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…

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对２２例肺癌ＣＥ方案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。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组第五周期单用化疗，第二周期化疗后加用格拉诺赛特。     

低剂量格拉诺赛特(rhG-CSF)防治淋巴瘤化疗后白细胞减少症的疗效观察

探讨低剂量格拉诺赛特（ｒｈＧ－ＣＳＦ）对淋巴瘤ＣＨＯＰＥ化疗后白细胞和中性粒细胞减少的防治作用。采用随机分组、自身交叉对比的方法。患者随机分为Ａ、Ｂ两组，Ａ组第一周期化疗后加ｒｈＧ－ＣＳＦ，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ｒｈＧ－ＣＳＦ。ｒｈＧ－ＣＳＦ在化疗药物末次给药后４８ｈ起，５０μｇ／日，皮下注射。结果表明，该剂量的ｒｈＧ－ＣＳＦ可以明显减轻化疗过程中的白细胞和中性粒细胞下降的程度，降低感染率，使化疗可以如期进行。低剂量的ｒｈＧ－ＣＳＦ疗效确切，副反应轻微，值得推广。     

低剂量格拉诺赛特（rhG—CSF）防治淋巴瘤化疗后白细胞减少症的 …

探讨低剂量格拉诺赛特（ｒｈＧ－ＣＳＦ）对淋巴瘤ＣＨＯＰＥ化疗后白细胞和中性细胞减少的防治作用，采用随机分组，自身交叉对比的方法，患者随机分为Ａ，Ｂ两组，Ａ组第一周期化疗后加ｒｈＧ－ＣＳＦ，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ｒｈＧ－ＣＳＦ，ｒｈＧ－ＣＳＦ在化疗药物末次给药后４８ｈ起，５０μｇ／日，皮下注射，结果表明，该剂量的ｒｈＧ－ＣＳＦ可以明显减轻化疗过程中的白细胞和中性粒细     

基因重组人粒细胞集落刺激因子防治CHOP和CAF方案化疗所致白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，观察了基因重组人粒细胞集落刺激因子（ＲｅｃｏｍｂｉｎａｎｔＨｕｍａｎＧｒａｎｕｌｏｃｙｔｅＣｏｌｏｎｙ－ＳｔｉｍｕｌａｔｉｎｇＦａｃｔｏｒ，ｒｈＧ－ＣＳＦ，以下简称ｒｈＧ－ＣＳＦ）对２３例肿瘤患者ＣＨＯＰ和ＣＡＦ方案化疗所致白细胞和中性粒细胞减少的防治作用及毒副反应。结果表明，ｒｈＧ－ＣＳＦ可以减轻化疗过程中白细胞和中性粒细胞下降的程度，缩短白细胞和中性粒细胞降至正常值以下的持续时间，促进其早日恢复，使化疗可以如期进行。ｒｈＧ－ＣＳＦ副反应轻微，安全可靠。     

国产rhG—CSF（洁欣）治疗血液肿瘤患者化疗后粒细胞减少的疗效观察

利用基因工程技术生产的重组人粒细胞集落刺激因子(recombinant human gramulocyte colony stimulating factor,rhG-CSF)是一种重要的细胞因子,已广应用于临床,证明它能缩短肿瘤化疗后所致的骨髓抑制,相应地减少由此引起的严重感染的发生率.本组研究的目的是进一步考察苏州中凯生物药业有限公司研制的rhG-CSF(商品名:洁欣)治疗血液系统恶性肿瘤化疗所致粒细胞减少症的治疗效果,并同时与进口同类产品进行比较.本研究由上海9家医疗单位组成临床协作组,从2000年8月至10月对洁欣进行了多中心开放式对照观察,现将结果报告如下.     

国产rhG-CSF预防乳腺癌化疗后中性粒细胞减少症的应用策略

目的:探讨国产重组人粒细胞集落刺激因子(rhG-CSF)预防乳腺癌术后辅助化疗后中性粒细胞减少症的应用策略。方法:选择乳腺癌术后辅助化疗、第1个周期中曾出现4度中性粒细胞减少者32例,化疗方案为AC、FEC100和EC方案。采用3种预防应用rhG-CSF的方法:皮下注射300μg/d,方法1为化疗后第2~15天注射;方法2为第3~10天注射;方法3为第6~13天注射。32例患者随机分成两组,分别为1~3比较组和2~3比较组,在化疗的第2、3个周期采用自身交叉对照法进行比较。结果:方法1的中性粒细胞绝对数(ANC)化疗后无明显下降,在第16~18天时出现高峰。方法2的ANC化疗后出现短暂上升,第10~12天最高,之后下降较明显。方法3的ANC变化较平稳,无明显下降也无明显高峰;方法1和方法3的平均ANC最低值、ANC<2·0×109L-1持续天数及ANC减少症发生率均相似,方法2的平均ANC最低值明显低于方法3,P=0·033;方法1的骨骼肌肉疼痛和注射局部硬结的发生率明显高于方法3,P=0·023和0·029。结论:3种方法总体上均显示了预防化疗后ANC减少的作用,方法3疗效好且不增加不良反应发生率,相对于其他两种方法而言,是一种更好的预防用药策略。     

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。     

粒细胞集落刺激因子治疗肿瘤患者化疗后白细胞减少

我们应用基因重组人粒细胞集落刺激因子(rhG—CSF),治疗32例恶性肿瘤患者化疗后白细胞减少。应用剂量:75ug,每日一次,皮下注射,3～7天。结果:治疗前白细胞最低值(2.40±0.82)G/L,治疗后白细胞值为(4.1±0.36)G/L,两组比较有非常显著性差异(p<0.01)。72％患者用药3天内白细胞由最低恢复至4.0G/L。平均回升时间为3.5天。     

格拉诺赛特对恶性肿瘤大剂量化疗引起的中性粒细胞减少的恢复作用（附35例临床报告）

３５例经病理证实的恶性肿瘤，包括肺癌、恶性淋巴瘤、乳腺癌、脑恶性胶质瘤分别应用不同方案大剂量联合化疗，在第１周期白细胞下降至４×１０９／Ｌ以下者为对照，第二周期原方案化疗并给予格拉诺赛特（Ｇ—ＣＳＦ）。结果证实，格拉诺赛特可提高患者中性粒细胞水平，促性中性粒细胞的恢复，副作用低，是保驾大剂量化疗顺利实施的有价值的辅助药物。     

Subcutaneous Administration of Recombinant Human Granulocyte Colony-stimulating Factor (KRN8601) in Intensive Chemotherapy for Patients with Advanced Lung Cancer

The efficacy and toxicity of recombinant human granulocyte colony-stimulating factor (rh G-CSF, KRN8601) given subcutaneously was evaluated in patients with advanced lung cancer undergoing intensive chemotherapy. Twenty-nine and 30 patients with or without prior therapy were enrolled in this study. At dose levels of 50, 90 and 130 μg/m² of rh G-CSF for 14 consecutive days after chemotherapy, the mean neutrophil nadir counts, the mean neutrophil nadir ratios and the duration of neutropenia (days of < 1000/mm³) were significantly improved. No significant differences were seen in frequency and duration of febrile episodes (>38°C). When rh G-CSF is given subcutaneously, the dose required for an equal effect in alleviating neutropenia is 50% of that required when it is given intravenously. The monocyte counts in the peripheral blood were also significantly increased after chemotherapy cycles with rh G-CSF. The cumulative plasma concentration of rh G-CSF showed a decrement after 7–9 days despite maintenance of the same dose of rh G-CSF for the entire 14 days. In conclusion, 50–130 μg/m² of sc rh G-CSF increased the neutrophil nadir count and shortened the duration of neutropenia in patients undergoing intensive chemotherapy for lung cancer without intolerable side effects.     

惠尔血治疗肺癌化疗所致的白细胞减少的疗效观察

目的：观察麒麟啤酒株式会社生产的基因重组人粒细胞集落刺激因子—惠尔血治疗化疗所致白细胞减少的疗效。方法：用惠尔血治疗３０ 例肺癌化疗所致的白细胞减少与用一般升白细胞中药治疗３４ 例肺癌化疗所致的白细胞减少进行了对比观察。结果：１）一般升白细胞中药和惠尔血均能使化疗后白细胞下降的患者恢复至正常范围（４×１０９／Ｌ） ,但惠尔血组白细胞回升至正常范围的时间平均４．３ 天,而一般升白细胞中药则需１０．３ 天。两组相比,差异有显著性。结论：惠尔血可明显缩短白细胞降至正常值以下的持续时间,有利于化疗的顺利进行。２） 白细胞降至Ⅲ度～Ⅳ度的患者,用惠尔血治疗比一般升白细胞中药恢复正常所用的时间短,故为争取化疗时间,在Ⅲ度～Ⅳ度白细胞下降的患者最好用粒细胞集落刺激因子—惠尔血治疗。     

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。     

rhG-CSF治疗30例肺癌化疗所致的白细胞减少症疗效观察

目的 :观察基因重组人粒细胞集落刺激因子 (rhG CSF ,特尔津 )对肺癌化疗所致的白细胞减少症的疗效。方法 :用rhG CSF治疗 3 0例肺癌化疗所致的白细胞减少患者 ,随机与用其他口服升白细胞药物治疗 3 0例肺癌化疗所致的白细胞减少患者 ,进行对比观察。结果 :rhG CSF和其他口服升白细胞药均能使化疗后白细胞减少症患者的白细胞数恢复至正常范围 ( 4× 10 9/L) ,但rhG -CSF组白细胞数回升至正常的时间比其他口服升白细胞药物组明显缩短 (P <0 0 0 2 ) ,且其继发性感染发生率明显降低 (P =0 0 2 99)。结论 :rhG CSF可有效治疗化疗所致的白细胞减少症 ,并能减少继发性感染机会 ,有利于化疗顺利完成     

吡柔比星为主方案治疗晚期乳腺癌517例的临床研究

对以ＴＨＰ及ＡＤＭ为主联合化疗治疗晚期乳腺癌疗效、毒性反应对比研究。方法：采用随机方法分析Ａ、Ｂ两组，Ａ组（ＴＨＰ组）３５７例，Ｂ组（ＡＤＭ组）１６０例。结果：Ａ组有效率达６３％，Ｂ组有效率５９．４％，Ａ组疗效略有增高，但两组之间无统计学差异，但Ａ组胃肠道反应，脱发，心脏毒性，明显低于Ｂ组。结论以ＴＨＰ为主联合方案治疗晚期乳腺，疗效高，毒性低，使用方便，价格适中，值得临床广泛推广应用。     

Macrophage Colony-stimulating Factor (M-CSF) Prevents Infectious Death Induced by Chemotherapy in Mice, While Granulocyte-CSF Does Not

To clarify the effect of granulocyte colony-stimulating factor (G-CSF) and macrophage colony-stimulating factor (M-CSF/CSF-1) on chemotherapy-induced infection, we estimated the effect of those CSFs on a mouse model under severe myelosuppression. First, we established an animal model in which 48.9% (22/45) of C3H/Hej mice died of sepsis related to severe myelosuppression after intraperitoneal administration of a single dose (9 mg/kg) of mitomycin C (MMC). G-CSF or M-CSF was administered to this model on various administration schedules after chemotherapy, and the effect of those CSFs on survival rates, peripheral blood granulocyte counts, expression of adhesion molecules (CD11a, CD11b, CD18) on granulocytes and granulocyte function (phagocytosis and superoxide anion production) were examined. In all G-CSF administration groups, peripheral blood granulocyte counts were increased, but improvements in expression of adhesion molecules such as CD11a and CD18, and granulocyte function were less marked and survival rates were not unproved. Meanwhile, when M-CSF was administered from 1 to 7 days after chemotherapy, granulocyte and platelet counts were increased, and moreover, expression of adhesion molecules and granulocyte function were markedly improved. Furthermore, the survival rate was significantly improved to 77.8% (28/36) compared with the MMC group ( P <0.05). Positive rate of blood culture examination at 7 days after chemotherapy in the M group was 0%, and was significantly lower than that in the G group (40%) and the MMC group (40%) ( P <0.05). These results demonstrated that it is important not only to increase the granulocyte counts, but also to improve granulocyte functions for preventing infection under myelosuppression after chemotherapy.     

Effect of Granulocyte-Macrophage Colony-Stimulating Factor on Chemotherapy-Related Neutropenia in Patients with Non-Hodgkin's Lymphomas—A Phase I/II Study of Dose and Mode of Administration

The effect of mammalian glycosylated recombinant granulocyte-macrophage colony-stimulating factor was investigated in 24 patients with newly diagnosed non-Hodgkin's lymphoma in a phase I/II study. All patients received standard chemotherapy with CHOP. RhGM-CSF was administered after the first cycle for 5 days, and at one of four dose levels (2, 4, 8 and 16 μg/kg). Patients were randomized to receive the drug either by continuous intravenous infusion or twice daily as subcutaneous injection.

No significant difference in results was observed between subcutaneous administration of rhGM-CSF and continuous i.v. infusion and these patient groups could therefore be combined in the analysis.

Administration of rhGM-CSF resulted in a significant dose-dependent increase of total WBC, mainly neutrophils, eosinophils and monocytes. The increase was observed in 18/24 patients, reaching a peak 24-72 (median 24) hours after the start of rhGM-CSF. The CHOP chemotherapy-induced leucocyte nadir occurred on day 12 (mean) compared to day 14 for the 127 historical controls. The WBC nadir values were higher (2.4 ± 1.4) than for historical controls (1.8 ± 1.1) and the leucopenic/neutropenic period was of shorter duration. Following the chemotherapy nadir a more rapid recovery of WBC was seen than in controls. GM-CSF was well tolerated, the side effects were mild and transient, and included myalgias, low grade fever, headache, chest/bone discomfort, nausea, erythema at injection site and superficial phlebitis.

The encouraging results of this phase I/II study indicate the need for a prospective controlled study of GM-CSF in chemotherapy of malignant lymphoma.     

Ifosfamide,Cisplatin and Etoposide (ICE)Combined Chemotherapy with Recombinant Human Granulocyte Colony-Stimulating Factor Support in Small Cell Lung Cancer

Abstract

This study was aimed to evaluate the effect of ifosfamide, cisplatin and etoposide (ICE) combined chemotherapy in small cell lung cancer (SCLC), and to test the feasibility of adding recombinant human granulocyte colony-stimulating factor (rhG-CSF) to aggressive chemotherapy. Thirty consecutive, previously untreated, patients with SCLC (17 with limited disease and 13 with extensive disease) entered this study. The ICE regimen consisted of ifosfamide (I) 4 g/m² i.v. with same dose mesna i.v. on first day, cisplatin (C) 25 mg/m² i.v. on days 1 to 3 and etoposide (E) 100 mg/m² i.v. on days 1 to 3. A total of 30 MU rhG-CSF i.v. were given from day 7 to 14 if WBC were lower than 3000x10⁶/L, neutrophils were lower than 1000x10⁶/L. Overall response (OR) rate was 93% with a complete response (CR) rate of 23%. Median survival was 12 months [95% confidence interval (CI): 11-14] and median response duration was 10 months [95% CI: 8-10]. Thirty-seven percent of patients had grade 3 neu-tropenia, 40% had grade 3 anemia, and 1% had grade 2 thrombocytopenia. Nonhematologic toxicity was mild with nausea and vomiting being the most common. RhG-CSF, which reduced leukopenic nadirs and shortened the neutropenic period, was also well tolerated. This chemotherapy protocol seems to be active, well tolerated and is currently being compared with various conventional chemotherapies.