Sargramostim

LEXINGTON, Mass., Feb. 20, 2026 /PRNewswire/ -- Partner Therapeutics, Inc. (PTx) announced findings from a post hoc analysis of the eNRGy trial (NCT02912949) evaluating treatment beyond progression with zenocutuzumab in patients with advanced neuregulin 1 fusion-positive (NRG1+) non-small cell lung cancer (NSCLC). Results were presented at the 2026 International Association for the Study of Lung Cancer (IASLC) Targeted Therapies of Lung Cancer (TTLC) meeting. NRG1+ NSCLC is associated with low response rates and poor outcomes with non-targeted therapies, underscoring the need for effective targeted treatment options such as zenocutuzumab and potential use beyond progression. "Patients with advanced NRG1 fusion-positive non-small cell lung cancer often have limited treatment options after progression," said Dr. Misako Nagasaka, MD, PhD of the University of California Irvine and senior author. "In this analysis, continued zenocutuzumab treatment beyond RECIST progression provided meaningful, sometimes long-lasting, clinical benefit while maintaining a favorable tolerability profile." The analysis included 27 patients with NRG1+ NSCLC who received at least three doses of zenocutuzumab after radiographic progression. Oligoprogression occurred in 81% of patients, while 19% experienced diffuse progression. Median total zenocutuzumab exposure increased to nearly 10 months, compared with approximately 7 months before progression. Eight patients continued treatment for more than six months beyond progression, including one patient remaining on zenocutuzumab for more than 23 months after progression, with treatment still ongoing as of December 2025. Another patient remained on zenocutuzumab for nearly four years in total. Additionally, 22% of patients were able to continue zenocutuzumab following local management of progressing lesions including radiotherapy, gamma knife surgery, and surgical resection. Treatment was generally well tolerated, and no patients discontinued therapy due to adverse events. "These data underscore the potential heterogeneity of disease at progression and provide evidence that continued use of a targeted therapy, like zenocutuzumab, may offer meaningful clinical benefit without introducing new safety concerns," said Pritesh J. Gandhi, Chief Development Officer at Partner Therapeutics. "We continue to work with physicians to generate more information on the use of zenocutuzumab beyond progression." In December 2024, zenocutuzumab-zbco (BIZENGRI®) received U.S. Food and Drug Administration accelerated approval for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. The indications were approved under accelerated approval based on ORR and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). NRG1 gene fusions and other gene fusions are best detected using the combination of tissue-based DNA and RNA next-generation sequencing. For more information on the eNRGy trial and zenocutuzumab-zbco, please visit . About NRG1 Gene Fusions NRG1 fusions are unique cancer drivers that create oncogenic chimeric ligands rather than the more widely described chimeric receptors (NTRK, RET, ROS1, ALK, and FGFR fusions). The chimeric ligands bind to HER3, triggering HER2/HER3 heterodimerization and activate downstream signaling pathways that cause cancer cells to grow and proliferate. Zenocutuzumab-zbco is a bispecific antibody that blocks HER2/HER3 dimerization and NRG1 fusion interactions with HER3, resulting in the suppression of these pathways. Comprehensive molecular testing, notably the combination of tissue-based DNA and RNA next generation sequencing, is essential to identify rare and actionable gene fusions like NRG1. About BIZENGRI (zenocutuzumab-zbco) INDICATIONS BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Important Safety Information BOXED WARNING: EMBRYO-FETAL TOXICITY Embryo-Fetal Toxicity: Exposure to BIZENGRI during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception. WARNINGS AND PRECUATIONS Infusion-Related Reactions/Hypersensitivity/Anaphylactic Reactions BIZENGRI can cause serious and life-threatening infusion-related reactions (IRRs), hypersensitivity and anaphylactic reactions. Signs and symptoms of IRR may include chills, nausea, fever, and cough. In the eNRGy study, 13% of patients experienced IRRs, all were Grade 1 or 2; 91% occurred during the first infusion. Administer BIZENGRI in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor patients closely for signs and symptoms of infusion reactions during infusion and for at least 1 hour following completion of first BIZENGRI infusion and as clinically indicated. Interrupt BIZENGRI infusion in patients with ≤ Grade 3 IRRs and administer symptomatic treatment as needed. Resume infusion at a reduced rate after resolution of symptoms. Immediately stop the infusion and permanently discontinue BIZENGRI for Grade 4 or life-threatening IRR or hypersensitivity/anaphylaxis reactions. Interstitial Lung Disease/Pneumonitis BIZENGRI can cause serious and life-threatening interstitial lung disease (ILD)/pneumonitis. In the eNRGy study, ILD/pneumonitis occurred in 2 (1.1%) patients treated with BIZENGRI. Grade 2 ILD/pneumonitis (Grade 2) resulting in permanent discontinuation of BIZENGRI occurred in 1 (0.6%) patient. Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold BIZENGRI in patients with suspected ILD/pneumonitis and administer corticosteroids as clinically indicated. Permanently discontinue BIZENGRI if ILD/pneumonitis ≥ Grade 2 is confirmed. Left Ventricular Dysfunction BIZENGRI can cause left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including BIZENGRI. Treatment with BIZENGRI has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment. In the eNRGy study, Grade 2 LVEF decrease (40%-50%; 10 – 19% drop from baseline) occurred in 2% of evaluable patients. Cardiac failure without LVEF decrease occurred in 1.7% of patients, including 1 (0.6%) fatal event. Before initiating BIZENGRI, evaluate LVEF and monitor at regular intervals during treatment as clinically indicated. For LVEF of less than 45% or less than 50% with absolute decrease from baseline of 10% or greater which is confirmed, or in patients with symptomatic congestive heart failure (CHF), permanently discontinue BIZENGRI. Embryo-Fetal Toxicity Based on its mechanism of action, BIZENGRI can cause fetal harm when administered to a pregnant woman. No animal reproduction studies were conducted with BIZENGRI. In post marketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In animal models, studies have demonstrated that inhibition of HER2 and/or HER3 results in impaired embryo-fetal development, including effects on cardiac, vascular and neuronal development, and embryolethality. Advise patients of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of BIZENGRI. Advise females of reproductive potential to use effective contraception during treatment with BIZENGRI and for 2 months after the last dose. ADVERSE REACTIONS NRG1 Gene Fusion Positive Unresectable or Metastatic NSCLC Serious adverse reactions occurred in 25% of patients with NRG1 gene fusion positive NSCLC who received BIZENGRI. Serious adverse reactions in ≥ 2% of patients included pneumonia (n=4) dyspnea and fatigue (n=2 each). Fatal adverse reactions occurred in 3 (3%) patients and included respiratory failure (n=2), and cardiac failure (n=1). Permanent discontinuation of BIZENGRI due to an adverse reaction occurred in 3% of patients. Adverse reactions resulting in permanent discontinuation of BIZENGRI included dyspnea, pneumonitis and sepsis (n=1 each). In patients with NRG1 gene fusion positive NSCLC who received BIZENGRI, the most common (>20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (35%), increased alanine aminotransferase (30%), decreased magnesium (28%), increased alkaline phosphatase (27), decreased phosphate (26%), diarrhea (25%), musculoskeletal pain (23%), increased gamma-glutamyl transpeptidase (23%), increased aspartate aminotransferase (22%), and decreased potassium (21%). NRG1 Gene Fusion Positive Unresectable or Metastatic Pancreatic Adenocarcinoma Serious adverse reactions occurred in 23% of patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI. There were 2 fatal adverse reactions, one due to COVID-19 and one due to respiratory failure. In patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased alanine aminotransferase (51%), diarrhea (36%), increased aspartate aminotransferase (31%), increased bilirubin (31%), decreased phosphate (31%), increased alkaline phosphatase (28%), decreased sodium (28%), musculoskeletal pain (28%), decreased albumin (26%), decreased potassium (26%), decreased platelets (26%), decreased magnesium (24%), increased gamma-glutamyl transpeptidase (23%), decreased hemoglobin (23%), vomiting (23%), nausea (23%), decreased leukocytes (21%), and fatigue (21%). Please see full Prescribing Information, including Boxed Warning About Partner Therapeutics Partner Therapeutics, Inc. (PTx), an integrated biotechnology company, focuses on development and commercialization of therapeutics to improve health outcomes in cancer and serious diseases, as well as global health security threats. The company believes in delivering products and supporting medical teams with the purpose of achieving superior outcomes for patients and their families. PTx's portfolio includes zenocutuzumab-zbco (BIZENGRI®) and sargramostim (EU: IMREPLYS®; US: LEUKINE®; and with Nobelpharma Co. Ltd for JAPAN: SARGMALIN®). Visit . References: 1. Arter ZL, Schram AM, Rha SY, et al. Continued treatment beyond progression with zenocutuzumab, a HER2/HER3 bispecific antibody, in patients with NRG1+ NSCLC: Analysis from the ongoing phase 2 eNRGy trial [abstract]. J Thorac Oncol. 2026. Poster presentation at International Association for the Study of Lung Cancer (IASLC) Targeted Therapies of Lung Cancer Meeting; Huntington Beach, CA; February 20, 2026. 2. Drilon A, Duruisseaux M, Han JY, et al. Clinicopathologic features and response to therapy of NRG1 fusion–driven lung cancers: The eNRGy1 global multicenter registry. J Clin Oncol. 2021;39(25):2791-2802. doi:10.1200/JCO.20.03307 3. BIZENGRI (zenocutuzumab-zbco) injection [package insert]. Available at: 4. Schram AM, Goto K, Kim DW, et al. Efficacy of zenocutuzumab in NRG1 fusion–positive cancer. N Engl J Med. 2025;392:566-76. doi: 10.1056/NEJMoa2405008 BIZENGRI® is a registered trademark owned by Merus B.V. Under an agreement with Merus, PTx has exclusive rights to develop, manufacture, and commercialize zenocutuzumab-zbco for the treatment of NRG1+ cancer in the U.S. and provide the product on a named-patient basis for this use outside of the U.S. pending future regulatory developments. PARTNER THERAPEUTICS®, IMREPLYS®, and LEUKINE® are registered trademarks owned by Partner Therapeutics, Inc. ©2026 Partner Therapeutics, All rights reserved. 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序章 高墙后的死亡阴影 1985年，美国马里兰州，国立癌症研究所的病房里，气氛凝重。41岁的乳腺癌患者伊芙琳正经历第三轮强化化疗。治疗在缩小肿瘤，但每一次化疗后，她的血常规报告就像一场定时审判——白细胞计数，尤其是中性粒细胞，会无情地跌入谷底。 这一次，数字跌得特别深。她的口腔开始出现溃疡，体温悄然攀升至39.5°C。经验丰富的肿瘤护士立刻拉响了警报：“中性粒细胞减少性发热！” 伊芙琳被迅速转入隔离病房。尽管使用了最强效的广谱抗生素，但在几乎没有“卫兵”（中性粒细胞）的身体里，细菌肆虐无忌。五天后，她死于难以控制的败血症休克。 在她主治医生的笔记本上，沉重地记录着：“死因：急性骨髓抑制导致的中性粒细胞缺乏性脓毒症。根本原因：缺乏有效的骨髓造血功能恢复手段。” 这一幕，在1980年代全球的肿瘤病房里反复上演。化疗如同一把双刃剑，在斩杀癌细胞的同时，也重创了骨髓这一“血细胞工厂”。中性粒细胞减少性发热及其导致的感染死亡，是当时限制化疗剂量、阻碍治愈率提升的最主要障碍。肿瘤学家们深知，若能筑起一道保护白细胞的“高墙”，就能让化疗这把剑挥得更彻底、更安全。 彼时，谁也不会想到，这道“高墙”的基石，竟源于二十多年前一位科学家对小鼠骨髓细胞培养皿中几个微小“斑点”的痴迷。 1 骨髓中的“星图” ——集落刺激因子理论的诞生 时间倒转至1961年，澳大利亚墨尔本，沃尔特与伊丽莎·霍尔医学研究所。一位名叫唐纳德·梅特卡夫的年轻科学家，正在尝试一项看似简单却前所未有的实验：他从小鼠的骨髓中提取出原始的造血细胞，将它们放在特制的半固体培养基（如琼脂）中培养。当时的普遍认知是，这些细胞在体外很快就会死亡。 然而，几天后，当梅特卡夫在显微镜下观察时，他看到了令他终身难忘的景象：在原本均匀的培养基背景上，星星点点地散布着一些微小的、不规则的细胞团。他敏锐地意识到，每一个“斑点”，都可能是一个造血细胞的后代——一个“集落”。更关键的是，他发现，只有向培养基中添加某些特定的组织提取液或条件培养基时，这些集落才会出现。 梅特卡夫做出了一个划时代的推论：体内一定存在一些可溶性的物质，它们像“生长指令”或“刺激因子”一样，指挥着原始的造血干细胞向特定的血细胞谱系（红细胞、粒细胞、巨噬细胞等）增殖和分化。他将这些假想的物质命名为 “集落刺激因子”。 在接下来的近二十年里，梅特卡夫及其团队如同宇宙学家绘制星图一般，系统地鉴定和描述了不同类型的CSF。他们发现，有些因子主要刺激粒细胞和巨噬细胞的形成（GM-CSF），有些则更专一地驱动粒细胞（G-CSF）或巨噬细胞（M-CSF）的发育。其中，G-CSF因其对中性粒细胞——这道抗感染前线最核心的“步兵”——的特异性促生成作用，显得尤为重要。 然而，整个1970年代，CSF都只是生物学概念和实验室现象。它们以微乎其微的量存在于复杂的生物体液中，化学本质不明，更遑论提纯和应用。梅特卡夫被誉为“CSF之父”，但他的发现，距离拯救病房里的伊芙琳，还隔着巨大的技术鸿沟。 2 基因猎手 ——从“现象”到“分子”的惊险一跃 转机伴随着1980年代分子生物学革命的浪潮而来。此时，美国加州的安进公司还是一家名不见经传的小型生物技术初创企业，正渴望在生物制药领域找到突破口。而CSF，这个已被基础研究充分验证的靶点，进入了他们的视野。 将G-CSF从一种“活性”变成一个可以大规模生产的“分子”，需要其基因序列。这是一场艰苦卓绝的“基因狩猎”。 策略一：蛋白质纯化引领的“苦行僧”之路。 一支团队试图沿用经典生物化学方法：从大量能产生G-CSF的细胞（如某些肿瘤细胞株）培养上清中，一步步纯化出微量的天然G-CSF蛋白，再通过测定其部分氨基酸序列，反向推导出可能的基因序列。这个过程如同大海捞针，需要处理成千上升的培养液，经历层析、电泳等无数步骤，进展缓慢，且最终得到的蛋白量可能只够做几次测序。 策略二：表达克隆的“奇袭”。 与此同时，安进的科学家村上浩等人采用了一种更新锐、更依赖运气和洞察力的策略——表达克隆。他们选择了膀胱癌细胞株5637，因为已知其条件培养基中含有高活性的G-CSF。他们提取了这些细胞的全部信使RNA（mRNA），并将其反转录成互补DNA（cDNA）文库，然后将这些cDNA片段分别转入可以表达外源基因的宿主细胞（如猴肾细胞COS）。 关键的一步在于检测。他们将每个转染了cDNA的COS细胞培养上清，加入到含有小鼠骨髓细胞的培养体系中，然后日夜观察，寻找那个能刺激中性粒细胞集落形成的“神秘上清”。这需要建立极其灵敏、稳定的生物测定方法，并对数十万个克隆进行逐一筛查。 1986年，经过无数次的失败与尝试，奇迹发生了。一个特定的cDNA克隆被鉴定出来，当它表达的产物被加入骨髓细胞培养体系时，大量纯净的粒细胞集落蓬勃生长。他们成功克隆了人粒细胞集落刺激因子的基因。随后的测序分析揭示了其编码的蛋白质：一段由174个氨基酸组成的多肽链。 几乎同时，日本中外制药的科学家也独立克隆了G-CSF基因。科学的竞赛，以人类共同的胜利告终。获得基因，意味着可以利用重组DNA技术，让细菌（如大肠杆菌）或哺乳动物细胞变成高效的“G-CSF工厂”，无限生产这种原本在自然界中极其稀缺的蛋白质。 3 从“细菌工厂”到患者体内 ——非格司亭的诞生 有了基因，安进公司面临下一个抉择：选择哪种表达系统？这决定了最终药物的形式。 · 大肠杆菌系统：产量高、成本低，但表达的是非糖基化的蛋白，其氨基酸序列的N端比天然人G-CSF多一个蛋氨酸（因此被称为“甲硫氨酸化G-CSF”）。 · 哺乳动物细胞系统：能产生糖基化的蛋白，更接近天然人G-CSF的形式。 安进最终选择了大肠杆菌系统，生产的产物被命名为 “非格司亭” 。深入的临床前研究证明，这个多了一个蛋氨酸的重组蛋白，在生物活性、与受体的结合能力上，与天然G-CSF完全等效，甚至在体内外稳定性上可能更优。 接下来是严峻的临床试验。首要问题是：它安全吗？在人体内，外源的G-CSF会不会过度刺激骨髓，导致不受控的白细胞增多甚至白血病？会不会引发严重的自身免疫反应？ I期临床试验在健康志愿者和少量癌症患者中启动。结果令人鼓舞：非格司亭表现出卓越的安全性和明确的剂量依赖性升白效应。皮下注射后，外周血中性粒细胞数量在24小时内开始上升，并在几天内达到高峰。主要副作用是轻微的骨痛（与骨髓腔内的细胞快速增殖和扩张有关），以及注射部位的局部反应，均是可预测且可管理的。未观察到剂量限制性毒性及白血病转化等严重安全事件。 真正的考验在于能否改变临床结局。关键的随机、双盲、安慰剂对照III期临床试验随即展开，对象是接受高强度化疗（如用于小细胞肺癌的CAE方案）的癌症患者。一组患者在化疗后接受非格司亭注射，另一组接受安慰剂。 数据揭盲时，差异犹如云泥： · 中性粒细胞减少的深度和持续时间：非格司亭组显著改善。 · 中性粒细胞减少性发热的发生率：从安慰剂组的100% 骤降至非格司亭组的约28%。 · 住院和抗生素使用：大幅减少。 · 化疗的完成情况：非格司亭组患者更能按计划、足量地接受后续化疗周期。 这些数据强有力地证明，非格司亭不仅能提升白细胞数字，更能切实地降低致命感染风险，保障化疗的顺利进行。 4 获批与变革 ——肿瘤治疗范式的重塑 1991年2月，基于确凿的临床试验证据，美国FDA迅速批准了非格司亭（商品名：Neupogen）上市，用于预防化疗引起的中性粒细胞减少症及其相关并发症。 它的影响立竿见影，并深远地重塑了肿瘤学： 1. 直接拯救生命：无数像伊芙琳一样的患者，因为有了这道“白细胞高墙”，得以安然度过化疗后的骨髓抑制期，感染死亡率大幅下降。 2. 解放化疗的潜力：肿瘤医生可以更积极地使用剂量更强、密度更高的化疗方案（如剂量密集型疗法），而无需过度担忧骨髓毒性。这对于追求治愈的淋巴瘤、乳腺癌、睾丸癌等疾病至关重要，直接提高了部分癌症的治愈率。 3. 改善患者生活质量：减少了因感染导致的住院、使用静脉抗生素和医疗干预，让患者的治疗过程更加平稳、门诊化。 4. 催生支持治疗专科：非格司亭的成功，确立并极大地丰富了“肿瘤支持治疗”这一重要专科的内涵，使其成为与抗癌治疗并驾齐驱的支柱。 然而，非格司亭并非完美。它的半衰期仅约3.5小时，患者需要在化疗后每天进行一次皮下注射，持续7到14天甚至更久。这对于本就身心俱疲的癌症患者而言，是额外的负担和痛苦。 5 从每日到每周 ——长效化革命的序曲 非格司亭的局限性，催生了下一代产品的研发。科学家们开始思考：能否让G-CSF在体内停留更久？ 答案便是蛋白质长效化技术。2002年，安进推出了培非格司亭。其核心技术是将一个大的惰性聚乙二醇分子连接到非格司亭上（PEG化）。这个大分子如同一把“隐形伞”，既保护了G-CSF免遭肾脏快速清除，又改变了其药代动力学，将半衰期延长至数十小时。 结果是一场患者体验的革命：每个化疗周期，仅需在化疗结束后注射一次培非格司亭，即可覆盖整个中性粒细胞减少的风险窗口。它继承了非格司亭所有的疗效，同时极大提升了便利性、依从性和生活质量，迅速成为临床新标准。 培非格司亭的成功，正是站在非格司亭这位巨人的肩膀上。没有非格司亭从0到1的验证（G-CSF的安全有效性、临床价值），就不会有从1到10的长效化改进。 尾声 不朽的基石 今天，非格司亭的原研药已过专利期，多种生物类似药上市，价格更加可及。在培非格司亭等长效药物广泛应用的时代，它或许不再是首选，但从未被遗忘。它依然是干细胞动员、儿童患者、经济欠发达地区的重要工具与首选方案，更是全球无数无力承担长效药物的患者们可靠的生命防线。 回望非格司亭的发现史，它是一首多声部的交响乐： · 基础科学的好奇心（梅特卡夫的集落）提供了乐章的主题。 · 生物技术的勇气（安进的基因狩猎和表达克隆）谱写了激昂的旋律。 · 临床医学的迫切需求（化疗患者的死亡阴影）赋予了它深沉的情感与动力。 · 严谨的临床验证则确保了整部作品的和谐与辉煌。 非格司亭的故事告诉我们，伟大的药物发现，往往始于对生命最基本现象（几个细胞集落）的追问，成于跨越学科壁垒的技术融合，最终服务于人类最根本的健康需求。它或许不是最闪亮的那颗星，但作为第一个成功应用于临床的造血生长因子，它无疑是现代肿瘤支持治疗乃至整个生物制药时代的一块不朽基石。在每一剂保障化疗顺利进行的长效升白针背后，都伫立着非格司亭——这位沉默而伟大的先驱。 向下滑动查看 参考文献 1.  Metcalf, D. (2010). The discovery of the colony-stimulating factors. International Journal of Hematology, 91(5), 875-882.  2. Bradley, T. R., & Metcalf, D. (1966). The growth of mouse bone marrow cells in vitro. Australian Journal of Experimental Biology and Medical Science, 44(3), 287-300.  3. Nagata, S., Tsuchiya, M., Asano, S., Kaziro, Y., Yamazaki, T., Yamamoto, O., ... & Yamazaki, T. (1986). Molecular cloning and expression of cDNA for human granulocyte colony-stimulating factor. Nature, 319(6052), 415-418.  4. Souza, L. M., Boone, T. C., Gabrilove, J., Lai, P. H., Zsebo, K. M., Murdock, D. C., ... & Altrock, B. (1986). Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science, 232(4746), 61-65.  5. Gabrilove, J. L., Jakubowski, A., Scher, H., Sternberg, C., Wong, G., Grous, J., ... & Clarkson, B. (1988). Effect of granulocyte colony-stimulating factor on neutropenia and associated morbidity due to chemotherapy for transitional-cell carcinoma of the urothelium. New England Journal of Medicine, 318(22), 1414-1422.  6. Crawford, J., Ozer, H., Stoller, R., Johnson, D., Lyman, G., Tabbara, I., ... & Smith, R. (1991). Reduction by granulocyte colony-stimulating factor of fever and neutropenia induced by chemotherapy in patients with small-cell lung cancer. New England Journal of Medicine, 325(3), 164-170.  7. Morstyn, G., & Foote, M. A. (2000). The history of granulocyte colony-stimulating factor. Hematology/Oncology Clinics of North America, 14(6), 1309-1333.  8.美国FDA药品说明书：Neupogen (filgrastim)的官方说明书，包含详细的药理学、临床试验数据和安全性信息。 9. Molineux, G. (2004). The design and development of pegfilgrastim (PEG-methionyl human granulocyte colony-stimulating factor, Neulasta). Current Pharmaceutical Design, 10(11), 1235-1244.  END 温馨提醒：本账号所有内容仅为科普分享，不能代替任何专业医疗建议。 封面图片为AI生成，请注意甄别。