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美国FDA于2009年11月6日批准注射用药物Istodax（romidepsin）治疗皮肤T淋巴细胞瘤（CTCL）。CTCL为一种生长缓慢并且能够影响T淋巴细胞的肿瘤。大多数病例以皮肤干燥、红疹和瘙痒为首发症状，并且症状会逐渐加重。皮肤形成肿瘤后可发生溃疡，进而引发感染。在某些情况下CTCL可播散至血液、淋巴结及内脏器官。美国每年约有1500例新发病例。
皮肤局限性CTCL患者可采用局部药物治疗或光疗，如果肿瘤进展则可使用化疗。Istodax能够干扰细胞增殖的关键进程。当CTCL患者出现病情恶化或化疗后复发时，可考虑将Istodax用于治疗。两项共涉及167例患者的临床试验对Istodax进行了评价，研究中均有约35%的患者出现肿瘤缓解，其中一项研究的平均缓解时间为15个月，另一项为11个月，研究中有6%的患者出现完全缓解。
Istodax常见的副作用包括恶心、疲劳、感染、呕吐、食欲减退、红细胞降低、血小板减少和白细胞降低。Istodax还可能导致心电图（ECG）发生变化。使用该药物时应定期监测电解质，具有心律不齐风险者应定期监测ECG。Istodax可能对胎儿具有不良影响，因此女性在使用期间应避免受孕。
既往批准治疗CTCL的药物包括伏立诺他（Zolinza，vorinostat）、一种白介素融合2毒素（Ontak，denileukin difitox）和贝沙罗汀（Targretin，bexarotene）。
Manufacturer:
Celgene Corp
Pharmacological Class:
Antineoplastic (histone deacetylase inhibitor)
Active Ingredient(s):
Romidepsin 10mg/vial; pwdforIVinfusionafterreconstitution and dilution; contains povidone.
Indication(s):
Cutaneous T-cell lymphoma (CTCL) in patients who have received at least one prior systemic therapy.
Pharmacology:
Histone deacetylases catalyze the removal of acetyl groups from acetylated lysine residues in histones and non-histone proteins, affecting the expression of genes. Inhibitors of this enzyme, such as romidepsin, interfere with activities mediated by histones and transcription proteins.
In vitro, romidepsin has been shown to cause the accumulation of acetylated histones and to induce cell cycle arrest and apoptosis in some cancer cell lines, but its exact mechanism of action in treating CTCL has not been elucidated.
Clinical Trials:
Two multicenter, single-arm clinical studies were used to evaluate the efficacy of romidepsin in treating CTCL. Patients were treated with the study drug at the recommended dose until disease progression at the discretion of the investigator and local regulators. Objective disease response was evaluated using a composite endpoint that included assessments of skin involvement, lymph node and visceral involvement, and abnormal circulating T-cells.
The primary endpoint for each study wasoverallobjective disease response rate (ORR), defined as the proportion of patients with confirmed complete response or partial response.
Study 1 included 96 patients with confirmed CTCL after failure of at least 1 prior systemic therapy.
The ORR in this study was 34% (complete response 6% + partial response 28%). Median duration of response was 15 months.
Study 2 included 71 patients with a primary diagnosis of CTCL who received at least 2 prior skin directed therapies or at least one systemic therapy.
In this study, the ORR was 35% (complete response 6% + partial response 30%). Median duration of reponse was 11 months.
The median time to first response was 2 months in both studies.
The median time to complete response was 6 months in Study 1 and 4 months in Study 2.Legal Classification:
Rx
Adults:
≥18yrs: Give by IV infusion over 4hrs. 14mg/m2 on days 1, 8, and 15 of a 28-day cycle; repeat cycle every 28 days; continue as tolerated and as beneficial. May interrupt, reduce dose to 10mg/m2, or discontinue based on toxicities (seeliterature).
Children:
<18yrs: not recommended.
Precaution(s):
Correct electrolyte imbalances (esp. K+, Mg++) before starting. Monitor ECG and electrolytes in congenital long QT syndrome, significant cardiovascular disease. Moderate to severe hepatic impairment. End-stage renal disease. Monitor CBC with differential. Pregnancy (Cat.D; may cause fetal harm). Nursing mothers: not recommended.
Interaction(s):
May interfere with hormonal (estrogen) contraceptives. Caution with other drugs that can cause QT prolongation (monitor). Monitor PT/INR with warfarin. Potentiated by drugs that inhibit P-glycoprotein and CYP3A4;
avoid concomitant strong CYP3A4 inhibitors (eg, azole antifungals, protease inhibitors, clarithromycin, nefazodone). Caution with moderate CYP3A4 inhibitors. Antagonized by strong CYP3A4 inducers (eg,carbamazepine, phenytoin, phenobarbital, rifampin; avoid. Concomittant St.
John’s Wort: not recommended.
Adverse Reaction(s):
GIupset,fatigue,infections,anorexia,anemia,thrombocytopenia, ECGTwavechanges, neutropenia, lymphopenia.
How Supplied:
Kit—1 (single-use vial + diluent and supplies)
Last Updated:
3/4/2010
制造商：
Celgene公司公司
药理分类：
抗肿瘤（组蛋白去乙酰酶抑制剂）
活性成分（补）：Romidepsin 10mg/vial;为四输液密码重组和稀释后，包含聚维酮。
指示（补）：
治疗皮肤T淋巴细胞瘤（CTCL）。（CTCL的）。
药理：
组蛋白脱乙酰酶催化来自非组蛋白和赖氨酸残基乙酰乙酰基去除组蛋白，从而影响基因的表达。这种酶抑制剂，romidepsin，干扰组蛋白和转录介导的蛋白质的活动。在体外romidepsin已被证明导致组蛋白的乙酰化积累，促使某些肿瘤细胞株细胞周期阻滞和凋亡，但其确切作用机制CTCL的治疗尚未阐明。
临床试验：
两个多中心，单臂临床研究，来评估治疗皮肤T细胞淋巴癌的romidepsin疗效。患者治疗药物的研究在建议的剂量，直到病情在调查和当地的监管权进展。目标疾病的反应进行了评估使用复合终点，其中包括参与评估，皮肤，淋巴结及内脏的参与，以及不正常循环T细胞。每个研究的主要终点是总的目标疾病的反应效率（ORR），作为与患者比例界定确认完全缓解或部分缓解。
1包括96个研究与证实后，至少有1前全身治疗失败CTCL患者。在本研究Orr曾34％（完全缓解6％+部分缓解28％）。中位缓解时间为15个月。
研究2中包含的71 CTCL的谁的至少接受2之前，初步诊断病人皮肤直接疗法或至少一个全身治疗。在这项研究中，氧还原为35％（完全缓解6％+部分缓解30％）。中位缓解时间为11个月。
中位时间为第一个反应是这两项研究的2个月。中位数的时间完成了6个月的反应研究中的1和第4研究中的2个月。
法律分类：
接收
成人：
≥18yrs：由四输注给了4小时。 14mg/m2的天1，8和1 28 15天周期，重复周期每28天;继续作为容忍和有益的。
5月中断，减少剂量10mg/m2，或停止基于毒性（见文献）。
儿童：
“18yrs：不推荐。
预防措施（补）：
纠正电解质失衡（特别是钾，镁++）开始之前。监测心电图和先天性长QT综合征的电解质，重要的心血管疾病。中度至重度肝损害。终末期肾病。央行监测的差距。妊娠（Cat.D，可能会对胎儿造成伤害）。哺乳母亲：不推荐。
互动（补）：
可能会干扰荷尔蒙（雌激素）的避孕药具。注意与其他药物可能导致QT间期延长（监视器）。监视器葡萄牙/法林起始子。通过药物抑制P -糖蛋白和CYP3A4Potentiated，避免随之而来的强烈的CYP3A4抑制剂（如氮唑类抗真菌，蛋白酶抑制剂，克拉霉素，奈法唑酮）。注意中度CYP3A4抑制剂。
CYP3A4的诱导剂强拮抗（如卡马西平，苯妥英，苯巴比妥，利福平;避免。Concomittant贯叶连翘：不推荐。
不良反应（补）：
胃肠不适，疲劳，感染，厌食，贫血，血小板减少，心电图T波变化，中性粒细胞，淋巴细胞。
如何提供：
洁1（单用小瓶+稀释剂和用品）
最后更新：
2010年3月4日 | 
