Iron deficient erythropoiesis might play key role in development of anemia in cancer patients

Introduction

Multifactorial pathogenesis is involved in anemia of cancer patients and defining the causes of anemia is not always simple.

Methods

The incidence of anemia among 4 major cancers (gastric, colorectal, lung cancer and hepatocellular carcinoma), and biochemical features of anemia using ferritin, CRP, hepcidin and soluble transferrin receptor (sTfR) were assessed. Anemia was defined either by hemoglobin (Hb) ≤11 g/dL or a drop of Hb 2 g/dL or more during anticancer treatment.

Results

Among the 345 patients including 152 lung cancer, 101 gastric cancer, 69 colorectal cancer and 23 hepatocellular carcinoma, 49 patients (14.2%) had anemia at their initial diagnosis of cancer. During treatment, 129 (37.4%) experienced anemia, and 34 (26.4%) were treated mostly by transfusion. Biochemical feature of anemia was examined with 39 patients'' samples. When comparing to the reference value from general population, cancer patients showed numerically higher ferritin, sTfR, CRP and hepcidin level. Among the cancer patients, anemic patients had significantly higher ferritin (p = 0.050) and sTfR (p = 0.009) level compared to non-anemic patients.

Conclusion

Anemia is a common issue in cancer patients and is largely undertreated with sub-optimal diagnoses of cause. The rates of anemia increase significantly during anti-cancer treatment and appear to be largely associated with iron deficiency.     

Once-weekly epoetin beta (30,000 IU) in anemic patients with lung cancer receiving chemotherapy

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.     

Once-weekly dosing of epoetin-alpha increases hemoglobin and improves quality of life in anemic cancer patients receiving radiation therapy either concomitantly or sequentially with chemotherapy

BACKGROUND: The current study was performed to prospectively evaluate the effectiveness, clinical outcomes, and safety of once-weekly (QW) recombinant human erythropoietin (r-HuEPO [epoetin-alpha]) in anemic cancer patients with nonmyeloid malignancies who were receiving radiation therapy (RT) concomitantly or sequentially with chemotherapy (CT). METHODS: A total of 777 anemic patients (hemoglobin [Hb] < or = 11 g/dL) were enrolled in this multicenter, open-label, nonrandomized, 16-week study. Patients initially received epoetin-alpha at a dose of 40,000 units (U) subcutaneously QW, escalating to a dose of 60,000 U QW if the Hb increased to < or = 1 g/dL after 4 weeks. Endpoints were changes in hematologic and quality of life (QOL) parameters. RESULTS: Among the 442 patients evaluable for hematologic response, the mean increase in Hb from baseline to the time of final evaluation was 1.9 +/- 1.8 g/dL (P < 0.05). An increase in Hb of > or = 2 g/dL, in the absence of blood transfusions, occurred in 68.3% of patients (278 of 407 patients) who were on the study for > or = 30 days. The overall response rate (Hb increase > or = 2 g/dL or Hb > or = 12 g/dL in the absence of blood transfusions) was 74.0% (301 of 407 patients). In 359 patients who were evaluable for QOL assessment, epoetin-alpha therapy was found to significantly (P < 0.05) improve mean Linear Analog Scale Assessment (LASA) scores for energy level, ability to perform daily activities, and overall QOL from baseline to the time of final evaluation. QW epoetin-alpha therapy was found to be well tolerated. CONCLUSIONS: Treatment with QW epoetin-alpha was found to increase Hb levels, decrease transfusion requirements, and improve functional status and QOL in anemic patients with nonmyeloid malignancies who were receiving RT concomitantly or sequentially with CT. Clinical benefits and the safety profile of QW epoetin-alpha in this setting appear to be similar to those observed in anemic cancer patients receiving CT.     

Prognostic impact of hemoglobin levels on treatment outcome in patients with nasopharyngeal carcinoma treated with sequential chemoradiotherapy or radiotherapy alone

BACKGROUND: The goal of the current study was to investigate the impact of hemoglobin (Hb) levels on treatment outcome in a randomized Phase III trial of patients with nasopharyngeal carcinoma (NPC) treated with induction chemotherapy followed by radiotherapy or with radiotherapy alone. METHODS: Between September 1989 and August 1993, 334 patients with advanced NPC were entered into a randomized trial comparing 3 cycles of induction chemotherapy (cisplatin and epirubicin) followed by radiotherapy with radiotherapy alone. Only evaluable patients who completed radiation were included in the analysis (n = 286). Patients were stratified into normal and low Hb groups according to baseline, preradiation, and midradiation Hb levels. Local recurrence-free, distant metastasis-free, and disease-specific survival rates were estimated using the Kaplan-Meier method. Multivariate analysis was performed using the Cox model. RESULTS: In the chemotherapy arm, the mean baseline, preradiation, and midradiation Hb levels were 13.6, 11.0, and 11.8 g/dL, respectively. In the radiotherapy arm, the mean baseline/preradiation and midradiation Hb levels were 13.7 and 12.9 g/dL, respectively. A midradiation Hb level < or = 11 g/dL was associated with significantly poorer 5-year local recurrence-free (60% vs. 80%; P = 0.0059) and disease-specific survival rates (51% vs. 68%; P = 0.001), with no difference in distant metastasis-free rates (69% vs. 67%; P = 0.83). No significant difference in treatment outcome according to baseline or preradiation Hb levels was noted. Multivariate analysis showed that a low midradiation Hb level, but not a low baseline or preradiation Hb level, was an independent predictor of local disease recurrence and malignancy-related death. CONCLUSIONS: The current study showed that midradiation Hb level was an important prognostic factor with respect to local control and survival in patients with NPC. The high incidence of anemia after chemotherapy has a negative impact on treatment outcome, and this condition may reduce the benefit of induction chemotherapy. Attempts to correct anemia during radiation and the impact of anemia on treatment outcome requires further study.     

Impact of hemoglobin levels before and during concurrent chemoradiotherapy on the response of treatment in patients with cervical carcinoma: preliminary results

BACKGROUND: In patients undergoing radiation for cervical carcinoma, there is evidence that anemia is associated with an impaired outcome. For patients undergoing chemoradiation, there are no data available. The objective of this retrospective study was to examine the impact of anemia before and during chemoradiation in patients with cervical carcinoma. METHODS: The authors collected data on hemoglobin (Hb) levels before and during treatment from 57 patients with cervical carcinoma. The stage of disease ranged between Stage IB and Stage IVA. All patients were treated with concurrent chemoradiation. Response to chemoradiation was evaluated by univariate and multivariate analyses. RESULTS: The mean Hb level at the time of presentation was 12.9 +/- 1.6 g/dL in patients with a complete clinical response (CCR) and 12.1 +/- 1.4 g/dL in those with persistent disease (P = 0.126). In patients with a CCR, the mean nadir Hb level was 11.1 +/- 1.3 g/dL, and in patients with treatment failure, it was 9.8 +/- 1.8 g/dL (P = 0.008). A univariate logistic regression model demonstrated that the nadir Hb level was the most predictive factor for treatment failure (relative risk, 1.92; P = 0.015) followed by disease stage (relative risk, 0.51; P = 0.074). In a multivariate model, the nadir Hb level remained the only prognostically relevant factor predicting the response to chemoradiation. Only patients with nadir Hb values > 11 g/dL throughout chemoradiation had a more than 90% chance of achieving a CCR. CONCLUSIONS: In patients undergoing chemoradiation for cervical carcinoma, the nadir Hb level is highly predictive of response to treatment, whereas the Hb level at the time of presentation is prognostically not significant.     

Assessing symptom burden using the M. D. Anderson symptom inventory in patients with chemotherapy-induced anemia: results of a multicenter, open-label study (SURPASS) of patients treated with darbepoetin-alpha at a dose of 200 microg every 2 weeks

BACKGROUND: Patients with cancer who are receiving chemotherapy often experience chemotherapy-induced anemia (CIA), which is associated with symptoms that reduce quality of life. The M. D. Anderson Symptom Inventory (MDASI) is a brief, self-rating assessment scale that measures the severity of core symptoms and symptom interference with function. The current study used the MDASI to prospectively assess the correlation between hemoglobin and self-perceived cancer-related symptoms in a large patient population with CIA who were receiving darbepoetin-alpha at a dose of 200 mug every 2 weeks. METHODS: Eligible patients enrolled in this multicenter, open-label study were age > or =18 years, had a nonmyeloid malignancy, were receiving multicycle chemotherapy, and were anemic (hemoglobin < or = 11 g/dL). Hemoglobin was measured every 2 weeks; the MDASI was administered weekly. For hemoglobin-based endpoints, patients were stratified by baseline hemoglobin (< 10 g/dL or > or =10 g/dL). RESULTS: Of 2422 enrolled patients, 2401 received > or =1 dose of darbepoetin-alpha. Eighty percent of patients (95% confidence limit, 78-82 patients) achieved target hemoglobin levels (> or =11 g/dL) during the study. Patients with a baseline hemoglobin < 10 g/dL had a greater increase in hemoglobin, took longer to achieve the target hemoglobin, and received more red blood cell transfusions than patients with a baseline hemoglobin > or =10 g/dL. The percentage of patients with moderate to severe MDASI scores (> or =5 points) for fatigue, distress, loss of appetite, disturbed sleep, and interference with function was reduced during the study. Improvement in symptom burden was associated with an increase in hemoglobin concentration. CONCLUSIONS: Treatment with darbepoetin-alpha at a dose of 200 mug every 2 weeks is associated with improvement in symptom burden as measured by the MDASI, a simple tool that may improve symptom management for cancer patients with CIA.     

What is the value of hemoglobin as a prognostic and predictive factor in cancer?

Anemia is a frequently encountered complication in cancer, and is associated with fatigue and reduced quality of life. Retrospective analyses of data from patients with hematological malignancies and solid tumors provide evidence that a low baseline hemoglobin (Hb) level is a prognostic factor for poor outcome. Moreover, in some situations, low Hb is a negative predictive parameter in chemotherapy. The adverse impact of anemia has been documented in patients with lymphomas and leukemias, as well as in those with non–small-cell lung cancer, ovarian cancer, cervical cancer, renal cell carcinoma, head and neck cancer and other solid tumors. Studies in animal models support the role of low Hb levels as a negative prognostic and predictive factor. Although prospective clinical trials are still needed to confirm that Hb levels affect outcome, the available evidence suggests that there is more than one reason to pay attention to Hb levels in cancer patients: increasing Hb not only corrects anemia and thereby improves physical functioning and quality of life, but also may improve clinical outcomes.     

Response predicting factors to recombinant human erythropoietin in cancer patients undergoing platinum-based chemotherapy

BACKGROUND: The response to epoetin-alpha treatment is hard to predict in cancer patients receiving chemotherapy. METHODS: One hundred and seventeen patients were enrolled in this observational study. They had a hemoglobin (Hb) level less than or equal to 10.5 g/dL, were receiving platinum chemotherapy with three cycles pending, and they did not have an iron deficiency or hemolysis. Epoetin-alpha was administered subcutaneously three times a week at a dose of 150 IU/kg. Ninety patients were examined. RESULTS: Response was defined as an increase in Hb of at least 2 g/dL during the treatment period. The response rate was 63.3%. The following data were compared between responders and nonresponders at the onset of treatment and after 2 and 4 weeks of epoetin therapy: Hb, reticulocytes, serum iron, ferritin, transferrin, transferrin saturation index, and endogenous erythropoietin levels. At baseline, these variables were similar for responders and nonresponders; after 2 weeks, responders showed higher Hb (P = 0.001) and transferrin levels (P = 0.042) and reticulocyte counts (P = 0.003); after 4 weeks, only the Hb level showed a significant difference (P < 0.0005). Changes from baseline in Hb level after 2 and 4 weeks correlated significantly (P < 0.01) with response. The change in Hb level at Week 4 was the best predictor. A change in Hb level of less than 0.5 g/dL was associated with a lack of response (predictive power, 71%); a change in Hb greater than or equal to 0.5 g/dL was associated with response (predictive power, 89%). CONCLUSIONS: Response to epoetin-alpha treatment in cancer patients receiving platinum chemotherapy can be predicted from changes in Hb level after 4 weeks of therapy.     

Management of cancer-related anemia in patients with breast or gynecologic cancer: new insights based on results from the European Cancer Anemia Survey

The incidence, prevalence, and treatment of anemia (hemoglobin [Hb] <12 g/dl) in women with breast cancer and gynecologic cancer were evaluated using data from the European Cancer Anemia Survey (ECAS). Adult patients with newly diagnosed treated or untreated disease, persistent/recurrent disease, and disease in remission were enrolled and followed for up to six chemotherapy cycles or six evaluation points within a 6-month period. At enrollment, 30.4% of breast cancer patients and 49.1% of gynecologic cancer patients were anemic. A significant correlation was shown between low Hb level and poor performance status (World Health Organization criteria) at enrollment for both breast cancer and gynecologic cancer patients. In all, 62.4% of breast cancer patients and 81.4% of gynecologic cancer patients were anemic at some time during the survey. The incidence of anemia, determined in a carefully defined population, was 59.8% for breast cancer patients and 74.8% for gynecologic cancer patients. Despite the high prevalence and incidence of anemia, only 26.3% and 42.7% of patients in the respective groups received anemia treatment. In breast cancer patients, the mean Hb trigger was 10 g/dl for epoetin treatment and 8.6 g/dl for transfusion; corresponding values for gynecologic cancer patients were 10.1 g/dl and 9.1 g/dl. Logistic regression analyses in the overall ECAS population identified five factors as significant and suitable predictors of anemia: lower initial Hb, having lung or gynecologic cancer versus gastrointestinal/colorectal cancer, any other cancer versus gastrointestinal/colorectal cancer, treatment with platinum chemotherapy, and being female. The ECAS data highlight the need for greater awareness of the adverse impact of anemia on cancer patients and for optimal anemia management to ensure maximal patient quality of life.     

The impact of anemia on outcome of chemoradiation for limited small-cell lung cancer: a combined analysis of studies of the National Cancer Institute of Canada Clinical Trials Group.

BACKGROUND: Associations between anemia and outcomes of chemoradiation have been documented in several malignancies, but few data exist for limited small-cell lung cancer (LD-SCLC). This combined analysis of 652 patients in two randomized clinical trials in LD-SCLC carried out by the National Cancer Institute of Canada Clinical Trials Group was undertaken to explore the relationship between anemia at baseline and anemia arising during therapy, and outcomes of chemoradiation in this cancer. PATIENTS AND METHODS: The relationships between overall survival and local control with hemoglobin levels at baseline and those arising during therapy (nadir hemoglobin (Hb) and maximum percentage drop from baseline values) were explored. RESULTS: No Hb parameter was associated with either outcome. Baseline anemia was found in one-third of patients, was more common in males, in those with a poorer performance status and those with an elevated lactate dehydrogenase; all of these latter factors were associated with shorter survival. A trend towards improved local control in patients with the greatest drop in their Hb did not remain significant in a multivariate analysis. CONCLUSIONS: Anemia is common in patients with LD-SCLC. Anemia at diagnosis may have a different prognostic implication than that arising during therapy, and correction of anemia may have no impact on outcomes.     

PITASOR epidemiological study: prevalence, incidence and treatment of anaemia in radiation therapy oncology departments in Spain

Introduction

Anemia is the most common haematological complication in cancer patients.

Objective

Analysis of the incidence, prevalence and treatment of anemia in oncologic patients treated in Radiation Oncology Departments in Spain (ROD) and monitoring of the existing recommendations for the treatment of anemia.

Material and methods

Observational, prospective, multicenter study which involved 19 Spanish ROD. The study was approved by the CEIC Central Defense Hospital. 477 patients with solid tumors, subsidiary of RT with radical intent referred to such centers within a period of one month (5/5/09 to 5/6/09) and gave their consent to participate in the study. We gathered the main characteristics of patients and their oncologic disease. All patients underwent a determination of Hb levels before RT, upon reaching 25–35 Gy and at the end treatment. In patients with anemia we assessed the existence of related symptoms and its treatment.

Results

Basal situation: The prevalence of anemia was 34.8% (166 patients). Mean Hb in patients with anemia was 11.17±1.07 g/dl. Anemia-related symptoms were present in 34% of the patients. Anemia predisposing factors were: stage of the disease, previously received chemotherapy, and hormonal therapy. 39% (66 patients) received anemia treatment, with a mean Hb of 10.43±1.04 g/dl. During RT: The prevalence of anemia was 38.9% (182 patients) with a mean Hb of 11.24±1.21 g/dl. Predisposing factors for anemia during RT treatment were: age, male sex, chemotherapy prior to RT, basal anemia and chemotherapy during RT. 36.3% (66 patients) had anemia-related symptoms. 34.6% (63 patients) with a mean Hb of 10.5±1.37 g/dl received treatment for anemia. The prevalence of anemia at the end of the RT was 38.1% (177 patients) with a mean Hb of 11.19±1.18 g/dl. The predisposing factors for the appearance of anemia at the end of RT were: male sex, anemia at basal situation and during treatment and chemotherapy during RT. 34% (61 patients) had anemia-related symptoms and 73 patients (41.2%) with a mean Hb of 10.5±1.22 g/dl received treatment for anemia. The presence of anemia-related symptoms was significantly correlated with the beginning of treatment for anemia. The incidence of anemia (new cases) during radiotherapy was 17.5%.

Conclusion

The prevalence of anemia in basal situation, during RT and at the end of RT is 34.8%, 38.9% and 38.1%. During RT the incidence of anemia is 17.5%. 39.8%–41.2% of patients with anemia and 64.2%–68% of patients with anemia-related symptoms received treatment. Treatment of anemia starts with Hb<11 g/dl and the goal is to achieve Hb 12 g/dl. In our Radiotherapy Oncology Departments, the treatment of anemia complies with the current recommendations and guidelines in use.     

Severity, risk factors, and physician practices in the management of anemia during concurrent chemoradiation for head and neck carcinoma

BACKGROUND: Anemia is a well-recognized complication of concurrent chemoradiation therapy for head and neck carcinoma. It impairs quality of life and many studies also have reported an association between anemia and increased tumor recurrence and decreased long-term survival. In the current study, the authors attempted to identify the severity, risk factors, and physician practices in the management of anemia. METHODS: Medical records of those patients receiving concurrent chemoradiation for head and neck carcinoma between 1999-2003 were reviewed. The average weekly nadir hemoglobin level (AWNH) was defined as the mean value of the lowest hemoglobin concentration in each week. Independent predictors for an AWNH < 11 g/dL were identified using multivariable logistic regression analyses. RESULTS: Seventy-two patients were included in the current study, 66.7% of whom had unresectable disease. The overall median survival was 402 days. At baseline, 76.4% (95% confidence interval [95% CI], 66.3-86.4%) of patients already had a hemoglobin level < 13.5 g/dL. The hemoglobin level dropped 2.5 +/- 1.9 g/dL during concurrent chemoradiation, resulting in 95.8% of patients having a hemoglobin level < 13.5 g/dL at the end of the observation period. Blood was transfused to 24 patients (33.3%); erythropoietin or darbepoietin was administered to 2 patients (2.7%). The mean lowest hemoglobin threshold of transfusion was 7.3 +/- 1.0 g/dL. The cumulative percentage of patients who received a transfusion reached 50% when the mean nadir hemoglobin level was 7.4 g/dL. Independent predictors of an AWNH < 11.0 g/dL were low baseline hemoglobin and receiving multiple concurrent chemotherapeutic agents, with relative risks of 13.6 and 1.8, respectively (95% CI,1.9-93.9 and 1.1-3.1, respectively). CONCLUSIONS: Anemia is prevalent in patients undergoing treatment for head and neck carcinoma and can be severe with concurrent chemoradiation therapy. However, the intensity of anemia management is low. A low baseline hemoglobin level and the reception of multiple concurrent chemotherapeutic agents are considered to be the main risk factors of anemia. Cancer 2006.     

A new induction schedule of epoetin alfa 40.000 IU in anemic patients with advanced lung cancer

BACKGROUND: 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. OBJECTIVE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Cancer-related anemia

Anemia has a high prevalence in patients with cancer. Its frequency and severity depend on tumor type, tumor stage, duration of disease, and treatment status. The etiology of cancer-related anemia is multifactorial and includes myelotoxicity of treatment, bone marrow infiltration, impaired erythropoietin production, blood loss, and the anemia of chronic disease. Anemia affects health-related quality of life (QOL) and may impact on tolerance or even outcome of anticancer therapy. Despite its high prevalence and impact on QOL, anemia is often under-recognized and under-treated. Treatment should correct etiologic factors, whenever possible. Symptomatic treatments are red blood cell transfusions and administration of erythropoietic growth factors. Transfusions result in rapid improvement of anemia-related symptoms but are usually only given to patients with moderate to severe anemia. Administration of epoetins (epoetin alfa, epoetin beta) or darbepoetin alfa increases hemoglobin levels, reduces the need for blood transfusions, and improves QOL in patients with cancer-related anemia. Trials determining the exact association of anemia with both response to chemo(radio)therapy and survival are ongoing. Physicians should be aware of the clinical relevance of and treatment options for anemia in cancer patients.     

Epoetin alfa therapy for patients with hematologic malignancies and mild anemia

Anemia has been reported in approximately 40%-70% of patients with hematologic malignancies, with severity depending on the type and stage of disease and whether the patient has received myelosuppressive chemotherapy. Growing evidence supports the role of epoetin alfa in correcting anemia and improving quality of life (QOL) in patients with hematologic malignancies. Clinical practice guidelines recommend the use of epoetin alfa in patients with cancer-related anemia (including patients with hematologic malignancies) and hemoglobin levels < or =10 g/dL. Epoetin alfa treatment is optional for patients with cancer-related anemia and hemoglobin levels>10 g/dL and <12 g/dL, depending on clinical circumstances. A prospective, open-label, randomized trial evaluating hematologic response, transfusion use, and QOL after immediate or delayed epoetin alfa treatment in mildly anemic patients (hemoglobin< or =12 g/dL) undergoing chemotherapy for chronic lymphocytic leukemia, multiple myeloma, or lymphoma was recently completed. Study objectives included determining any correlation between changes in hemoglobin level and QOL and assessing any correlation between QOL measures and health care resource use. Interim results suggest that epoetin alfa treatment in patients with hematologic cancers and hemoglobin< or =12 g/dL who are receiving chemotherapy increases hemoglobin, functional capacity, well-being, work and productivity, and health resource use. Further evaluation of alternative epoetin alfa dosing schedules and use of epoetin alfa in treating anemia in patients with specific hematologic malignancies is ongoing.     

A phase I/II study of pemetrexed and vinorelbine in patients with non-small cell lung cancer

The often-aggressive therapy, including platinum-based regimens, required to treat lung cancer patients results in a significant risk for anemia in this population. Results of the recent European Cancer Anaemia Survey (ECAS) showed that, at enrollment, 37.6% (753/2002) of lung cancer patients were anemic; rates by cancer treatment were 50.0% on concomitant chemotherapy/radiotherapy, 39.0% on chemotherapy, 31.7% on radiotherapy, 38.6% on combination treatment, and 30.7%, on no treatment. At enrollment, of 605 patients receiving platinum therapy, 50.1% were anemic versus 30.6% of 1252 receiving nonplatinum regimens. During ECAS, 83.3% of lung cancer patients who received chemotherapy were anemic at some time, with the prevalence of anemia in platinum-treated patients increasing progressively from 23.5% at Cycle 1 to 77.3% at Cycle 6 (corresponding values for nonplatinum-treated patients, 32.9% and 57.7%). However, only 47% of anemic patients received anemia treatment, which, when provided, often was not initiated until hemoglobin (Hb) levels were relatively low (initiation Hb: epoetin, 9.1 g/dL; transfusion, 8.5 g/dL). Logistical analysis of ECAS data identified treatment with platinum, female sex, and initial Hb level as risk factors for anemia in lung cancer patients. Given the potential adverse consequences of anemia in lung cancer patients, including diminished quality of life (QOL), it is advisable that treatment patterns for anemia management, especially in regard to anemia monitoring and Hb level used to initiate treatment, be reviewed and optimized, with the goal of optimizing overall patient care. Also, anemia risk factors should be considered, which may help clinicians identify lung cancer patients particularly at risk for this problem, allowing the planning and initiation of appropriate treatment for effective and timely anemia management, thus preserving patient QOL.     

重组人红细胞生成素大剂量冲击维持疗法治疗30例肿瘤相关贫血的临床报告

背景与目的:贫血是癌症患者常见的并发症,重组人红细胞生成素(recombinanthumanerythropoietin,rhEPO)的应用能改善癌症贫血患者的症状,但其最佳使用方法仍在探讨之中。为探索rhEPO在肿瘤相关贫血患者中的最佳用药方案,本研究在同期接受化疗的癌症贫血患者中进行了rhEPO冲击维持疗法的临床应用研究。方法:采用开放性非随机的临床研究方法,选取2004年5月至2005年2月30例同期接受化疗且伴随贫血的恶性肿瘤患者,第1周采用rhEPO120000U冲击用药(40000U皮下d1,3,5),然后rhEPO每周40000U皮下维持用药,共3周(d8,15,22);比较治疗前及治疗开始后每2周的血红蛋白(Hb)水平和红细胞压积(Hct)值。结果:入组患者给予rhEPO后Hb水平呈持续上升趋势,在治疗后第2周及第4周Hb比基础值(79.56g/L)上升≥20g/L的患者分别占27.59%和61.90%;第2周(n=29)及第4周(n=21)Hb的平均值分别为90.26g/L和96.81g/L,与治疗前相比差异均具有显著性(P<0.05);第2周及第4周Hct的平均值分别为27.01%和30.17%,与治疗前(24.29%)相比也有所提高(P=0.062,P=0.001)。所有患者均耐受良好。结论:在恶性肿瘤贫血患者中使用rhEPO大剂量冲击维持疗法,可有效快速提高患者的血红蛋白水平,改善患者的贫血状况,该疗法耐受性较好,值得进一步扩大临床研究。     

Targeted molecular mechanisms of epoetin alfa

Despite therapeutic improvements and ongoing efforts to develop more efficacious therapies, the majority of lung cancer patients face a poor prognosis. Therefore, the primary goal of current treatment is palliation, improvement and maintenance of quality of life (QOL), and (modest) prolongation of survival. Anemia frequently occurs in lung cancer patients and has been associated with decreased QOL, impaired treatment outcomes, and shortened survival time. Furthermore, anemia is a causative factor of tumor hypoxia, which compromises the efficacy of chemotherapy and radiotherapy. Thus, correction of even mild anemia seems to have a beneficial effect on QOL and cancer treatment outcomes. The current article describes the basis and mechanism for the use of recombinant human erythropoietin (rHuEPO, epoetin alfa), a molecular targeted therapy, for the treatment of cancer-related anemia, with a focus on lung cancer. Epoetin alfa has proven efficacy and safety in correcting anemia and improving QOL based on numerous clinical studies and over a decade of clinical practice. In addition, emerging data show that epoetin alfa may offer potential benefits beyond treating anemia, specifically in terms of treatment outcomes and cognitive function. Future research needs to be conducted to explore the potential for epoetin alfa to improve survival time in lung cancer patients.     

Epoetin-alpha during radiotherapy for stage III esophageal carcinoma

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

Darbepoetin alfa: potential role in managing anemia in cancer patients

Anemia in cancer patients is frequent but often under-recognized and under-treated. This may be related to misconceptions about the impact of anemia on cancer patients and ill-defined guidelines for treatment, as well as the inadequacies of current therapy. Darbepoetin alfa, a novel erythropoiesis-stimulating protein with a longer serum half-life than epoetin (α and β), is approved to treat anemia in patients with chronic kidney disease. Most recently darbepetin alfa has received approval by the FDA in USA for the treatment of anemia associated with myelosuppressive chemotherapy and approval in the EU is expected soon. Clinical trials in cancer patients indicate that darbepoetin alfa effectively and safely alleviates anemia in patients receiving chemotherapy. A Phase II trial also indicates that darbepoetin alfa is effective in patients who are not receiving chemotherapy. Thus, darbepoetin alfa has the potential to improve supportive care and thereby, cancer patients’ quality of life, and might also impact on treatment outcome.