——Zolinza（vorinostat）
药品产地：美国新泽西州Whitehouse Station的Merck公司
药品介绍：
组蛋白去乙酰酶抑制剂
美国FDA今天批准Zolinza（通用名：vorinostat）胶囊用于治疗一种皮肤癌——皮肤T细胞淋巴瘤（cutaneous T-cell lymphoma，CTCL），用在当该病持续、恶化或在用其他药治疗期间或之后复发之时。
Zolinza是作为FDA的罕见病药品项目被批准的，FDA的罕见病药品项目给一些公司提供了资金激励，旨在开发用于每年影响少于20万美国人的疾病的药品。美国每年大约100万人中有3个人被诊断患有CTCL。大部分患有CTCL的人是男性，平均年龄50岁。
“这个批准是现代研究的益处另一个例子，现代研究关注给处方者提供对所有类型的癌症都安全有效的疗法，包括那些影响相对较少患者的癌症，”FDA的CDER主任Steven Galson医学博士称。
Zolinza的安全性和有效性证据是在对107位CTCL患者的两项临床试验中获得的，他们在用其他药治疗疾病又复发之后使用了Zolinza。接受Zonlinza的患者30%有响应，并且平均持续168天，这个响应的定义是通过皮肤损伤得分的改善来衡量的。最常见的严重不良事件是肺栓塞(肺部的血液凝块)、脱水、贫血、深部静脉血栓。最常见的不良事件是胃肠症状(包括腹泻、恶心、厌食、呕吐、便秘)；疲劳；畏寒；味觉异常。
Zolinza未在孕妇中做过临床研究，但是动物试验表明该药如果在怀孕期间使用可能造成胎儿伤害。
Zolinza是由加拿大安大略省的Mississauga市的Pantheon公司为美国新泽西州Whitehouse Station的Merck公司生产的。

Vorinostat for cutaneous T-cell lymphoma

Company:

Merck

Pharmacologic class:
Antineoplastic (histone deacetylase inhibitor)

Active ingredient:
Vorinostat 100mg; caps.

Indication:
Refractory cutaneous T-cell lymphoma.

Pharmacology:
Cutaneous T-cell lymphoma (CTCL) is a form of non-Hodgkin抯 lymphoma that affects the skin. Vorinostat is indicated for the treatment of the cutaneous manifestations associated with this cancer in patients who have progressive, persistent, or recurrent disease while on or after the use of two systemic therapies.

In some cancer cells, there is an overexpression of histone deacetylases (HDAC). This can interfere with the activation of genes that are involved in the regulation of cell growth. Vorinostat inhibits the activity of several of these HDACs. In doing so, it allows for the activation of genes that can control the growth of cancer cells. The exact mechanism of action for vorinostat in treating CTCL is unclear.

Clinical trials:
In an open-label, single-arm, multicenter study, 74 patients with advanced CTCL were treated with vorinostat 400mg/day. The extent of skin disease was measured by investigators using a score that took into account the percentage of body surface area affected and the severity of the lesions. The overall objective response rate was 29.7% in all patients treated with vorinostat.

An open-label, non-randomized study was conducted in 33 patients to determine the response rate for patients with CTCL who were refractory to or intolerant of at least one treatment. Patients were divided into three cohorts who received vorinostat in various dosing regimens. The primary efficacy endpoint was measured by a 7-point Physician抯 Global Assessment scale. A complete clinical response was defined as 100% clearing of all lesions, and a partial response was defined as at least 50% improvement in disease findings. The overall response rates were 30.8% for patients given vorinostat 400mg once daily, 9.1% for those given 300mg twice daily, and 33.3% for patients given vorinostat 300mg twice daily for 14 out of 21 days.

Adults:
Take with food. Swallow whole. 400mg once daily. If not tolerated, may reduce to 300mg once daily, then to 300mg once daily 5 days/week if needed. Continue until disease progression or not tolerated.

Children:
<18yrs: not recommended.

Precautions:
Congenital long QT syndrome. Hepatic impairment. Monitor for DVT, pulmonary embolism. Correct electrolyte disturbances before starting therapy. Maintain adequate hydration. Monitor CBC, platelets, blood glucose, serum creatinine, electrolytes (esp. potassium, calcium, magnesium) every 2 weeks for 1st 2 months, then monthly. Do baseline and periodic ECGs. Pregnancy (Cat.D). Nursing mothers: not recommended.

Interactions:
Increased risk of thrombocytopenia and GI bleed with other HDAC inhibitors (eg, valproic acid). Caution with other drugs that can cause QTc prolongation. Monitor warfarin.

Adverse reactions:
GI upset, fatigue, chills; thrombocytopenia, anemia (may need to modify dose or discontinue); anorexia, dysgeusia, pulmonary embolism, DVT, QTc prolongation, hyperglycemia.

Additional patient information:
Drink at least 2L fluid daily. Report excess vomiting/diarrhea to prescriber.
Zolinza的副作用药品不良反应
Zolinza（Vorinostat）是用于治疗一种名为皮肤T细胞淋巴瘤的疾病的处方药。患此病的患者如使用其他药物治疗后症状恶化并未好转，或者又复发的时候可选用Zolinza进行治疗。Zolinza还未进行在18岁以下儿童身上的应用研究。以下列举的是使用Zolinza疗法可能面临的主要风险及副作用。

列表中的内容并不能完全列举，如果患者在使用中出现以下任何症状请立即告知医生：
1.腿部出现血块凝集（深静脉血栓形成）
2.一条腿出现突然肿胀
3.腿部出现疼痛或触痛，且只有在站立或行走时才能感觉到这种疼痛
4.局部出现发热，且肿胀部位的皮肤出现发红或颜色改变
5.血液凝块游走至肺部（肺栓塞）
6.突然发作的尖锐胸痛
7.脉搏急促
8.气短
9.晕厥
10.咳出血性分泌物
11.焦躁不安
12.多汗
13.脱水，这可能发生在患者出现恶心、呕吐或腹泻后没能及时补液的情况
14.全血细胞计数降低：患者的医生应定期为患者做血液检测以检查血细胞计数
15.红细胞降低。红细胞降低可能让患者容易疲倦或感觉疲劳。患者可能出现苍白，气短
16.血小板降低。血小板降低可能导致皮下的异常出血或容易碰伤，这种情况出现时应立即告知医生
17.高血糖。如果患者本身有高血糖或糖尿病，应在医生指导下时常监测血糖。如果患者血糖高于正常应立即告知医生
18.心电图异常。心电图（又叫EKG）是用于记录心脏心电活动的方式。医生应定期检查患者的血电解质及心电图。
Zolinza最常见的副作用还包括：肠胃问题（如腹泻、恶心、呕吐、纳差，便秘和体重降低），疲乏，头晕，头痛，口干及味觉异常，肌肉疼痛，脱发，寒战，发热，上呼吸道感染，咳嗽，血肌酐升高，以及足部、踝部或腿部的肿胀或搔痒。