplasms; Chemotherapy, Adjuvant; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Middle Aged; Prospective Studies; Quality of Life; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

To evaluate the effect on survival and quality of life of maintaining hemoglobin (Hb) in the range of 12 to 14 g/dL with epoetin alfa versus placebo in women with metastatic breast cancer (MBC) receiving first-line chemotherapy.. Eligible patients were randomly assigned to receive epoetin alfa 40,000 U once weekly or placebo for 12 months. Study drug was initiated if baseline Hb was < or = 13 g/dL or when Hb decreased to < or = 13g/dL during the study. The primary end point was 12-month overall survival (OS).. The study drug administration was stopped early in accordance with a recommendation from the Independent Data Monitoring Committee because of higher mortality in the group treated with epoetin alfa. Enrollment had been completed, with 939 patients enrolled (epoetin alfa, n = 469; placebo, n = 470). Most patients had Hb more than 12 g/dL at baseline (median Hb, 12.8 g/dL) or during the study. From the final analysis, 12-month OS was 70% for epoetin alfa recipients and 76% for placebo recipients (P = .01). Optimal tumor response and time to disease progression were similar between groups. The reason for the difference in mortality between groups could not be determined from additional subsequent analyses involving both study data and chart review.. In this trial, the use of epoetin alfa to maintain high Hb targets in women with MBC, most of whom did not have anemia at the start of treatment, was associated with decreased survival. Additional research is required to clarify the potential impact of erythropoietic agents on survival when the Hb target range is 10 to 12 g/dL.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Injections, Subcutaneous; Middle Aged; Neoplasm Metastasis; Placebos; Quality of Life; Recombinant Proteins; Survival Analysis

At present, oncologists prescribe chemotherapy according to standard dose schedules, and as a result many patients develop serious, dose-limiting toxic effects such as anaemia. We aimed to develop a prediction model for anaemia in patients with breast cancer who were receiving adjuvant chemotherapy.. We reviewed medical records of 331 patients who had received adjuvant chemotherapy for breast cancer. Patients were divided randomly into a derivation sample (n=221) and internal-validation sample (n=110). An external sample of 119 patients enrolled onto the control group of a randomised trial of epoetin alfa was used to validate the model further. Multivariable logistic regression was applied to develop the initial model. We then developed a risk-scoring system, ranging from 0 (low risk) to 50 (high risk), based on the final regression variables. A receiver operating characteristic (ROC) curve analysis was done to measure the accuracy of the scoring system when applied to both validation samples.. The risk of anaemia increased as the pretreatment haemoglobin concentration decreased and was reduced with successive chemotherapy cycles. Risk was also predicted by a platelet count of 200x10(9) cells/L or less before chemotherapy, age 65 years or older, type of adjuvant chemotherapy, and use of prophylactic antibiotics. ROC analysis had acceptable areas under the curve of 0.88 for the internal-validation sample and 0.84 for the external validation sample. A risk score of > or = 24 to < 25 before chemotherapy was identified as the optimum cut-off for maximum sensitivity (83.5%) and specificity (92.3%) of the prediction model.. The application and continued refinement of this prediction model will help oncologists to identify patients at risk of developing anaemia during chemotherapy for breast cancer, and might enhance patient-centred care by the application of anaemia treatment in a proactive and appropriate way.

Topics: Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Chemotherapy, Adjuvant; Epoetin Alfa; Erythropoietin; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematinics; Humans; Logistic Models; Medical Records; Middle Aged; Predictive Value of Tests; Recombinant Proteins; Risk Factors; ROC Curve

Current chemotherapy regimens for breast cancer result in high incidences of anemia, which can be treated with erythropoietic agents. The relative efficacy of darbepoetin alfa and epoetin alfa was explored in this phase II, open-label, randomized, multicenter trial in anemic patients with breast cancer receiving chemotherapy.. Patients were randomized at a 1:1 ratio to receive darbepoetin alfa 200 microg every 2 weeks (n = 72) or epoetin alfa 40,000 U weekly (n = 69) for < or = 16 weeks. Clinical and hematologic endpoints and validation of a novel patient satisfaction questionnaire for anemia treatment were evaluated for all patients randomized to receive > or = 1 dose of study drug.. Baseline characteristics were generally similar between treatment groups. Mean changes in hemoglobin (Hb) level from baseline were similar at 1.9 g/dL for darbepoetin alfa and 1.7 g/dL for epoetin alfa. Hematopoietic responses (> or = 2 g/dL increase in Hb level from baseline or Hb level > or = 12 g/dL) were also similar between groups (88% for darbepoetin alfa and 81% for epoetin alfa). The proportions of patients who received a transfusion during treatment were 6% (95% CI, 0-11%) for darbepoetin alfa and 16% (95% CI, 7%-25%) for epoetin alfa. Most patients (67 patients receiving darbepoetin alfa [93%]; 61 patients receiving epoetin alfa [90%]) exhibited a clinically meaningful target Hb level > or = 11 g/dL. No differences in safety were observed.. These results suggest that, in patients with breast cancer, darbepoetin alfa 200 microg every 2 weeks and epoetin alfa 40,000 U weekly result in comparable clinical outcomes for the treatment of chemotherapy-induced anemia.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Darbepoetin alfa; Drug Administration Schedule; Epoetin Alfa; Erythropoietin; Female; Humans; Middle Aged; Patient Satisfaction; Recombinant Proteins; 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

In a multinational trial of anaemic patients with cancer receiving nonplatinum-containing chemotherapy, epoetin-alfa effectively increased haemoglobin levels, reduced red blood cell transfusion requirements, and improved QOL. Although the study was not designed or powered to evaluate survival, a survival trend was noted favouring epoetin-alfa compared with placebo (median survival 17 vs 11 months [p = 0.126]).. To determine the incremental cost utility of epoetin-alfa versus placebo in anaemic patients with stage IV breast cancer from a UK National Health Service perspective.. Patient data regarding transfusions, epoetin-alfa usage, chemotherapy treatment cycles, and adverse events were recorded, with survival follow-up for 12-36 months post-study. Stage IV breast cancer therapy costs were collected by surveying UK oncologists, and utilities for associated health states were from published sources. Costs were in British pounds and year 2000 values. Costs and benefits were jointly determined for the stage IV breast cancer subgroup (n = 55). Incremental cost-utility ratios (ICURs) were calculated assuming a 6% annual discount rate for costs and a 1.5% annual discount rate for benefits. Bootstrap simulations (10,000 iterations) were conducted to account for uncertainty, and sensitivity analyses were conducted to establish robustness.. The ICUR for epoetin-alfa treatment was pounds 8,851 per QALY, with a 99% probability of a positive net benefit in QALYs (net benefit = 0.4805 years of perfect life) and a 94% probability of being acceptable using a threshold ICUR of pounds 30,000/QALY. The main cost drivers distinguishing epoetin-alfa from placebo were the costs of drug and patient care due to increased survival.. The available data suggest a high probability of favourable cost-utility outcomes with epoetin-alfa treatment for anaemia in patients with stage IV breast cancer receiving nonplatinum-containing chemotherapy. Additional studies are warranted.

Topics: Adult; Anemia; Antineoplastic Agents; Breast Neoplasms; Cost-Benefit Analysis; Double-Blind Method; Drug Administration Schedule; Endpoint Determination; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Injections, Subcutaneous; Neoplasm Staging; Quality of Life; Recombinant Proteins; Survival Analysis; Time Factors; Treatment Outcome

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

Several recently published studies describe moderate to severe cognitive dysfunction in breast cancer survivors who were treated with adjuvant chemotherapy 1-5 years before undergoing extensive neuropsychological testing. While these studies are hypothesis-generating and preliminary given their small size and retrospective nature, they consistently suggest that between approximately 15% and 25% of chemotherapy-treated breast cancer patients will have evidence of cognitive dysfunction some years after chemotherapy, compared to about 10% of breast cancer survivors who did not receive chemotherapy. Recent preclinical data strongly suggest that erythropoetin is a potent, endogenous neuroprotective agent that prevents neuronal apoptosis from a variety of insults including hypoxia, trauma, subarachnoidal hemorrhage, and encephalitis. Erythropoietin also appears to enhance learning in a mouse spatial learning maze model. We have conducted a pilot study of epoetin alfa versus placebo in early-stage breast cancer patients who received standard adjuvant anthracycline-based chemotherapy to determine the feasibility of administering standardized neurocognitive assessment tests in the oncology practice setting in order to understand whether the Executive Interview 25 test can detect the subtle cognitive impairment in verbal fluency, attention, and short-term memory observed with chemotherapy, and to assess whether epoetin alfa-treated patients have less evidence of cognitive dysfunction during and 6 months after chemotherapy compared with control-treated patients. We report here the preliminary results of this pilot clinical trial.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Asthenia; Breast Neoplasms; Chemotherapy, Adjuvant; Cognition Disorders; Controlled Clinical Trials as Topic; Disease Models, Animal; Epoetin Alfa; Erythropoietin; Female; Humans; Mastectomy; Mice; Mood Disorders; Patient Satisfaction; Pilot Projects; Prognosis; Quality of Life; Recombinant Proteins; Severity of Illness Index; Treatment Outcome

The cost of managing anemia with prophylactic epoetin alfa therapy versus blood transfusions in breast cancer patients receiving combination chemotherapy was studied. A retrospective study of anemia in breast cancer patients treated with four cycles of cyclophosphamide and doxorubicin with fluorouracil (CAF) or without fluorouracil (CA) was conducted. For each cycle of chemotherapy, patients were assessed for fatigue, subsequent blood transfusions administered, and potential response to and adverse effects of blood transfusions. Transfusions were given at the prescriber's discretion rather than in accordance with standard guidelines. The lowest hemoglobin concentration and hematocrit of each patient per cycle were reported. Data on these patients, along with data from published studies of prophylactic use of epoetin alfa, were used in a decision analysis of the costs associated with using epoetin alfa versus red blood cell transfusions to manage anemia. The charts of 50 patients were reviewed. In the study group, the percentage of patients with anemia and the frequency of fatigue rose with each chemotherapy cycle. In general, blood transfusions were not used. The cost of using epoetin alfa prophylactically for all four cycles was estimated at $6483 per patient for the literature-based group versus $169 for the study group. The cost of managing anemia in breast cancer patients was substantially lower when blood transfusions were used than when epoetin alfa was given prophylactically throughout four cycles of therapy with CAF or CA; the absence of standard guidelines for transfusion might have exaggerated the difference in costs.

Topics: Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Decision Trees; Epoetin Alfa; Erythrocyte Transfusion; Erythropoietin; Fatigue; Female; Hematinics; Humans; MEDLINE; Recombinant Proteins; Retrospective Studies

The US Food and Drug Administration (FDA) has approved epoetin and darbepoetin for chemotherapy-induced anemia (CIA). Approved epoetin and darbepoetin dosing schedules were three times per week and weekly, respectively, although off-label, less frequent scheduling was common. In 2004, 2007, and 2008, a US Food and Drug Administration Advisory Committees warned of risks associated with erythropoiesis-stimulating agents. During this period, lawsuits alleging illegal darbepoetin marketing practices have concluded, resulting in $1.1 billion in fines and settlements and one criminal conviction. No prior study, to our knowledge, has reported on the use of darbepoetin versus epoetin for CIA.. We evaluated the dosing, utilization, and costs of erythropoiesis-stimulating agents among 3,761 South Carolina Medicaid patients with CIA.. Epoetin and darbepoetin utilization rates were 22% and 28% in 2003, 10% and 33% in 2007, and 3% and 7% in 2010, respectively. Mean per-patient per-administration epoetin and darbepoetin doses were 40,983 IU and 191 µg, respectively, in 2003 and 47,753 IU and 369 µg, respectively, in 2010. Mean monthly patient costs for epoetin and darbepoetin were $1,030 and $981, respectively, in 2003 and $932 and $1,352, respectively, in 2010. Epoetin use decreased steadily between 2002 and 2010; darbepoetin use increased steadily between 2003 and 2007 and then decreased steadily thereafter. Per-patient dosing of darbepoetin, but not epoetin, increased steadily between 2003 and 2010, and monthly per-patient epoetin costs decreased 3% while the per-patients costs of darbepoetin increased 30% between 2003 and 2010.. To our knowledge, our findings are the first data reporting on epoetin versus darbepoetin use for CIA and support recently concluded lawsuits involving allegations of illegal marketing practices of the manufacturer of darbepoetin.

Topics: Adolescent; Adult; Anemia; Antineoplastic Agents; Breast Neoplasms; Colorectal Neoplasms; Darbepoetin alfa; Drug Utilization; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Logistic Models; Lung Neoplasms; Male; Medicaid; Middle Aged; Recombinant Proteins; South Carolina; United States; Young Adult

Topics: Anemia; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Hematinics; Hemoglobins; Humans; Neoplasms; Quality of Life; Recombinant Proteins; Standard of Care

Several clinical trials in oncology have reported increased mortality or disease progression associated with erythropoiesis-stimulating agents. One hypothesis proposes that erythropoiesis-stimulating agents directly stimulate tumor proliferation and/or survival through cell-surface receptors. To test this hypothesis and examine if human tumors utilize the erythropoietin receptor pathway, the response of tumor cells to human recombinant erythropoietin was investigated in disaggregated tumor cells obtained from 186 patients with colorectal, breast, lung, ovarian, head and neck, and other tumors. A cocktail of well characterized tumor growth factors (EGF, HGF, and IGF-1) were analyzed in parallel as a positive control to determine whether freshly-isolated tumor cells were able to respond to growth factor activation ex vivo. Exposing tumor cells to the growth factor cocktail resulted in stimulation of survival and proliferation pathways as measured by an increase in phosphorylation of the downstream signaling proteins AKT and ERK. In contrast, no activation by human recombinant erythropoietin was observed in isolated tumor cells. Though tumor samples exhibited a broad range of cell-surface expression of EGFR, c-Met, and IGF-1R, no cell-surface erythropoietin receptor was detected in tumor cells from the 186 tumors examined (by flow cytometry or Western blot). Erythropoiesis-stimulating agents did not act directly upon isolated tumor cells to stimulate pathways known to promote proliferation or survival of human tumor cells isolated from primary and metastatic tumor tissues.

Topics: Breast Neoplasms; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Cell Proliferation; Cell Survival; Colorectal Neoplasms; Epidermal Growth Factor; Epoetin Alfa; ErbB Receptors; Extracellular Signal-Regulated MAP Kinases; Female; Hepatocyte Growth Factor; HT29 Cells; Humans; Insulin-Like Growth Factor I; Male; Ovarian Neoplasms; Phosphorylation; Proto-Oncogene Proteins c-akt; Proto-Oncogene Proteins c-met; Receptor, IGF Type 1; Receptors, Erythropoietin; Signal Transduction

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Recombinant Proteins

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Recombinant Proteins

Cognitive dysfunction is a potential side effect of chemotherapy, and erythropoietin might be protective. A previously reported study compared quality-of-life in women undergoing chemotherapy for breast cancer who were randomized to receive epoetin-alpha or standard care. Here, we report a non-randomized sub-study in which cognitive function of participants was evaluated at 12-30 months after chemotherapy.. The primary endpoint was the proportion of women with moderate-severe cognitive impairment, as measured by the High Sensitivity Cognitive Screen (HSCS). Subjects also completed the Revised Hopkins Verbal Learning Test (HVLT-R), the Functional Assessment of Cancer Therapy--Fatigue (FACT-F) and FACT-G self-report questionnaires for fatigue and quality-of-life, and the Hospital Anxiety and Depression Scale.. Of 278 patients receiving adjuvant treatment in the primary study, 87 participated in the sub-study: 45 had received epoetin-alpha and 42 standard care. Groups were well matched for age and type of chemotherapy. Eight patients (9%) had moderate-severe cognitive dysfunction by the HSCS: six of them in the epoietin-alpha group (not significant). There were no significant differences in the HVLT-R, or in fatigue, but patients who had received epoetin-alpha reported better quality-of-life.. This study failed to demonstrate a protective effect of epoetin-alpha against the development of delayed cognitive dysfunction after chemotherapy.

Topics: Antineoplastic Agents; Breast Neoplasms; Case-Control Studies; Cognition Disorders; Epoetin Alfa; Erythropoietin; Fatigue; Female; Hematinics; Humans; Matched-Pair Analysis; Middle Aged; Quality of Life; Randomized Controlled Trials as Topic; Recombinant Proteins

Porphyrias are rare diseases, and for these patients every administration of drugs may induce an acute attack of porphyria. The list of safe compounds allowed in these patients is available for clinicians from specific websites cited in the text.. However, data concerning anticancer therapy in patients with such diseases remain poor. Therefore any publications can help clinicians to deal with this very specific group of patients.. In our institution, three patients received docetaxel and hematologic growth factors (erythropoietin and GCSF) without unexpected toxicities. Aromatase inhibitors (anstrozole and letrozole) were also given in one patient without any related problem.. The present observation adds some useful data for the possible treatment of cancer in patients with porphyria.

Topics: Anastrozole; Antineoplastic Agents; Aromatase Inhibitors; Breast Neoplasms; Docetaxel; Epoetin Alfa; Erythropoietin; Female; Granulocyte Colony-Stimulating Factor; Hematinics; Humans; Letrozole; Middle Aged; Nitriles; Porphyria, Acute Intermittent; Porphyria, Variegate; Recombinant Proteins; Risk Assessment; Taxoids; Triazoles; Uterine Neoplasms

Topics: Breast Neoplasms; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Recombinant Proteins; Survival Rate

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

Anaemia is a common toxicity in cancer patients and epoetins (EPOs) are now an established treatment. The economic profile of EPO treatment was assessed in patients with breast cancer treated by adjuvant-chemotherapy.. Two strategies were compared: without treatment by EPO and with the possible use of treatment by EPO (epoetin alfa) when required. The clinical effectiveness criterion was time adjusted to quality of life and economic data included only direct medical costs.. One hundred ninety-two patients were included. In the group with the strategy containing the possible use of EPO, 45.5% of patients effectively received EPO. A significant difference in the haemoglobin level profile over time was observed which provided a significant overall benefit of 0.0052 (p<10(-4)) quality-adjusted life year (QALY) associated with an extra cost of 1,615 (p<10(-4)). In the base case analysis, the cost per added QALY was estimated as 310,577 with the strategy containing the possible use of EPO.. This robust result seems to be unacceptable, but the only relevant point of discussion might be the level of acceptable incremental cost-effectiveness ratio (ICER) for a patient.

Topics: Adult; Aged; Anemia; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Breast Neoplasms; Chemotherapy, Adjuvant; Cost-Benefit Analysis; Cyclophosphamide; Doxorubicin; Epirubicin; Epoetin Alfa; Erythropoietin; Female; Fluorouracil; France; Hematinics; Hemoglobins; Humans; Infusions, Intravenous; Middle Aged; Quality of Life; Quality-Adjusted Life Years; Recombinant Proteins; Retrospective Studies; Sensitivity and Specificity; Treatment Outcome

Hematopoietic growth factors have played a major role in preventing infection and shortening the duration of neutropenia in patients receiving cancer chemotherapy. Little information is available on how these growth factors are used in patients with cancer outside the clinical trial setting. We performed descriptive and exploratory analyses on the patterns and correlates of the use of hematopoietic growth factors in community-dwelling elderly patients.. We identified 5,843 women from the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked data cohorts who were diagnosed with breast cancer at age 65 or older in 1992 to 1999 from the 11 SEER areas and received chemotherapy.. Overall, 17.3% of the elderly women with breast cancer chemotherapy received filgrastim and 6.8% received epoetin. The use of the growth factors increased significantly over time from 1992 to 1999 (P < .001 for trend). Compared with patients diagnosed in 1992 to 1994, patients diagnosed in 1998 to 1999 were more than five times and 65 times more likely to receive filgrastim and epoetin, respectively, after controlling for other factors such as age and comorbidity. There also was substantial geographic variation in the use of hematopoietic growth factors, ranging from 10.6% in Seattle to 22.9% in Atlanta. Significant predictors of growth factors included patient age, race, tumor stage, and comorbidity.. There were substantial temporal and geographic variations in the use of hematopoietic growth factors among patients receiving chemotherapy for breast cancer. The nationwide and population-based Medicare claims provide potential for examining the effectiveness, medical costs, and cost effectiveness of hematopoietic growth factors in the community.

Topics: Age Factors; Aged; Aged, 80 and over; Breast Neoplasms; Cohort Studies; Epoetin Alfa; Erythropoietin; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematinics; Hematopoietic Cell Growth Factors; Humans; Multivariate Analysis; Neoplasm Staging; Recombinant Proteins; SEER Program; Treatment Outcome; United States

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

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

Breast cancer patients receiving chemotherapy often exhibit anemia, which contributes to symptoms such as fatigue, compromising quality of life (QOL). The present subset analysis assessed the effects of recombinant human erythropoietin (rHuEPO, epoetin alfa) on anemia and QOL in approximately 1300 patients with breast cancer, who were derived from 3 large, community-based clinical trials of epoetin alfa in anemic chemotherapy patients with various malignancies. Epoetin alfa effectively and safely corrected anemia and improved QOL scores on the Linear Analogue Self-Assessment, which measures energy, ability to perform daily activities, and QOL. Clinical, laboratory, and QOL improvements were qualitatively and quantitatively similar to those reported in the larger populations with various tumor types. The efficacy and safety of epoetin alfa did not vary according to dosing frequency (1 vs. 3 times weekly). Epoetin alfa is, therefore, effective and safe in the management of anemia in patients with breast cancer treated with chemotherapy.

Topics: Anemia; Antineoplastic Agents; Breast Neoplasms; Clinical Trials as Topic; Epoetin Alfa; Erythropoietin; Female; Humans; Injections, Subcutaneous; Quality of Life; Recombinant Proteins; Retrospective Studies

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Blood Transfusion, Autologous; Breast Neoplasms; Combined Modality Therapy; Epoetin Alfa; Erythropoietin; Female; Hematinics; Hematopoietic Stem Cell Transplantation; Humans; Middle Aged; Platelet Transfusion; Recombinant Proteins

Topics: Adult; Anemia; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Epoetin Alfa; Erythropoietin; Female; Hematinics; Humans; Recombinant Proteins; Treatment Outcome

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anemia; Blood Transfusion; Breast Neoplasms; Child; Child, Preschool; Combined Modality Therapy; Cost-Benefit Analysis; Epoetin Alfa; Erythropoietin; Female; Humans; Middle Aged; Neoplasms; Recombinant Proteins; Risk Assessment