Zolinza是通过美国食品药品管理局（FDA）批准的一种最有效治疗皮肤癌新药Zolinza胶囊(vorinostat)。用于治疗皮肤T细胞淋巴瘤（CTCL），该药可用于皮肤癌持续恶化、其他药物治疗期间或以后复发。该药由美国默克公司生产。
皮肤T细胞淋巴瘤（CTCL）发病率较低，全美每年每100万人中约有3人诊断为CTCL。多数CTCL患者为男性，平均年龄50岁。根据相关法规，FDA按照罕见病治疗药物审批程序批准Zolinza，目的在于激励制药公司投资开发每年影响约20万美国人的罕见性疾病。
Zolinza的安全性和有效性的证据来自两项临床试验，其中包括对接受其他药物治疗后又复发的107名CTCL患者。按皮肤损伤评分等级的改善确定的标准分析，接受Zolinza治疗的30％患者有所改善，疗效平均持续168天。最常见的严重不良反应为肺栓塞、脱水、深度静脉血栓和贫血。常见的不良反应有胃肠症状（包括腹泻，恶心，食欲减退，呕吐和便秘）；疲惫，寒战和味觉障碍。动物实验结果显示，孕妇禁用该药。

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。

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

Generic name: Vorinostat

What is Zolinza?

Zolinza is used to treat cutaneous T-cell lymphoma (CTCL) in people who have already tried at least two different types of therapy.

What is the most important information I should know about Zolinza?

Zolinza may cause certain types of blood clots such as a pulmonary embolism or deep vein thrombosis. This drug may also cause anemia, excessive bleeding, or stomach problems such as nausea, vomiting, and diarrhea. It may also cause an increase in blood sugar.

Who should not take Zolinza?

Do not take Zolinza if you are pregnant or planning to become pregnant. This drug may cause severe harm to your unborn baby, including bone malformation and shortened life.

What should I tell my doctor before I take the first dose of Zolinza?

Mention all prescription, over-the-counter, and herbal medications you are taking before beginning treatment with Zolinza. Also, talk to your doctor about your complete medical history, especially if you have high blood sugar, blood clots, irregular heartbeats, or are pregnant or planning to become pregnant.

What is the usual dosage?

Adults: The usual dosage of Zolinza is 400 milligrams (mg) once daily.

How should I take Zolinza?

Zolinza capsules should be taken with food once per day. Drink at least 2 liters of water a day to stay well-hydrated. Report any nausea or vomiting to your doctor immediately.

What should I avoid while taking Zolinza?

Do not crush, chew, or open Zolinza. Avoid becoming pregnant while on Zolinza, as it may cause severe harm to your unborn baby.

What are possible food and drug interactions associated with Zolinza?

If Zolinza is used with certain other drugs, the effects of either could be increased, decreased, or altered. It is especially important to check with your doctor before combining Zolinza with blood thinners (especially coumarin derivatives) or valproic acid.

What are the possible side effects of Zolinza?

Side effects cannot be anticipated. If any develop or change in intensity, tell your doctor as soon as possible. Only your doctor can determine if it is safe for you to continue taking this drug.

Side effects may include: anemia, loss of appetite, chills, constipation, diarrhea, dry mouth, excessive bleeding, nausea, taste problems, tiredness, vomiting, weight loss

Can I receive Zolinza if I am pregnant or breastfeeding?

Do not take Zolinza if you are pregnant or planning to become pregnant. This drug may cause severe problems with the development of your baby's bones, and may shorten the child's life. Talk to your doctor if you are nursing; Zolinza may pass into breast milk.

What should I do if I miss a dose of Zolinza?

Take the missed dose as soon as you remember it. However, if it is almost time for your next dose, skip the one you missed and return to your regular dosing schedule. Do not double the dose.

How should I store Zolinza?

Store at room temperature.