2014年7月3日，美国FDA批准Beleodaq (belinostat)用于外周T细胞淋巴瘤(PTCL)患者治疗，PTCL是一种罕见并快速增长的非霍奇金淋巴瘤(NHL)。这次的批准是在FDA加速批准程序下完成。
PTCL由不同组的疾病组成，这类疾病的淋巴结发生癌变。2014年，美国国家癌症研究所预测70800名美国人将被确诊为NHL，而有18990人会死亡。在北美，PTCL占NHLs的比例大约在10%到15%。
Beleodaq通过阻止有助于T细胞（一种免疫细胞）发生癌变的酶起作用。这款药物适用于治疗后（复发性）疾病又卷土重来或对以前治疗无效（难治性）的患者。
“这是自2009年以来获批用于外周T细胞淋巴瘤治疗的第三款药物，”FDA药品评价与研究中心血液及肿瘤产品办公室主任、医学博士Pazdur说。“今天的批准为患有这种严重及危及生命疾病的患者增加了一种可供使用的治疗选择。”
2009年，FDA加速批准普拉曲沙（Folotyn）用于复发或难治性PTCL患者，2011年批准罗咪酯肽（Istodax）用于之前至少接受过一种治疗的PTCL患者。
Beleodaq的安全性及有效性在一项由129名复发或难治性PTCL受试者参与的临床研究中得到评价。所有受试者均以Beleodaq治疗，直到他们的疾病发生恶化或副作用变得不可接受。结果显示，25.8%受试者的癌症在治疗后消失（完全缓解）或缩小（部分缓解）。Beleodaq治疗受试者最常见副作用有恶心、疲劳、发烧(发热)、低红细胞水平(贫血)和呕吐。
Beleodaq与普拉曲沙由Spectrum制药上市销售。Istodax由塞尔基因上市销售。
BELEODAQ Rx
Generic Name and Formulations:
Belinostat 500mg; per vial; lyophilized pwd for IV inj after reconstitution and dilution.
Company:
Spectrum Pharmaceuticals, Inc.
Indications for BELEODAQ:
Relapsed or refractory peripheral T-cell lymphoma.
Adult:
Give 1000mg/m2 once daily by IV infusion over 30 mins on Days 1–5 of a 21-day cycle; can repeat cycles every 21 days until disease progression or unacceptable toxicity. Dose modifications: Hematologic toxicities: if ANC nadir <0.5x109/L or platelet count <25x109/L: decrease dose by 25% (750mg/m2); discontinue if recurrent ANC <0.5x109/L or platelet count <25x109/L nadirs after 2 dose reductions; Non-hematologic toxicities: if any CTCAE Grade 3/4 reaction: decrease dose by 25% (750mg/m2); discontinue if recurrent CTCAE Grade 3/4 reaction after 2 dose reductions. Patients with homozygous UGT1A1*28 allele: initially 750mg/m2.
Children:
Not established.
Pharmacological Class:
Histone deacetylase inhibitor.
Warnings/Precautions:
Risk of hematologic toxicity; monitor blood counts with differential at baseline and weekly during therapy; adjust dose as necessary. Active infection: do not administer. History of extensive or intensive chemotherapy: may be at higher risk of life-threatening infections. Renal or hepatic impairment. Monitor serum chemistry, renal and hepatic function before treatment and the start of each cycle; interrupt, adjust, or discontinue dose based on severity of hepatotoxicity. Tumor lysis syndrome; monitor patients with advanced stage disease and/or high tumor syndrome. GI toxicity; may require use of antiemetics and antidiarrheals. Embryo-fetal toxicity. Pregnancy (Cat. D), nursing mothers: not recommended.
Interactions:
Avoid concomitant use of strong UGT1A1 inhibitors.
Adverse Reactions:
Nausea, fatigue, pyrexia, anemia, vomiting; hematologic toxicity, infection, hepatotoxicity, tumor lysis syndrome, GI toxicity.
How Supplied:
Single-use vial (30mL)—1