rhG-CSF预防恶性肿瘤化疗后粒细胞减少的Ⅱ期临床研究

目的：评价ｒｈＧ－ＣＳＦ（粒生素）对预防恶性肿瘤化疗后粒细胞减少的作用及不良反应。方法：人组总数６３例,均为病理或细胞学证实的恶性肿瘤。采用自身交叉方法将患者随机分入ＡＢ和ＢＡ两组。Ａ为治疗周期,即化疗用药结束４８ｈ开始,每日１次皮下注射ｒｈＧ－ＣＳＦ ５μｇ／ｋｇ,连续用药７～１４ｄ。Ｂ为空白对照周期。自化疗开始隔日查血常规１次,观察中性粒细胞（ＡＮＣ）及白细胞（ＷＢＣ）的变化。结果：治疗组于ｒｈＧ－ＣＳＦ注射２４ｈ后,ＷＢＣ及ＡＮＣ迅速上升,４８ｈ出现第１个高峰,第１０天出现第２个高峰,而对照组化疗后,ＷＢＣ和ＡＮＣ逐渐下降,始终低于治疗组。ＷＢＣ,ＡＮＣ的最低值、ＷＢＣ＜４．０×１０９／Ｌ、ＡＮＣ＜２．０×１０９／Ｌ的持续时间,以及化疗后第２１天ＷＢＣ＜４．０×１０９／Ｌ的病例数在治疗组和对照组间差异有显著性（Ｐ＜０．０５）。结论：ｒｈＧ－ＣＳＦ可以促进化疗患者ＷＢＣ和ＡＮＣ的恢复,耐受性良好,可以作为肿瘤化疗中提高剂量强度的有效辅助药。     

基因重组人粒细胞／巨噬细胞集落刺激因子防治肿瘤化疗所致的白？…

目的 研究基因重组人粒细胞／巨噬细胞集落刺激因子（ｒｈＧＭ－ＣＳＦ,生白能）防治实体瘤化疗所致白细胞（ＷＢＣ）和中性粒细胞（ＡＮＣ）减少的临床效果及不良反应。方法 采用多中心随机分组、自身交叉对照方法,对５７例肿瘤化疗患者随机分成ＡＢ组和ＢＡ组。ＡＢ组第１周化疗加生白能治疗（治疗组）,第２周期单用化疗（对照组）;ＢＡ组第１周期单用化疗,第２周期化疗加白能治疗。有５５例可做临床疗效分析。结果 生白能     

基因重组人粒细胞/巨噬细胞集落刺激因子防治肿瘤化疗所致的白细胞减少

目的研究基因重组人粒细胞／巨噬细胞集落刺激因子（ｒｈＧＭ－ＣＳＦ，生白能）防治实体瘤化疗所致白细胞（ＷＢＣ）和中性粒细胞（ＡＮＣ）减少的临床效果及不良反应。方法采用多中心随机分组、自身交叉对照方法，对５７例肿瘤化疗患者随机分成ＡＢ组和ＢＡ组。ＡＢ组第１周期化疗加生白能治疗（治疗组），第２周期单用化疗（对照组）；ＢＡ组第１周期单用化疗，第２周期化疗加生白能治疗。有５５例可做临床疗效分析。结果生白能可明显减轻化疗所致ＷＢＣ和ＡＮＣ下降程度，缩短ＷＢＣ和ＡＮＣ降至正常值以下的持续时间，促进ＷＢＣ和ＡＮＣ早日恢复，有助于化疗按期进行。主要不良反应有轻、中度发热，注射部位疼痛，骨骼肌肉疼痛，乏力和皮疹，一般可以耐受。结论生白能是一种有价值的化疗辅助药物。     

利百多预防肿瘤化疗所致白细胞减少的随机对比Ⅱ期临床研究

目的：为观察利百多（国产基因重组人粒细胞／巨噬细胞集落刺激因子,ｒｈＧＭ－ＣＳＦ）防治实体瘤化疗所致白细胞（ＷＢＣ）和中性粒细胞（ＡＮＣ）减少的临床效果及不良反应。方法：采用多中心随机分组、自身交叉对照方法,对６８例肿瘤化疗患者随机分成ＡＢ组和ＢＡ组。ＡＢ组第一周期化疗加利百多治疗（治疗组）,第二周期单用化疗（对照组）;ＢＡ组则第一周期单用化疗,第二周期化疗加利百多治疗。６０例可供临床疗效分析。结     

国产 rhG-CSF 预防肿瘤化疗所致白细胞减少的Ⅱ期临床研究

目的：考察国产重组人粒细胞集落刺激因子（ｒｈＧ－ＣＳＦ）对化疗患者的中性粒细胞的影响。方法：９６例经病理检查证实的恶性肿瘤，包括肺癌、恶性淋巴瘤、乳癌、卵巢癌等四种肿瘤病例，分别使用同样方案和剂量的化疗并采用交叉自身配对对照的方法，对这些化疗病例同时加用或不加用重组人粒细胞集落刺激因子注射液（吉粒芬）作对照研究，比较两组病人中性粒细胞绝对数（ＡＮＣ）的动态变化。结果：１９２个疗程不同化疗方案治疗几种肿瘤，并用国产ｒｈＧ－ＣＳＦ者，粒细胞减少症持续天数，ＡＮＣ减少（＜２．０×１０９／Ｌ）的发生率，化疗后ＡＮＣ最低值以及因ＡＮＣ过低致下一疗程化疗推迟的发生率，均优于空白对照组。注射国产ｒｈＧ－ＣＳＦ２４小时后ＡＮＣ迅速升高，多于第１０～１４天ＡＮＣ恢复至正常或更高水平。本组观察国产ｒｈＧ－ＣＳＦ除轻微肾瘤、肌肉痛外未见明显毒副反应。结论：国产ｒｈＧ－ＣＳＦ可减轻化疗后ＡＮＣ降低的程度，缩短粒细胞缺乏症的持续时间，促进ＡＮＣ的恢复，无明显毒副反应，可作为肿瘤化疗中有价值的辅助药物。     

同剂量国产rhG-CSF预防肺癌化疗所致粒细胞减少81例临床观察

目的观察不同剂量国产重组人粒细胞集落刺激因子（ｒｈＧＣＳＦ）对肺癌化疗患者中性粒细胞的影响以及对人体的毒副作用。方法８１例经病理证实的肺癌患者,采用相应的方案进行化疗。并于化疗后２４小时将患者分为３组采用低、中、高不同剂量的ｒｈＧＣＳＦ进行升白治疗,每组均为２７例。ｒｈＧＣＳＦ用法为：低剂量组（Ｔ３）７５μｇ／日,中剂量组（Ｔ２）１５０μｇ／日,高剂量组（Ｔ１）３００μｇ／日,均为皮下注射,每日１次,直至ＡＮＣ降至最低值后回升超过５０×１０９／Ｌ２次以上或已用１０天后停药;另高剂量组２７例采用自身交叉对照法,即该组患者共进行２周期化疗,其中１周期于化疗后加用３００μｇ者为高剂量组（Ｔ１）,另１周期不加用者为对照组（Ｃ）。比较不同剂量组中性粒细胞绝对数（ＡＮＣ）的动态变化。结果治疗组于化疗结束２４ｈ后并用ｒｈＧＣＳＦ能减轻粒细胞减少程度及缩短其持续时间。高剂量组效果最佳,中剂量组次之,即使低剂量组与对照组相比差异亦有显著性。本组观察国产ｒｈＧＣＳＦ除轻微骨痛、肌肉痛外未见其他明显毒副反应。结论国产ｒｈＧＣＳＦ可作为肿瘤化疗后预防ＡＮＣ下降的有价值的辅助药物     

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。     

肿瘤病人化疗、免疗及免疫化疗前后NK－IL－2－IFN－r系统变化

本文观察了４６例中晚期肿瘤病人化疗、免疗（抗瘤ｉＲＮＡ及Ｓ－ＴＦ）及免疫化疗前后ＮＫ－ＩＬ－２－ＩＦＮ－ｒ系统及ＷＢＣ等变化。结果发现：（１）肿瘤病人ＮＫ、ＩＬ－２及ＩＦＮ－ｒ活性均显著低于正常人；（２）化疗后除ＷＢＣ明显降低外，其它指标化疗前后均无明显变化；（３）免疫及免疫化疗后各免疫指标均较治疗前显著增加；（４）免化组各免疫指标及ＷＢＣ明显高于化疗组，其中ＩＬ－２及ＩＦＮ－ｒ活性还明显高于免疫组，但免疫组仅ＩＬ－２活性及ＷＢＣ明显高于化疗组。本研究结果表明，抗瘤ｉＲＮＡ及Ｓ－ＴＦ不仅可恢复肿瘤宿主的免疫力，而且与化疗联用，还可能降低化疗的毒副反应，协调肿瘤病人ＮＫ－ＩＬ－２－ＩＦＮ－ｒ系统的抗癌功能。     

基因重组人粒细胞／巨噬细胞集落刺激因子预防化疗所致白细胞减少症的临床疗效观察

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／巨噬细胞集落刺激因子（ＲｅｃｏｍｂｉｎａｎｔＨｕｍａｎＧｒａｎｕｌｏｃｙｔｓＭａｃｒｏｐｈａｇｅＣｏｌｏｎｙＳｔｉｍｕｌａｔｉｎｇＦａｃｔｏｒ，ｒｈＧＭ－ＣＳＦ，以下简称ｒｈＧＭ－ＣＳＦ）对ＣＥ及ＣＥＡ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。全组共２１例，其中Ａ组８例、Ｂ组１３例。结果表明，ｒｈＧＭ－ＣＳＦ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，降低其发生率，缩短白细胞和中性粒细胞降至正常值以下的持续时间，促进白细胞和中性粒细胞的早日恢复，但对血小板的变化影响不大。ｒｈＧＭ－ＣＳＰ的副反应主要是发热（４３％），此外还可见皮疹，感冒症状等。     

肿瘤病人化疗、免疗及免疫化疗前后NK－IL－2－IFN－r系统变化

本文观察了４６例中晚期肿瘤病人化疗、免疗（抗瘤ｉＲＮＡ及Ｓ－ＴＦ）及免疫化疗前后ＮＫ－ＩＬ－２－ＩＦＮ－ｒ系统及ＷＢＣ等变化。结果发现：（１）肿瘤病人ＮＫ、ＩＬ－２及ＩＦＮ－ｒ活性均显著低于正常人；（２）化疗后除ＷＢＣ明显降低外，其它指标化疗前后均无明显变化；（３）免疫及免疫化疗后各免疫指标均较治疗前显著增加；（４）免化组各免疫指标及ＷＢＣ明显高于化疗组，其中ＩＬ－２及ＩＦＮ－ｒ活性还明显高于免疫组，但免疫组仅ＩＬ－２活性及ＷＢＣ明显高于化疗组。本研究结果表明，抗瘤ｉＲＮＡ及Ｓ－ＴＦ不仅可恢复肿瘤宿主的免疫力，而且与化疗联用，还可能降低化疗的毒副反应，协调肿瘤病人ＮＫ－ＩＬ－２－ＩＦＮ－ｒ系统的抗癌功能。     

rhGM-CSF预防肿瘤化疗所致白细胞减少的随机对照临床研究

观察rhGM-CSF(重组人粒细胞 巨噬细胞集落刺激因子)预防和治疗肿瘤化疗所致白细胞(WBC)和中性粒细胞(ANC)减少的临床疗效和毒性反应。方法:采用随机自身交叉对照临床研究的方法,对64例病人进行化疗和rhGM-CSF治疗, 每一例病人连续观察2个周期。AB组病人第1周期为治疗组(A周期),采用化疗加rhGM-CSF治疗,第2周期为对照组(B周期),采用单纯化疗;BA组病人第１周期为对照组(B周期)采用单纯化疗,第２周期为治疗组(A周期)采用化疗加rhGM-CSF治疗。结果: 59例病人可评价疗效,治疗组WBC和ANC下降持续天数明显少于对照组,同时,WBC和ANC最低值也高于对照组,并且最低值时的中位化疗序日也比对照组明显提前,第21天时,治疗组WBC和ANC数值明显高于对照组,化疗延迟的例数治疗组明显少于对照组。结论: rhGM-CSF对化疗所致的白细胞和中性粒细胞减少具有明显的预防和治疗作用,保证化疗如期进行,不良反应可以耐受。     

格宁预防肿瘤化疗所致白细胞减少的随机对比研究

 为观察格宁(国产基因重组人粒细胞/巨噬细胞集落刺激因子, rhGM/CSF) 的临床效果和不良反应, 于1996年3月～ 1997年3月组织临床协作组对格宁进行了多中心随机、自身交叉对照的临床研究, 现报告其结果。     

Recombinant human granulocyte-macrophage colony-stimulating factor after combined chemotherapy in high-grade non-Hodgkin's lymphoma—a randomised pilot study

High-grade non-Hodgkin's lymphomas (NHL) can potentially be cured with combination chemotherapy, although the optimum schedules still have to be defined. Clinical trials with intensive chemotherapy are predominantly limited by myelosuppression. Here, haematopoetic growth factors open up the possibility of reducing chemotherapy-associated toxicities. In this randomised pilot study, we investigated the effects of a recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) following combined chemotherapy with vincristine, doxorubicin, cyclophosphamide, prednisone and etoposide (VACPE). A total of 35 patients with high-grade NHLs were randomised to receive either rhGM-CSF or placebo during the first two chemotherapy cycles and rhGM-CSF for all following cycles. rhGM-CSF was administered at a dosage of 5 μg/kg for 10 days or until neutrophils were > 1/nl following chemotherapy. The analyses revealed a significant reduction of neutropenia and duration of neutropenia in the rhGM-CSF group. Adverse events were rare and generally mild apart from one anaphylactoid reaction. No effects of rhGM-CSF were observed concerning the platelet nadir or duration of thrombocytopenia. The benefit of rhGM-CSF for response induction and survival via rhGM-CSF-supported dose intensification remains to be determined.     

Mitoxantrone/high-dose Ara-C and recombinant human GM-CSF in the treatment of refractory non-Hodgkin's lymphoma. A pilot study

Previous study has shown that the combination of mitoxantrone (Novantrone, NO) and Ara-C (AC) (NOAC) was active in refractory non-Hodgkin's lymphoma (NHL) but myelosuppression was dose-limiting. In a pilot study, we investigated the effects of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) after NOAC chemotherapy in patients with refractory NHL. NO was applied at a dosage of 10 mg/m2/day on days 2 and 3 and AC at 3 g/m2/12h on days 1 and 2. RhGM-CSF was administered at 250 ug/m2/day as a continuous i.v. infusion from day 6 until the neutrophils were greater than 3.0/nl for 3 consecutive days. Twenty-three patients from five of the nine participating centers were treated with NOAC chemotherapy plus rhGM-CSF, whereas 14 patients from the other four centers received chemotherapy alone. With rhGM-CSF, the median duration of severe neutropenia (less than 0.5/nl) after NOAC was 8 days versus a median of 13 days without rhGM-CSF (P = 0.0058), and that of thrombocytopenia (less than 20.0/nl), 3 days versus 7 days (P greater than 0.4, NS). The rates of infections and stomatitis were 25% and 17%, respectively, for patients treated with rhGM-CSF as compared to 53% (P = 0.0547, NS) and 60% (P = 0.0078), respectively, without rhGM-CSF. The following side effects were associated with the administration of rhGM-CSF: pleural and/or pericardial effusions in five patients, thrombosis in two patients, bone pain in two patients, and respiratory distress syndrome in one patient. A complete remission was achieved in nine of the 23 patients treated with NOAC plus rhGM-CSF, and in two of the 14 patients treated with chemotherapy alone. The median survival of patients treated with rhGM-CSF was not reached at 400 days and seemed to be longer than that of patients treated with chemotherapy alone (median, 109 days; P = 0.036). RhGM-CSF after chemotherapy can be applied safely to patients with NHL, shorten the period of severe cytopenia, reduce the rates of stomatitis, and did not seem to cause adverse effects on response.     

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。     

Increasing dose intensity of cisplatin-etoposide in advanced nonsmall cell lung carcinoma: a phase III randomized trial of the Spanish Lung Cancer Group

BACKGROUND: The authors designed this randomized, controlled trial to assess whether dose intensification of a cisplatin-etoposide combination (PE), achieved by shortening the interval between chemotherapy cycles, would improve response rate and survival. The maximum tolerated dose of PE was administered in either 3- or 4-week cycles to patients with advanced nonsmall cell lung carcinoma (NSCLC). METHODS: One hundred twenty-three patients were randomized into two groups. The dose-intense arm received cisplatin 35 mg/m2 and etoposide 200 mg/m2 on Days 1-3 every 4 weeks. The dose-dense arm received the same schedule every 3 weeks along with 5 microg/kg of recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) administered subcutaneously on Days 4-13. RESULTS: Patient characteristics were well balanced in both treatment arms. Fifty-four percent of patients were classified as Stage IIIB. A 32% increase in relative dose intensity was achieved in the dose-dense arm compared with the dose-intense arm. The response rates were 32% in the dose-intense arm and 27% in the dose-dense arm (P = 0.9). The median overall survival was higher in the dose-dense arm, 9 versus 7.2 months (P = 0.2). The main toxicity was myelosuppression, although the administration of GM-CSF significantly reduced the percentage of patients with Grade 4 granulocytopenia (53% vs. 78%). Fifty-four percent of the patients in the dose-intense arm and 35% of those in the dose-dense arm developed febrile neutropenia (P = 0.07). There were ten (8%) treatment-related deaths, three (4%) in the dose-intense arm and seven (12%) in the dose-dense arm (P = 0.3); three deaths in each arm were due to febrile neutropenia. CONCLUSIONS: The dose-intensification achieved in the dose-dense PE regimen did not correlate with significant improvements in response rate or survival and cannot be recommended in the light of the diversity of new drug combinations available today. However, the use of rhGM-CSF significantly reduced the incidence of severe granulocytopenia.     

Hematopoietic management in oncology practice. Part 1. Myeloid growth factors

Hematopoietic growth factors have transformed the practice of oncology. The two major factors in clinical use are recombinant human (rh) granulocyte colony-stimulating factor (G-CSF, filgrastin [Neupogen]) and granulocyte-macrophage colony-stimulating factor (GM-CSF, sargramostim [Leukine]). These factors differ significantly in their role in hematopoiesis and the regulation of mature effector cell function. G-CSF regulates both basal and neutrophil production and increased production and release of neutrophils from the marrow in response to infection. GM-CSF mediates its effects on the neutrophil lineage through its effects on phagocytic accessory cells and its synergy with G-CSF, but it does not appear to have a role in basal hematopoiesis. Part 1 of this two-part series focuses on the use of the myeloid growth factors rhG-CSF and rhGM-CSF to shorten the duration of chemotherapy-induced neutropenia and thus prevent infection in cancer patients. In randomized trials, rhG-CSF has consistently decreased the duration of neutropenia during all cycles of chemotherapy and reduced the risk of infection by 50% or more. Trials of rhGM-CSF have not reported consistent results.     

rhGM-CSF ameliorates neutropenia in patients with malignant glioma treated with BCNU.

Nitrosoureas are the drugs most effective in the treatment of patients with intracerebral malignant glioma. Their limiting toxicity is delayed myelosuppression. A prospective, randomised crossover study of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) was performed in patients receiving BCNU for relapsed glioblastoma, to investigate whether the resulting haematological toxicity profile could be modified by rhGM-CSF. Adequate data for analysis were obtained in 13 patients. Following BCNU, the nadir neutrophil count was higher in 12 out of 13 patients during the rhGM-CSF-protected cycles compared with the unprotected cycles. The median nadir was also significantly higher (1.79, CI 0.76-3.52, P < 0.005). Five episodes of neutropenia (< 2 x 10(9) l-1) occurred during the unprotected cycles compared with none in the rhGM-CSF-protected cycles (P = 0.076). There was no evidence of any effect on platelets. This result shows that the haematological toxicity profile following therapeutic doses of BCNU can be modified. It suggests that rhGM-CSF and other growth factors should be investigated for clinical efficacy in chemotherapy using nitrosoureas.