PEG-rhG-CSF预防结肠癌双周剂量密集方案辅助化疗后中性粒细胞减少的临床疗效观察

目的:观察聚乙二醇化重组人粒细胞集落刺激因子（polyethylene glycol recombinant human granulocyte colony stimulating factor，PEG-rhG-CSF）预防结肠癌双周剂量密集方案（FOLFOX6）辅助化疗后中性粒细胞减少的疗效和安全性。方法:收集中国人民解放军北部战区总医院2016年12月至2017年9月间52例接受剂量密集方案辅助化疗的结肠癌患者，治疗组20例化疗后24小时皮下注射6 mg PEG-rhG-CSF，对照组32例化疗后未使PEG-rhG-CSF，患者出院后根据验血结果由经治医师决定是否加用重组人粒细胞集落刺激因子（rhG-CSF）。主要观察患者再次应用rhG-CSF的频次、患者Ⅲ-Ⅳ 度中性粒细胞减少的发生率、患者粒缺性发热的发生率、因粒细胞减少而进行减量或延迟治疗的发生率以及患者生活质量改善情况（C-30量表）。结果:治疗组患者无需再次注射rhG-CSF，而对照组患者26例需加用rhG-CSF，并且对照组8例发生Ⅲ-Ⅳ度中性粒细胞减少、2例发生粒缺性发热、4例和7例分别因粒细胞减少而减量和延迟治疗。治疗组患者生理状况、社会/家庭状况和总评分显著高于对照组患者。两组患者不良反应发生率相当，无统计学差异。结论:应用PEG-rhG-CSF可有效预防结肠癌剂量密集方案辅助化疗后Ⅲ-Ⅳ度中性粒细胞减少的发生，减少因上述不良反应而延迟化疗的发生，化疗间歇期患者无需再次应用rhG-CSF治疗，同时提高患者生活质量。PEG-rhG-CSF安全性高，无明显不良反应。     

聚乙二醇化重组人粒细胞集落刺激因子预防化疗后中性粒细胞减少的有效性分析*

目的:比较每周期1 剂聚乙二醇化重组人粒细胞集落刺激因子（PEG-rhG-CSF）与每日1 剂重组人粒细胞集落刺激因子（rhG-CSF ）预防癌症患者化疗后中性粒细胞减少的有效性。方法:合并分析PEG-rhG-CSF的2 期和3 期临床研究中的单中心数据,比较疗效与安全性指标。两项研究均为随机、自身交叉对照试验。56例初治恶性肿瘤患者接受2 个周期常用化疗方案治疗,且化疗方案相同,其中试验周期给予PEG-rhG-CSF100 μ g/kg 皮下注射,每个周期1 次;对照周期皮下注射rhG-CSF 5 μ g/kg ,每日1 次。结果:2 个研究单中心共纳入56例患者,其中53例可进行疗效评价,PEG-rhG-CSF和rhG-CSF 各使用53个周期。在使用PEG-rhG-CSF的周期和使用rhG-CSF 的周期中,4 度外周血中性粒细胞绝对值（ANC ）减少未发生率均为94.3%（50/ 53）,均未出现中性粒细胞减少性发热,抗生素使用率分别为7.5%（4/ 53）和3.8%（2/ 53,P = 0.678）。 全组患者中位应用rhG-CSF 天数为10（3～14）天。此两种药物的不良反应均为骨痛、注射部位疼痛、心悸、发热和乏力等。结论:1 剂聚乙二醇化重组人粒细胞集落刺激因子预防化疗后中性粒细胞减少的有效性与连续10剂常规重组人粒细胞集落刺激因子相似。      

低剂量格拉诺赛特(rtG-CSF)防治卵巢癌化疗后白细胞减少症的疗效观察

目的:探讨低剂量格拉诺赛特(rhG-CSF)的不同用法对卵巢癌化疗后白细胞和中性粒细胞减少的防治作用。方法:43例的上皮性卵巢癌化疗患者随机分为3组,其中,A组(共66疗程)不用rhG-CSF;B组(共57疗程)为白细胞计数<2.0×109/L时给予rhG-CSF,C组(共73疗程)自化疗结束后48小时起给予rhG-CSF,剂量均为50μg/日,皮下注射。结果:C组白细胞最低值的持续时间明显短于A和B组,分别为白细胞计数10日;中性粒细胞计数11日(P<0.01),平均最低值分别为3.01×109/L和0.986×109/L。B和C组rhG-CSF的作用并不随年龄、体重和化疗次数而改变。结论:rhG-CSF可以维持白细胞和中性粒细胞的水平,早期应用G-CSF可能会增大化疗剂量或缩短化疗间歇时间,从而提高化疗强度。     

重组人粒细胞集落刺激因子治疗10例恶性肿瘤化疗所致的Ⅳ度白细胞减少症

目的研究基因重组人粒细胞集落刺激因子(rhG-CSF,惠尔血)对化疗所致的白细胞减少症的疗效.方法用rhG-CSF治疗10例恶性肿瘤化疗所致Ⅳ度白细胞减少症.白细胞小于1.9×109/L或中性粒细胞绝对计数(ANC)小于0.9×109/L时开始用rhG-CSF150μg,皮下注射,每日1次,等白细胞回升5.0×109/L以上或ANC大于2.5×109/L时停药.结果rhG-CSF能使化疗后Ⅳ度白细胞减少症患者的白细胞回升至正常范围,平均时间为6.8天,感染发生率为60%(6/10).结论rhG-CSF可有效治疗化疗所致的Ⅳ度白细胞减少症,减少感染机会,有利于化疗顺利进行.     

小剂量rhG-CSF在急性淋巴细胞白血病化疗中的应用

本研究报告基因重组人类粒细胞集落刺激因子(rhG-CSF）应用于急性淋巴细胞白血病(ALL）患者化疗后对其外周血白细胞及中性粒细胞的影响．同时观察化疗后感染及药物不良反应的发生情况。     

聚乙二醇化重组人粒细胞集落刺激因子预防化疗后中性粒细胞减少症临床疗效观察中性粒细胞减少症临床疗效观察

比较聚乙二醇化重组人粒细胞集落刺激因子（PEG-rhG-CSF）和重组人粒细胞集落刺激因子（rhG-CSF）预防化疗后中性粒细胞减少症的有效性和安全性。方法:采用随机自身交叉对照,选择初治恶性肿瘤患者接受2个周期相同方案的化疗,其中试验周期给予PEG-rhG-CSF 100 μg/kg皮下注射一次,对照周期每日一次皮下注射rhG-CSF 5 μg/kg,直至外周血中性粒细胞绝对值（ANC）在低谷后连续两次检查≥5.0×109/L。结果:入组78例患者,在76个试验周期和74个对照周期中,ANC<1.5×109/L的发生率分别为30.26%和21.16%,持续时间分别为2.34 d和2.31 d;ANC<0.5×109/L的发生率分别为3.8%和3.0%;抗生素使用率分别为11.59%和9.60%（P均<0.05）。试验药和对照药的不良反应均为骨骼肌肉疼痛、乏力、发热、头晕等,发生率与严重程度相似。结论:PEG-rhG-CSF一次给药的疗效和不良反应与rhG-CSF多次给药相似。      

聚乙二醇化重组人粒细胞集落刺激因子预防化疗后中性粒细胞减少症临床疗效观察

目的:比较聚乙二醇化重组人粒细胞集落刺激因子 (PEG-rhG-CSF) 和重组人粒细胞集落刺激因子 (rhG-CSF) 预防化疗后中性粒细胞减少症的有效性和安全性.方法:采用随机自身交叉对照,选择初治恶性肿瘤患者接受2个周期相同方案的化疗,其中试验周期给予PEG-rhG-CSF 100 μg/kg皮下注射一次,对照周期每日一次皮下注射rhG-CSF 5 μg/kg,直至外周血中性粒细胞绝对值 (ANC) 在低谷后连续两次检查≥5.0×109/L.结果:入组78例患者,在76个试验周期和74个对照周期中,ANC<1.5×109/L的发生率分别为30.26%和21.16%,持续时间分别为2.34 d和2.31 d; ANC<0.5×109/L的发生率分别为3.8%和3.0%; 抗生素使用率分别为11.59%和9.60% (P均<0.05).试验药和对照药的不良反应均为骨骼肌肉疼痛、乏力、发热、头晕等,发生率与严重程度相似.结论:PEG-rhG-CSF一次给药的疗效和不良反应与rhG-CSF多次给药相似.     

重组人粒细胞集落刺激因子预防乳腺癌化疗后骨髓抑制的疗效分析

背景与目的：骨髓抑制是化疗最严重的不良反应,以中性粒细胞减少最常见。重组人粒细胞集落刺激因子(recombinant human granulocyte colony-stimulating factor,rhG-CSF)能诱导造血祖细胞向中性粒细胞分化,并调节中性粒细胞的功能活性,可用于肿瘤化疗后严重的中性粒细胞缺乏症,以保证原计划化疗方案的完成。本文旨在了解应用rhG-CSF治疗乳腺癌化疗后骨髓抑制的疗效以及预防性作用。方法：采用回顾性调查方法,筛选出在天津医科大学肿瘤医院进行多西紫杉醇(docetaxel)75 mg/m²、表柔比星(epirubicin) 65 mg/m²与环磷酰胺(cyclophosphamide)500 mg/m²(TEC)化疗方案的浸润性乳腺癌患者,在第1个周期末次给药后24~48 h内给予rhG-CSF为预防组,以24~48 h内未给予rhG-CSF为对照组,评估2组化疗后骨髓抑制的发生情况以及用药的安全性。结果：在预防组60例患者中,外周血白细胞(white blood cell,WBC)＜4.0×10⁹/L的发生率为25.0%,中性粒细胞绝对数(absolute neutrophil count,ANC)＜2.0×10⁹/L的发生率为23.3%;在对照组60例患者中,WBC＜4.0×10⁹/L的发生率为78.3%,ANC＜2.0×10⁹/L的发生率为73.3%,差异有统计学意义(P＜0.01)。2组的化疗延迟率分别为5.0%和25.0%(P=0.002),化疗延迟时间分别为(2.33±0.58)d和(3.73±0.80)d(P=0.011),差异均有统计学意义。预防组发热性中性粒细胞减少症(febrile neutropenia,FN)的发生率为1.7%,对照组FN的发生率为20%,预防组明显低于对照组(P=0.001)。2组对血红蛋白(hemoglobin,Hb)与血小板(platelets,PLT)水平均无显著影响(P=0.547;P=0.285)。预防组rhG-CSF用药后不良反应的发生率为8.3%,而对照组为21.6%,差异有统计学意义(P=0.041)。结论：对于浸润性乳腺癌患者,在第一周期化疗后24~48 h内预防性给予rhG-CSF,能降低白细胞减少症的发生,减轻骨髓抑制的程度及持续时间,降低FN的发生风险,并且能减少rhG-CSF用药不良反应的发生。     

G—CSF治疗化疗引起白细胞减少症三种方法的成本／效果分析

目的：确定标准剂量化疗后重组人粒细胞集落刺激因子（rhG-CSF)合理的用药方法。方法：采用前瞻性自身对照方法，分别以不同顺序进行3个疗程化疗加rhG-CSF治疗，A周期为化疗后预防性应用rhG-CSF,B周期为化疗后出现Ⅳ度白细胞下降，再予rhG-CSF治疗，C周期为出现Ⅱ度白细胞下降后加用rhG-CSF治疗，用药物经济学成本/效果分析方法，对其疗效及成本进行评价。结果：化疗后预防性应用rhG-CSF和Ⅱ度白细胞下降后rhG-CSF，与Ⅳ度白细胞下降后应用rhG-CSF相比，疗效均明显提高，分别为76%，80%，46%，前二者之间疗效差异无显著性，前者疗效每提高1%，成本增加5514元，后者疗效每提高1%，成本增加1391元。结论：标准剂量化疗，出现Ⅱ度白细胞下降后应用rhG-CSF，最有效，经济，合理。     

化疗前应用重组人粒细胞集落刺激因子预防白细胞减少

 【摘要】　目的　观察重组人粒细胞集落刺激因子（rhG-CSF）预防化疗后中性粒细胞减少症的有效性和安全性。方法　采用随机对照方法，初治恶性肿瘤患者接受1个周期的化疗，其中治疗组化疗前24 h给予rhG-CSF 150 μg皮下注射1次，对照组不给予rhG-CSF。结果　入组52例肿瘤患者，分为治疗组和对照组各26例，WBC＜4.0×109／L的发生率分别为19.23 %和53.85 %（P＜0.05），白细胞减少发生率Ⅰ度分别为7.69 %和19.23 %，Ⅱ度7.69 %和15.39 %，Ⅲ度3.85 %和1.54 %，Ⅳ度0和7.69 %； 持续时间分别为1.27 d和4.04 d（P＜0.05）；抗生素使用率分别为7.69 %和26.92 %（P＜0.05）；发热性中性粒细胞减少发生率分别为3.85 %和26.92 %（P＜0.05）。rhG-CSF的毒副作用主要为骨骼肌肉疼痛、乏力、头晕等。结论　化疗前应用rhG-CSF能有效控制肿瘤化疗后白细胞减少的发生，降低肿瘤化疗后白细胞减少的程度。     

The impact of Filgrastim schedule variation on hematopoietic recovery post-chemotherapy

Background: A phase 2 trial was done to study effects of varying treatment schedule of Filgrastim (r-metHuG-CSF) on hematologic recovery following chemotherapy.Patients and methods: Forty-six patients with extensive small-cell carcinoma of the lung were randomized to receive one of three Filgrastim schedules following cyclophosphamide, doxorubicin, and etoposide (CAE) chemotherapy for up to six cycles of treatment. Chemotherapy was delivered on days 1–3 of each 21-day cycle with Filgrastim initiated at 5 µg/kg/day subcutaneously (SC) beginning on day 4, day 6, or day 8 and continuing until post-nadir neutrophil recovery.Results: During the first cycle of chemotherapy, the duration of neutropenia was similar for all three schedules; however, the pattern of absolute neutrophil count (ANC) recovery differed. In subsequent cycles of treatment, an improvement in the severity of neutropenia occurred in patients on the day-4 and day-6 schedules compared with the first cycle of chemotherapy. By contrast, patients on the day-8 schedule continued to experience neutropenia similar to that seen in cycle one. Patients on the day-8 schedule also experienced a greater magnitude of grade IV thrombocytopenia in later cycles of treatment.Conclusion: Timing of Filgrastim administration post-chemotherapy has profound effects on hematologic recovery. Delay of Filgrastim until day 8 was associated with suboptimal hematologic recovery compared with administration of Filgrastim on day 4 or day 6. Initiation of Filgrastim on day 4 or day 6 showed a similar pattern of hematologic recovery. Beginning Filgrastim on day 6 is associated with a decrease in the total dose of Filgrastim administered.     

Effects of the in vivo Administration of Recombinant Human Granulocyte Colony-stimulating Factor Following Cytotoxic Chemotherapy on Granulocytic Precursors in Patients with Malignant Lymphoma1

We examined the effects of the in vivo administration of recombinant granulocytc colony-stimulating factor (rhG-CSF) on granulocytic precursors in the bone marrow of 4 patients with malignant lymphoma who received chemotherapy. Patients were treated with rhG-CSF at doses of 100–800 μg/ m²/day intravenously for 14 days only in the first course of chemotherapy (G-CSF course) followed by the second course of chemotherapy without rhG-CSF which was used as a control course. In the G-CSF course, white blood cell counts (WBCs) demonstrated a biphasic response consisting of a first peak observed within a few days after the initiation of rhG-CSF administration, and a second peak observed on the last day of rhG-CSF injection or the day after. In the second peak, the incidence of granulocyte-macrophage colony-forming units (CFU-GM) in mononucleated bone marrow cells did not change significantly after treatment with rhG-CSF as compared with a control. However, since the number of nucleated cells in the bone marrow increased, the absolute number of CFU-GM in the bone marrow increased. The number of mature and immature granulocytes in the bone marrow increased. These findings suggest that G-CSF stimulates the proliferation and differentiation of granulocytic precursors in the bone marrow in granulocytopenic patients who received cytotoxic drugs and causes mature granulocytes to be released from the bone marrow.     

Effects of the in vivo administration of recombinant human granulocyte colony-stimulating factor following cytotoxic chemotherapy on granulocytic precursors in patients with malignant lymphoma

We examined the effects of the in vivo administration of recombinant granulocyte colony-stimulating factor (rhG-CSF) on granulocytic precursors in the bone marrow of 4 patients with malignant lymphoma who received chemotherapy. Patients were treated with rhG-CSF at doses of 100-800 micrograms/m2/day intravenously for 14 days only in the first course of chemotherapy (G-CSF course) followed by the second course of chemotherapy without rhG-CSF which was used as a control course. In the G-CSF course, white blood cell counts (WBCs) demonstrated a biphasic response consisting of a first peak observed within a few days after the initiation of rhG-CSF administration, and a second peak observed on the last day of rhG-CSF injection or the day after. In the second peak, the incidence of granulocyte-macrophage colony-forming units (CFU-GM) in mononucleated bone marrow cells did not change significantly after treatment with rhG-CSF as compared with a control. However, since the number of nucleated cells in the bone marrow increased, the absolute number of CFU-GM in the bone marrow increased. The number of mature and immature granulocytes in the bone marrow increased. These findings suggest that G-CSF stimulates the proliferation and differentiation of granulocytic precursors in the bone marrow in granulocytopenic patients who received cytotoxic drugs and causes mature granulocytes to be released from the bone marrow.     

A combined analysis of two pivotal randomized trials of a single dose of pegfilgrastim per chemotherapy cycle and daily Filgrastim in patients with stage II-IV breast cancer

This combined, retrospective analysis compared once-per-chemotherapy-cycle pegfilgrastim with daily Filgrastim in breast cancer patients undergoing myelosuppressive chemotherapy enrolled in two similarly designed, randomized, double-blind, pivotal trials. On day 2 of each chemotherapy cycle, a single subcutaneous (SC) injection of pegfilgrastim [either 6 mg (n=77) or 100 microg/kg (n=149)] was administered, or daily Filgrastim SC injections (5 microg/kg/day; n=222) were initiated and continued until either absolute neutrophil count (ANC) > or =10 x 10(9)/l after the expected nadir or for up to 14 days, whichever occurred first. Individually, each of these trials demonstrated that a single pegfilgrastim injection per cycle is as effective at reducing the duration of severe neutropenia as daily injections of Filgrastim. Clinical efficacy data from the two trials were combined for analysis (n=448). The risk of febrile neutropenia (FN; absolute neutrophil count <0.5 x 10(9)/l with fever > or =38.2 degrees C) was significantly lower [11% vs 19%, respectively; relative risk = 0.56 (95% confidence interval: 0.35, 0.89)] in patients receiving pegfilgrastim than for those receiving Filgrastim. Trends towards lower risks of hospitalization and intravenous anti-infective use were also observed. These observations were consistent irrespective of risk factors, including age, disease stage, performance status and prior treatment. Pegfilgrastim may offer patients more effective protection against neutropenic complications of chemotherapy with fewer injections and less disruption to their lives.     

注射用聚乙二醇化重组人粒细胞集落刺激因子Ⅰ期临床耐受性试验

背景与目的：重组人粒细胞集落刺激因子（rhG—CSF）是防治肿瘤化放疗引起的中性粒细胞减少症的有效药物,但半衰期短,需每日给药。聚乙二醇化重组人粒细胞集落刺激因子（PEG-rhG-CSF）是将聚乙二醇与rhG—CSF结合而成的长效制剂,与常规rhG—CSF相比,能减少给药次数,避免患者反复接受注射的痛苦。本研究旨在评价PEG-rhG-CSF用于国人的安全性和耐受性,初步观察化疗后PEG—rhG—CSF升高外周血中性粒细胞和CD34^＋细胞的效果。方法：本研究为开放性试验,经病理组织学或细胞学确诊的初治非小细胞肺癌和乳腺癌患者进入本研究,受试者接受两个周期相同方案的化疗,第一周期为对照周期,第二周期在化疗药物给药结束后48h给予PEG-rhG-CSF。PEG-rhG-CSF的初始剂量为30μg／kg,递增剂量依次为60μg／kg、100μg／kg和200μg／kg,每一剂量组4例受试患者。结果：入组16例患者均可评价疗效和安全性。与PEG-rhG-CSF相关的不良反应主要有骨关节或肌肉疼痛（13／16）、疲乏（10／16）、头晕（2／16）,1例受试患者出现注射部位轻度疼痛,自行缓解。与对照周期相比,使用PEG-rhG-CSF后中性粒细胞绝对值（ANC）最低值的出现时间前移,ANC最低值提高。ANC的变化呈现一定程度的量效关系,60、100和200μg／kg剂量组均能较好地防治化疗后的中性粒细胞减少症．且维持时间较长,并能够增高外周血CD34^＋细胞的数量。未出现PEG-rhG-CSF的剂量限制性毒性,也未达到最大耐受剂量。结论：PEG-rhG-CSF显示了良好的耐受性．未出现严重不良事件。由于100μg／kg剂量组的不良反应轻于200μg／kg剂量组,疗效已能满足临床需要,因此推荐Ⅱ期临床试验的剂量为100μg／kg。     

吉粒芬治疗化疗所致粒细胞减少的临床研究

 目的　研究低剂量、短期使用吉粒芬治疗化疗所致粒细胞减少的临床疗效。方法　108例患者随机分A、B、C3组。A组吉粒芬75μg/qd×3d;B组吉粒芬75μg/qod×6d;C组吉粒芬75μg/qd×5d。均为皮下注射。结果　低剂量、短期使用吉粒芬在粒细胞降至1500×109/L以上时有效,副作用少,能使患者安然度过粒细胞下降易感染期,以B组隔日使用疗效最好。结论　低剂量、短期使用吉粒芬可在粒细胞未降至1500×109/L以上时使用有效,量不变隔日用效果更好。     

低剂量格拉诺赛特（rhG－CSF）防治肺癌CE方案化疗后中性粒细胞减少症的临床研究

作者采用随机分组、自身交叉对比的方法，观察了低剂量格拉诺赛特（Ｇｒａｎｏｃｙｔｅ，ｒｈＧ－ＣＳＦ）对２２例肺癌ＣＥ方案（卡铂＋足叶乙甙）化疗后白细胞和中性粒细胞减少症的防治作用及毒副反应。患者随机分成Ａ、Ｂ两组（各１１例）。Ａ组第一周期化疗后加用格拉诺赛特，第二周期单用化疗；Ｂ组第一周期单用化疗，第二周期化疗后加用格拉诺赛特。格拉诺赛特在化疗药物未次给药后４８ｈ起，５０μｇ１次／日皮下注射。结果表明，该剂量的格拉诺赛特可以明显减轻化疗过程中白细胞和中性粒细胞下降的程度，降低中性粒细胞严重降低的发生率，缩短其在正常值以下的持续时间，促进早日恢复，缩短化疗周期的间隔时间，使化疗可以如期进行。低剂量的格拉诺赛特疗效确切，副反应轻微。     

Clinical effect of recombinant human G-CSF on neutropenia induced by chemotherapy for lung cancer. rG.CSF Cooperation Study Group]

The therapeutic evaluation of rG.CSF has been studied on neutropenic patients receiving lung cancer chemotherapy with focusing the change in the absolute neutrophil counting (ANC) in the patients during chemotherapy and subsequent rG.CSF treatment by daily dosing either at 0.4, 2.0, 5.0 and 10.0 micrograms/kg intravenously or at 2.0 and 5.0 micrograms/kg subcutaneously. The daily rG.CSF dosing for 14 consecutive days was performed on the patients upon completion of the 28-day chemotherapy for lung cancer. As a result, remarkable recovery of ANC was observed in the patients administered at doses of more than 5 and 2.0 micrograms/kg intravenously and subcutaneously, respectively. Additionally, the shortening of the neutropenia (ANC: below 1,000/cmm) was observed in the patients at doses of not less than 2.0 micrograms/kg in both administration routes. In conclusion, rG.CSF treatment demonstrates the completion and/or shortening of the chemotherapy cycle for lung cancer at a subcutaneous dose of 2.0 micrograms/kg and at a intravenous dose of 5.0 micrograms/kg. No adverse drug effects were observed in all patients during the study.     

Dose density in adjuvant chemotherapy for breast cancer

BACKGROUND: Dose-dense chemotherapy increases the dose intensity of the regimen by delivering standard-dose chemotherapy with shorter intervals between the cycles. This article discusses the rationale for dose-dense therapy and reviews the results with dose-dense adjuvant regimens in recent clinical trials in breast cancer. METHODS: The papers for this review covered evidence of a dose-response relation in cancer chemotherapy; the rationale for dose-intense (and specifically dose-dense) therapy; and clinical experience with dose-dense regimens in adjuvant chemotherapy for breast cancer, with particular attention to outcomes and toxicity. RESULTS: Evidence supports maintaining the dose intensity of adjuvant chemotherapy within the conventional dose range. Disease-free and overall survival with combination cyclophosphamide, methotrexate, and fluorouracil are significantly improved when patients receive within 85% of the planned dose. Moderate and high dose cyclophosphamide, doxorubicin, and fluorouracil within the standard range results in greater disease-free and overall survival than the low dose regimen. The sequential addition of paclitaxel after concurrent doxorubicin and cyclophosphamide also significantly improves survival. Disease-free and overall survival with dose-dense sequential or concurrent doxorubicin, cyclophosphamide, and paclitaxel with filgrastim (rhG-CSF; NEUPOGEN) support are significantly greater than with conventional schedules (q21d). CONCLUSIONS: The delivered dose intensity of adjuvant chemotherapy within the standard dose range is an important predictor of the clinical outcome. Prospective trials of high-dose chemotherapy have shown no improvement over standard regimens, and toxicity was greater. Dose-dense adjuvant chemotherapy improves the clinical outcomes with doxorubicin-containing regimens. Filgrastim support enables the delivery of dose-dense chemotherapy and reduces the risk of neutropenia and its complications.