促红细胞生成素防治肺癌化疗所致贫血临床研究

目的 评价促红细胞生成素(epoetin alfa,EPO)对接受化疗的肺癌患者血红蛋白(hemoglobin,Hb)、输血需求以及生存质量(quality of life,QOL)的影响.方法 将77例Hb≤120 g/L的肺癌患者随机分为两组治疗组接受EPO 30 000 U/次,皮下注射,每周1次,持续8周(EPO组);对照组采用最佳支持治疗(best supportive care,BSC)(BSC组).观察两组化疗期间Hb变化、输血需求、QOL及不良反应情况.结果 在整个治疗过程中EPO组的平均Hb水平保持在120 g/L以上,而BSC组的平均Hb下降.EPO组的Hb反应率为54.5%,明显好于BSC组7.7%(P＜0.0001).EPO组和BSC组的输血需求分别为7.9%、30.8%(χ2=6.307,P＜0.05).8周时,EPO组的FACT-An贫血及乏力平均分数变化分别为2.20±11.93、3.61±10.48,BSC组分别为-4.37±12.84、-5.29±11.09(P＜0.0001).两组的不良反应相似.结论 EPO 3 000 U每周1次能有效保持肺癌化疗患者的Hb水平,减少输血需求,提高生存质量.     

促红细胞生成素预防肿瘤化疗相关贫血的疗效观察

目的探讨重组人红细胞生成素(rhEPO)在预防含铂方案化疗相贫血中的作用。方法选择93例进展期恶性肿瘤患者随机分组:化疗+rhEPO组45例和单纯化疗组48例。2组均接受含铂剂为主联合方案化疗。分别于化疗后4周、8周、16周评估血红蛋白水平,治疗开始前及治疗16周后评估体力状况评分(KPS),应用癌症患者生活质量评估量表(QLQ-52)对患者的总体生活质量进行评估。结果化疗+rhEPO组化疗前Hb水平为(124.0±9.8)g/L,完成4个周期化疗后Hb水平为(120.0±11.0)g/L,差异无显著意义(P>0.05)。单化疗组化疗前Hb水平为(126.0±12.0)g/L,完成4个周期化疗后平均Hb水平为(98.0±10.2)g/L,其中23例患者Hb水平<100 g/L。与化疗前比较,具有非常显著性差异(P<0.01)。生活质量调查分析显示,单化疗组化疗前QOL评分为(90±34)分,完成4个周期化疗后QOL评分为(106±40)分,总体生活质量受到显著影响(P<0.05);联合治疗组患者生活质量评分无明显变化(P>0.05)。结论化疗联用rhEPO即能有效维持肿瘤患者的Hb水平,可预防并延缓化疗造成的贫血的发生,又能维持良好的生活质量,安全可靠。     

三氧化二砷治疗初治急性早幼粒细胞白血病疗效分析

 目的　分析以三氧化二砷（ATO）为基础的诱导和维持治疗方案治疗初发急性早幼粒细胞白血病（APL）的长期疗效。方法　回顾性分析62例初诊成年APL患者诱导缓解治疗和缓解后巩固维持治疗经过,并作5、7年随访分析。结果　诱导治疗阶段,ATO+全反式维甲酸（ATRA）双药联合化疗组与ATRA联合化疗组完全缓解（CR）率差异无统计学意义,但前者达到CR时间明显缩短。诱导治疗后PML-RARα融合基因转阴率两组分别为86.2 %、56.3 %,差异有统计学意义（P＜0.05）。巩固维持治疗阶段,ATO序贯维持组和化疗序贯维持组5年总生存（OS）率分别为（94.4±5.4）%和（45.5±10.2）%,7年OS率分别为（52.5±23.7）%和（27.3±9.3）%;两组5年无病生存（DFS）率分别为（94.7±5.5）%和（41.3±10.1）%,7年DFS率分别为（52.6±23.7）%和（27.5±9.4）%,两组差异有统计学意义（P＜0.05）。并且,ATO序贯维持组复发率（14.7 %）低于化疗序贯维持组（37.0 %）,差异有统计学意义（P＜0.05）。结论　以ATO联合ATRA、化疗的诱导化疗方案可缩短诱导化疗时间,提高PML-RARα融合基因转阴率,而且,包含ATO的序贯维持治疗明显改善APL患者的长期生存,减少复发,安全性高,患者耐受性好。     

贫血对乳腺癌辅助化疗疗效和预后的影响

目的探讨血红蛋白（Hb）水平下降对乳腺癌辅助化疗疗效和预后的影响,以提高患者的疗效和生存质量（QOL）。方法回顾我院近5年213例乳腺癌患者辅助化疗前后血红蛋白水平的变化,按每周期化疗前Hb测定值的平均值是否小于110 g/L为界,将患者分为贫血组与非贫血组,分析其与疗效、预后的关系。结果随着化疗周期增加,Hb呈下降趋势。贫血组的局部复发率（26.4%）高于非贫血组（12.8%）,P=0.013;贫血组的远处转移率较非贫血组有增高趋势,但未达到显著性差异（P〉0.05）。贫血组乳腺癌患者的5年无病生存率（DFS）（33.3%）显著低于非贫血组乳腺癌（60.3%）,P〈0.001,分层分析显示贫血对淋巴结阳性组5年无病生存率（DFS）和总生存率（OS）影响均有统计学意义（P〈0.001;P=0.044）。Cox回归分析显示年龄、淋巴结状态和Hb水平是无局部复发生存的独立影响因素（P〈0.05）。结论贫血降低乳腺癌患者辅助化疗的疗效,是影响预后的独立因素。     

自体和半相合异体细胞因子诱导的杀伤细胞联合化疗治疗非小细胞肺癌的临床疗效评价

 目的　评价自体和半相合异体细胞因子诱导的杀伤（CIK）细胞联合化疗治疗非小细胞肺癌（NSCLC）的临床疗效及安全性。方法　选择42例NSCLC患者为研究对象,按照成组匹配原则将病例分为3组：自体CIK细胞联合化疗组（自体CIK组）,半相合异体CIK细胞联合化疗组（异体CIK组）,单纯化疗组。观察自体和异体CIK细胞免疫治疗的安全性,流式细胞术（FCM）分析比较各治疗组治疗前后体内T细胞亚群变化,并对3组的临床近期疗效进行比较。结果　FCM检测结果显示,自体与异体CIK组CIK细胞输注后CD+3、CD+4／CD+8比值、NK细胞（CD-3 CD+56）和CIK细胞（CD+3 CD+56）比例较治疗前明显升高,自体CIK组治疗前分别为（47.2±10.1）%、1.0±0.1、（15.1±2.7）%、（0.7±0.2）%。治疗后分别为（58.8±12.3）%、1.3±0.2、（24.6±7.1）%、（3.8±2.2）%;异体CIK组治疗前为（49.4±11.4）%、0.9±0.2、（14.8±3.2）%、（0.9±0.3）%,治疗后为（57.3±9.2）%、1.4±0.3、（25.4±6.7）%、（4.3±2.6）%,差异有统计学意义（t值分别为22、20、19,均P＜0.05）,而单纯化疗组治疗前后T细胞亚群水平未见明显改变。临床近期疗效比较结果显示,自体及异体CIK细胞治疗组客观有效率和疾病控制率（分别为35.7 %、28.6 %和64.3 %、71.4 %）均稍高于单纯化疗组（21.4 %、57.1 %）,但差异无统计学意义（χ2＝38.85、χ2＝41.24,均P＞0.05）。结论　自体或半相合异体CIK细胞免疫治疗安全性好、毒副作用低,有一定的近期疗效,可有效延缓肿瘤复发,是一种值得在临床上推广的肿瘤辅助治疗模式。     

多发性骨髓瘤不同分期C-反应蛋白、血红蛋白、红细胞沉降率检测的临床意义

 【摘要】　目的 探讨多发性骨髓瘤（MM）中C-反应蛋白（CRP）、血红蛋白（Hb）、红细胞沉降率（ESR）3项指标的变化及其临床意义。方法 选取新诊断的30例MM患者,记录首次入院的实验室检查指标及临床指标,行国际分期体系（ISS）分期。以同期住院的30例年龄、性别、Hb相仿的巨幼细胞贫血（MA）患者作为对照组。对比不同ISS分期MM中CRP、Hb、ESR的差异,并分析3个指标与肿瘤细胞比例、 β2-微球蛋白（β2-MG）的相关性。结果 MM组Ⅲ期患者CRP、Hb、ESR分别为（24.17±9.87）mg／L、（71.72±13.27）g／L、（105.94±27.73）mm／h,Ⅰ、Ⅱ期分别为（8.54±1.97）mg／L、（91.00±9.92） g／L、（67.00±15.56） mm／h和（14.89±5.51）mg／L、（91.29±8.32） g/L、（73.57±20.53） mm／h,Ⅲ期与Ⅰ、Ⅱ期比较,差异均有统计学意义（均P＜0.05）。MM组CRP、ESR分别为（19.40±10.17） mg／L、（91.90±29.70）mm／h,MA组分别为（7.52±1.57）mg／L、（20.20±8.04）mm／h,差异均有统计学意义（均P＜0.05）。MM患者CRP、Hb、ESR与肿瘤细胞比例、β2-MG有一定相关性（均P＜0.05）。结论　MM病情发展与CRP、Hb、ESR有密切关系,CRP、Hb相对ESR对疾病反应敏感,联合检测3项指标对于观察患者病情进展有明显的临床意义。     

细胞因子诱导激活的杀伤细胞联合化疗治疗晚期结直肠癌的临床观察

 目的 评价细胞因子诱导的杀伤细胞（CIK）联合化疗治疗晚期大肠癌的临床疗效。方法 取外周血50 ml,分离单个核细胞,体外经IL-2、IFN-γ、抗CD3单抗、IL-1刺激培养8天后获得CIK细胞。CIK联合化疗组、行单纯化疗的同期配对晚期大肠癌组患者各50例,比较近期疗效及生存率,流式细胞术检测回输CIK前后患者免疫学指标,并观察其生活质量改善情况及不良反应。结果 CIK细胞治疗前患者外周血中CD3+、CD4+、CD8+和NK细胞比例分别为54.779±14.228%、30.821±11.554%、16.676±6.256%、18.705±9.347%,治疗后分别为65.236±14.901%、37.292±8.880%、25.229±6.711%、22.950±8.9323%,较治疗前均显著提高(P<0.05);CIK联合化疗组患者生活质量明显改善,不良反应轻微;CIK联合化疗组的疾病控制率(DCR)率为64%（32/50）高于单纯化疗组的40%（20/50）(P<0.05),CIK联合化疗组与单纯化疗组生存率差异无统计学意义（P＞0.05）。结论 CIK联合化疗可增强晚期大肠癌患者免疫功能,提高患者生活质量,有较好的临床疗效。     

外周血中性粒细胞与淋巴细胞比率和血小板与淋巴细胞比率对乳腺癌新辅助化疗疗效的预测价值

摘 要：［目的］ 评价外周血中性粒细胞与淋巴细胞比率（NLR）和血小板与淋巴细胞比率（PLR）对乳腺癌新辅助化疗疗效的预测价值。［方法］ 回顾性分析394例接受新辅助化疗（NAC）乳腺癌患者治疗前血液NLR、PLR分布情况,采用受试者工作特征曲线（ROC）法评估NLR、PLR对NAC疗效达病理完全缓解（pCR）的预测价值。［结果］ NAC后pCR率为17.0%,pCR组NLR、PLR分别为1.64±0.5、120.7±37.7,非pCR组分别为2.4±1.1、142.0±46.2,组间差异有统计学意义（P﹤0.001）;NLR、PLR鉴别pCR的受试者工作特征曲线（ROC）的曲线下面积（AUC）分别为0.75、0.64;NLR（≥1.6）、PLR（≥120.7）预测乳腺癌NAC后pCR率的敏感性分别为76.8%、62.6%,特异性分别为60.3%、62.6%;二分类Logistic回归分析显示NLR水平是NAC疗效的独立预测因素。［结论］ 治疗前外周血高水平NLR预示乳腺癌NAC后的pCR率更低。     

沙利度胺治疗急性白血病的疗效及对血管调控因子水平的影响

 目的　观察沙利度胺联合化疗治疗急性白血病的临床疗效及其对血浆血管内皮生长因子（VEGF）、血管内皮生长因子受体（VEGFR）、碱性成纤维细胞生长因子（bFGF）水平的影响。方法　急性白血病患者36例,随机分为试验组及对照组各18例。每组均予以常规化疗方案标准剂量化疗,试验组同时口服沙利度胺100 mg／d。治疗前及治疗后8周分别采集外周血,双抗体夹心酶联免疫吸附法（ELISA）检测血浆VEGF、VEGFR、bFGF含量。以15位健康体检者为健康对照组。结果　试验组与对照组有效率分别为88.9 %（16／18）和77.8 %（14／18）,差异有统计学意义（χ2＝4.103,P＜0.05）。试验组与对照组治疗前血浆VEGF水平分别为（389.78±249.94）和（318.54±125.78 ）pg／ml,高于健康组的（132.91±26.66）pg／ml（t＝3.141、3.024,均P＜0.01）;治疗后分别为（211.74±36.72 ）和（288.02±31.77）pg／ml,高于健康组（t＝2.413、2.324,均P＜0.05）;试验组与对照组治疗前VEGF差异无统计学意义（t＝1.384,P＞0.05）,治疗后差异有统计学意义（t＝2.793,P＜0.05）。试验组与对照组治疗前血浆VEGFR水平分别为（2490.75±1695.9）和（2322.78±1105.87）pg／ml,高于健康组的（1134.98±378.45）pg／ml（t＝2.914、2.783,均P＜0.01）;治疗后分别为（1359.71±390.24 ）和（1753.89±337.04）pg／ml,与健康组相比差异有统计学意义（t＝2.572、2.447,均P＜0.05）;试验组与对照组治疗前VEGFR差异无统计学意义（t＝1.276,P＞0.05）,治疗后差异有统计学意义（t＝2.486,P＜0.05）。试验组与对照组治疗前血浆bFGF水平分别为（2.43±0.27）和（2.41±0.33）ng／ml,高于健康组的（1.83±0.44）ng／ml（t＝4.982、4.171,均P＜0.05）;治疗后分别为（2.09±0.17）和（2.11±0.31）ng／ml,与健康组相比差异有统计学意义（t＝3.011、2.773,均P＜0.05）;试验组与对照组治疗前及治疗后相比差异无统计学意义（t＝0.953、1.282,均P＞0.05）。结论　沙利度胺联合化疗可提高急性白血病患者的缓解率,有可能成为一种通过抗血管新生从而抑制白血病细胞生长及浸润的有效治疗方法。     

晚期肺鳞癌超分割放疗结合化疗的Ⅰ／Ⅱ期临床研究

目的:探讨晚期非小细胞肺癌超分割放疗结合全身化疗的疗效和适应证;方法:64例晚期非小细胞肺鳞癌患者随机分为超分割放疗结合化疗（A组,n=33）和单纯超分割放疗（B组,n=31）二组治疗。资料分析时依据影响本组生存的危险因子将入组病例回顾性评估为“高危”和“低危”二类,“高危”类33例中,接受了超分割放疗结合化疗者16例（C组）,仅接受单纯超分割放疗者17例（D组）;“低危”类31例中,接受超分割放疗结合化疗者17例（E组）和单纯超分割放疗者14例（F组）。随访资料采用“SPSS7.5”统计学软件分析。结果:A组的13、36和47个月生存率分别为56.25％、26.5和13.26％,中位生存期（18.00±6.19）月,B组的13、36和47个月生存率分别为47.23％、22.14％和11.07％,（中位生存期13.00±2.43月,P=0.4563）;E组的15和47个月生存率分别为43.65％和21.83％,（中位生存期15.00±4.73个月）,F组的15和47个月生存率分别为60.00％和30.00％,中位生存期（47.00±23.83）月,（P=0.2775）:C组的10、24和47个月生存率分别为57.14％、38.10％和0.00％。（中位生存期23.00±14.52月）,显著高于D组的36.10％、7.22％和0.00％,（中位生存期8.00±0.88月）,（P=0.0441）。结论:放疗结合化疗有可能延长“高危”类晚期肺鳞癌患者的生存     

Effects of early intervention with epoetin alfa on transfusion requirement, hemoglobin level and survival during platinum-based chemotherapy: Results of a multicenter randomised controlled trial

This work was conducted to evaluate the effect of early intervention with epoetin alfa (EPO) on transfusion requirements, hemoglobin level (Hb), quality of life (QOL) and to explore a possible relationship between the use of EPO and survival, in patients with solid tumors receiving platinum-based chemotherapy. Three hundred and sixteen patients with Hb12.1g/dL were randomised 2:1 to EPO 10000 IU thrice weekly subcutaneously (n = 211) or best supportive care (BSC) (n = 105). The primary end point was proportion of patients transfused while secondary end points were changes in Hb and QOL. The protocol was amended before the first patient was recruited to also prospectively collect survival data. EPO therapy significantly decreased transfusion requirements (P < 0.001) and increased Hb (P < 0.005). EPO-treated patients had significantly improved QOL compared with BSC patients (P < 0.05). Kaplan-Meier estimates showed no differences in 12-month survival (P = 0.39), despite a significantly greater number of patients with metastatic disease in the EPO group (78% vs. 61%, P = 0.001). EPO was well tolerated. This study has shown that early intervention with EPO can result in a significant reduction of transfusion requirements and increases in Hb and QOL in patients with mild anemia during platinum-based chemotherapy.     

Weekly epoetin alfa maintains hemoglobin, improves quality of life, and reduces transfusion in breast cancer patients receiving chemotherapy.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.     

Early intervention with epoetin alfa during platinum-based chemotherapy: an analysis of the results of a multicenter, randomized, controlled trial based on initial hemoglobin level

OBJECTIVE: This analysis of the results of a randomized, controlled trial evaluating the effects of epoetin alfa (EPO) therapy on transfusion requirements, hemoglobin (Hb), and quality of life (QOL) in patients with cancer receiving platinum-based chemotherapy was conducted to evaluate the effect of initial Hb level on study outcomes. METHODS: Patients with Hb levels < or =12.1 g/dl were randomized 2:1 to receive EPO, 10,000 U three times weekly s.c. or best supportive care (BSC) until 4 weeks after their last chemotherapy cycle. For this analysis, patients were stratified by baseline Hb level (< or =9.7 g/dl, >9.7 g/dl to < or =10.5 g/dl, >10.5 g/dl to < or =11.3 g/dl, and >11.3 g/dl to < or =12.1 g/dl), and study results were reanalyzed. RESULTS: Significantly fewer EPO patients than BSC patients with initial Hb levels >9.7 g/dl to < or =12.1 g/dl required transfusions. EPO maintained Hb levels throughout the study for patients with Hb levels >11.3 g/dl to < or =12.1 g/dl, compared with a decrease with BSC. For patients with baseline Hb levels >10.5 g/dl, for whom the mean changes from baseline to last assessment were measured by the Cancer Linear Analogue Scale assessments of energy and overall QOL as well as by the Functional Assessment of Cancer Therapy (FACT)-Fatigue and FACT-An Anemia subscale, QOL scores were significantly greater with EPO than with BSC. QOL declined in patients receiving BSC, and the mean decreases in QOL scores were greater for BSC patients with baseline Hb levels >10.5 g/dl, compared with the overall BSC group. CONCLUSION: In patients with cancer receiving platinum-based chemotherapy and with baseline Hb levels >10.5 g/dl, early intervention with EPO reduces transfusions, maintains Hb level, and maintains or improves QOL. This study supports the positive effects of early intervention when analyzed according to initial Hb value.     

Randomized, double-blind, placebo-controlled trial of recombinant human erythropoietin, epoetin Beta, in hematologic malignancies.

PURPOSE: To investigate the effect of recombinant human erythropoietin (epoetin beta) on anemia, transfusion need, and quality of life (QOL) in severely anemic patients with low-grade non-Hodgkin's lymphoma (NHL), chronic lymphocytic leukemia (CLL), or multiple myeloma (MM). PATIENTS AND METHODS: Transfusion-dependent patients with NHL (n = 106), CLL (n = 126), or MM (n = 117) and a low serum erythropoietin concentration were randomized to receive epoetin beta 150 IU/kg or placebo subcutaneously three times a week for 16 weeks. Primary efficacy criteria were transfusion-free and transfusion- and severe anemia-free survival (hemoglobin [Hb] > 8.5 g/dL) between weeks 5 to 16. Response was defined as an increase in Hb > or = 2 g/dL with elimination of transfusion need. QOL was assessed by the Functional Assessment of Cancer Therapy scale. RESULTS: Transfusion-free (P =.0012) survival and transfusion- and severe anemia-free survival (P =.0001) were significantly greater in the epoetin beta group versus placebo (Wald chi(2) test), giving a relative risk reduction of 43% and 51%, respectively. The response rate was 67% and 27% in the epoetin beta versus the placebo group, respectively (P <.0001). After 12 and 16 weeks of treatment, QOL significantly improved in the epoetin beta group compared with placebo (P <.05); this improvement correlated with an increase in Hb concentration (> or = 2 g/dL). A target Hb that could be generally recommended could not be identified. CONCLUSION: Many severely anemic and transfusion-dependent patients with advanced MM, NHL, and CLL and a low performance status benefited from epoetin therapy, with elimination of severe anemia and transfusion need, and improvement in QOL.     

Effects of epoetin alfa on hematologic parameters and quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial.

PURPOSE: This randomized, double-blind, placebo-controlled clinical trial assessed the effects of epoetin alfa on transfusion requirements, hematopoietic parameters, quality of life (QOL), and safety in anemic cancer patients receiving nonplatinum chemotherapy. The study also explored a possible relationship between increased hemoglobin and survival. PATIENTS AND METHODS: Three hundred seventy-five patients with solid or nonmyeloid hematologic malignancies and hemoglobin levels < or = 10.5 g/dL, or greater than 10.5 g/dL but < or = 12.0 g/dL after a hemoglobin decrease of > or = 1.5 g/dL per cycle since starting chemotherapy, were randomized 2:1 to epoetin alfa 150 to 300 IU/kg (n = 251) or placebo (n = 124) three times per week subcutaneously for 12 to 24 weeks. The primary end point was proportion of patients transfused; secondary end points were change in hemoglobin and QOL. The protocol was amended before unblinding to prospectively collect and assess survival data 12 months after the last patient completed the study. RESULTS: Epoetin alfa, compared with placebo, significantly decreased transfusion requirements (P =.0057) and increased hemoglobin (P <.001). Improvement of all primary cancer- and anemia-specific QOL domains, including energy level, ability to do daily activities, and fatigue, was significantly (P <.01) greater for epoetin alfa versus placebo patients. Although the study was not powered for survival as an end point, Kaplan-Meier estimates showed a trend in overall survival favoring epoetin alfa (P =.13, log-rank test), and Cox regression analysis showed an estimated hazards ratio of 1.309 (P =.052) favoring epoetin alfa. Adverse events were comparable between groups. CONCLUSION: Epoetin alfa safely and effectively ameliorates anemia and significantly improves QOL in cancer patients receiving nonplatinum chemotherapy. Encouraging results regarding increased survival warrant another trial designed to confirm these findings.     

Randomized comparison of epoetin alfa (40,000 U weekly) and darbepoetin alfa (200 microg every 2 weeks) in anemic patients with cancer receiving chemotherapy

This is the first randomized, open-label, multicenter trial designed and powered to directly compare the hemoglobin (Hb) response to epoetin alfa (EPO), 40,000 U once weekly (QW), with that to darbepoetin alfa (DARB), 200 microg every 2 weeks (Q2W), in anemic patients with cancer receiving chemotherapy (CT). Transfusion requirements, quality of life (QOL), and safety also were evaluated. Adults with solid tumors scheduled to receive CT for > or =12 weeks and with baseline Hb < or =11 g/dl were randomized to receive either EPO 40,000 U QW (n = 178) or DARB 200 microg Q2W (n = 180) s.c. for up to 16 weeks. Doses were increased for nonresponders (Hb increase <1 g/dl) after 4 (EPO) or 6 (DARB) weeks, as per National Comprehensive Cancer Network guidelines, and were reduced for a rapid rise in Hb (>1.3 g/dl [EPO] or >1.0 g/dl [DARB] within any 2-week period) or for an Hb level >13 g/dl. The proportion of patients achieving a > or =1-g/dl Hb rise by week 5, the primary end point, was significantly higher with EPO (47.0%) than with DARB (32.5%), and EPO-treated patients achieved a > or =1-g/dl Hb increase significantly earlier than those receiving DARB (median, 35 days versus 46 days). The mean increase in Hb from baseline was significantly higher at weeks 5, 9, 13, and the end of the study with EPO than with DARB. The number of units transfused per patient was significantly lower for the EPO group than for the DARB group. The proportions of patients requiring transfusions, mean QOL improvements, and tolerability profiles were similar in the two groups.     

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.     

Combined use of erythropoietin and granulocyte colony-stimulating factor does not decrease blood transfusion requirements during induction therapy for high-risk neuroblastoma: a randomized controlled trial.

PURPOSE: To evaluate the efficacy of recombinant erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF) in reducing blood transfusion requirements and stimulating hematopoiesis in children with high-risk neuroblastoma. PATIENTS AND METHODS: Thirty-eight patients given six cycles of intensive induction chemotherapy for high-risk neuroblastoma were randomized to receive G-CSF (n = 20) or G-CSF + EPO (n = 18). Cytokines were given subcutaneously each day, starting 24 hours after each chemotherapy cycle and continuing until 48 hours before the start of the next cycle. The primary end point was the effect of EPO on total red cell transfusion requirements during induction therapy. RESULTS: Patients who received G-CSF + EPO had a higher red cell transfusion requirement (median, 161.0 mL/kg) than did those who received G-CSF alone (median, 106.6 mL/kg; P =.005). In addition, among patients given transfusions for hemoglobin < or = 8 g/dL, those in the G-CSF + EPO group received more red cell transfusions than did those given G-CSF alone (median per patient, 10 v 8, respectively; P =.044). The two treatment groups had similar cumulative durations of neutropenia, incidences of febrile neutropenia, platelet transfusion requirements, and numbers of platelet transfusions; they also received induction chemotherapy for similar durations and had similar probabilities of progression-free survival and overall survival. CONCLUSION: The addition of EPO to the G-CSF regimen provides no benefit for patients receiving intensive induction chemotherapy for high-risk neuroblastoma.     

Standard of care for cancer-related anemia: improving hemoglobin levels and quality of life

The introduction of recombinant human erythropoietin (rHuEPO) has proven to be a major advance in the therapeutic options available for managing anemia in cancer patients. The results of placebo-controlled clinical trials and large, community-based, open-label studies have confirmed that epoetin alfa, a recombinant human erythropoietin, significantly reduces transfusion requirements, and reliably increases hemoglobin (Hb) levels in anemic (Hb level <12 g/dl) cancer patients undergoing chemotherapy. Increased Hb improves patients' energy level and their ability to perform the activities of daily living, as well as their overall quality of life (QOL). These findings are independent of tumor type and disease status and are comparable in patients receiving nonplatinum- and platinum-based chemotherapeutic regimens. Furthermore, more than a decade of use in clinical trials and by physicians in routine clinical practice has demonstrated that epoetin alfa is safe and well tolerated when used to treat cancer patients with anemia. The availability of epoetin alfa as an alternative to transfusion has changed practices in anemia management; physicians can now treat anemia with the goal of achieving adequate Hb levels to relieve anemia-related fatigue, a major symptom contributing to decreased QOL in cancer patients. Incremental benefit analysis has shown that increasing Hb level from 11 g/dl to 12 g/dl yields the greatest improvement in QOL per 1 g/dl increase in Hb. The demonstrated efficacy of epoetin alfa for increasing Hb levels and improving patient QOL have made this agent a rationale choice for management of cancer-related anemia. Ongoing research will continue to provide new insights into best management of anemia with epoetin alfa in cancer patients.     

Phase III, randomized, double-blind study of epoetin alfa compared with placebo in anemic patients receiving chemotherapy.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.