简介:批准这份ozogamicin在复发急性髓系白血病(aml)。

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布罗斯PF, J,选自陈,陈XH达菲E,麻醉品L,罗伊,Sridhara R,拉赫曼,威廉姆斯G, Pazdur R

简介:批准这份ozogamicin在复发急性髓系白血病(aml)。

癌症研究杂志2001年6月,7 (6):1490 - 6。

PubMed ID

11410481 (在PubMed

]

文摘

目的:罗ozogamicin(麦;惠氏实验室、费城、PA)由calicheamicin的半合成衍生物,细胞毒性抗生素与重组单克隆抗体针对CD33的抗原存在于大多数患者急性髓系白血病成髓细胞白血病(AML)。在这项研究中,我们审查的临床前和临床资料immunoconjugate和监管审查,导致营销得到美国食品和药物管理局的批准。实验设计:从文学和制造商的数据,我们审查活动,耐受性、药动学和罗塔ozogamicin在临床前阶段我研究及其活动,疗效,副作用在三个阶段2试验142 AML患者复发。结果:在第一阶段的研究中,主要毒性myelosuppression,尤其是中性粒细胞减少和血小板减少,造成CD33在骨髓祖细胞的表达。第二阶段的剂量是9毫克/米(2)注入静脉输液/ 4 h,重复14天。少数患者急性输注相关症状,通常是短暂的,偶尔还需要住院治疗。完全缓解(CR)与造血作用全面复苏率为16%。病人的一个子集(与不完整的血小板恢复(crp) CRs)与爆炸间隙和嗜中性粒细胞恢复但不完全确定血小板恢复。c反应蛋白的反应时间似乎CRs的类似,虽然人数较少。 The question of the equivalence of these response groups was a central issue in the review of this new drug application (NDA). After considerable discussion, the Oncology Drugs Advisory Committee recommended allowing inclusion of CRps resulting in an overall response rate in the Phase 2 studies of 30%. In the subgroup of patients over 60 years of age, the overall response rate was 26%. Response duration was difficult to establish because of the high prevalence of postremission therapies. Tolerability and ease of administration may be improved compared with conventional chemotherapy, except for hepatotoxicity, with 31% of patients exhibiting abnormal liver enzymes. One patient died of liver failure in the Phase 2 trials. CONCLUSIONS: Marketing approval of gemtuzumab ozogamicin was granted on May 17, 2000 by the United States Food and Drug Administration under the Accelerated Approval regulations. Gemtuzumab ozogamicin is indicated for the treatment of patients with CD33 positive AML in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy. The approved dose was 9 mg/m(2) i.v. over 4 h and repeated in 14 days. Completion of the ongoing studies of gemtuzumab ozogamicin in relapsed AML and initiation of randomized clinical trials comparing the effects of gemtuzumab ozogamicin in combination with conventional induction chemotherapy to conventional chemotherapy alone on survival are mandated to confirm clinical benefit under the accelerated approval Subpart H regulations. Postmarketing reports of fatal anaphylaxis, adult respiratory distress syndrome (ARDS), and hepatotoxicity, especially venoocclusive disease (VOD) in patients treated with gemtuzumab ozogamicin, with and without associated hematopoietic stem cell transplantation (HSCT), have required labeling revisions and the initiation of a registration surveillance program. Tumor lysis and ARDS have been reported in patients with leukocytes above 30,000/ml treated with gemtuzumab ozogamicin; therefore, the reduction of leukocyte counts to below 30,000/ml is recommended prior to treatment. Patients should be carefully monitored for acute hypersensitivity, hypoxia, and delayed hepatotoxicity following treatment with gemtuzumab ozogamicin.

DrugBank数据引用了这篇文章

药物

罗塔ozogamicin

药物靶点

药物	目标	类	生物	药理作用	行动
罗塔ozogamicin	骨髓细胞表面抗原CD33	蛋白质	人类	是的	抗体 监管机构	细节