欧盟批准西班牙Pharma Mar S.A.的Yondelis（trabectedin）用于晚期软组织肉瘤治疗。Yondelis的活性成分trabectedin是从海洋生物海鞘（sea squirts）中提取物的四氢喹啉类生物碱的半合成产品。临床试验剂量是每3周1次，每次1.5mg/m2，24小时静脉滴注。欧盟批准的依据是一项国际随机临床试验，270例患者接受两种不同剂量治疗：一是每3周1次，每次1.5mg/m2，24小时静脉滴注；另一是每周给药0.58mg/m2，静滴3小时，共3周，28天一循环。所有患者在给予trabectedin 前30分钟先给予地塞米松20mg静脉注射。结果前一种给药方法的效果显著优于后一种。每3周给药与每周给药的主要终点（进展时间）分别是3.7个月和2.3个月。次要终点（无进展存活中位数时间）分别是3.3个月和2.3个月，中位数存活时间分别是13.8个月和11.8个月。尽管这一剂量有稍多的不良反应（中性白细胞减少，可逆的肝酶升高，呕吐和疲劳），总体耐受尚好，而且没有累积毒性出现。
本品在2001年5月批准作为罕见病药物使用，2007年9月正式批准上市。本品的开发和获得批准在国外较受欢迎，原因是在过去30多年来，这是治疗软组织肉瘤的第一个上市新药。这对于常规化疗（阿霉素和异环磷酰胺）失败的晚期软组织肉瘤患者将是一个重要的新选择。

Yondelis infusion contains thactive ingredient trabectedin which is a type of chemotherapy medicine for cancer known as an ‘anti-neoplastic’.
Trabectedin is a naturally occurring compound that is derived from a marine organism, Ecteinascidia turbinate.

Cancers form when cells within the body multiply abnormally and uncontrollably.
These cells spread, destroying nearby tissues.
Trabectedin works by stopping the cancer cells from multiplying.
It does this by binding to and damaging the DNA in the cancer cells.
This stops the cells from growing and multiplying.

In most chemotherapy regimens, doses are administered in courses at various intervals to allow normal cells to recover from the adverse effects of the anticancer medicines between doses.
However, during this period, cancer cells will also recover and start to replicate again.
Successful treatment depends on the administration of the next course of therapy before the cancer has regrown to its previous size and the net effect is to decrease the amount of cancer with each successive course.

Trabectedin is used to treat a type of cancer known as soft tissue sarcoma, which affects muscles, fatty tissue and other soft tissue, such as cartilage or blood vessels.

Unfortunately, trabectedin can also affect normal, healthy cells, particularly those that multiply quickly, such as healthy blood cells.
Trabectedin is therefore only used to treat soft tissue sarcoma in people who have enough healthy cells in their blood at the start of treatment.
Regular blood tests are needed to monitor the levels of blood cells.

Trabectedin is given by slow infusion (drip) into a vein (intravenously) over 24 hours. Dexamethasone is always given before treatment with trabectedin to help reduce sickness and protect the liver.
The treatment is repeated every three weeks, for as many courses as your specialist feels is necessary.

What is it used for?

Soft tissue sarcoma.

This medicine is used when other medicines have not been effective or are unsuitable.

Warning!

Before each treatment with Yondelis you will need to have blood tests to check your blood cells, liver function, kidney function, bilirubin level and CPK level.
These tests should also be carried out weekly during your first two treatments.

This medicine can cause a decrease in the normal amounts of blood cells in the blood. For this reason you should consult your doctor immediately if you experience any of the following symptoms: unexplained bruising or bleeding, purple spots, sore throat, mouth ulcers, high temperature (fever), feeling tired or general illness. Your doctor may want to take a blood test to check your blood cells.

This medicine may have side effects on the muscles.
For this reason, you should inform your doctor immediately if you experience muscular symptoms such as pain, tenderness, cramps, or weakness while taking this medicine, particularly if they are accompanied by a fever or feeling generally unwell. Your doctor may need to check for side effects on the muscles by taking a blood test to measure the level of a compound called creatinine phosphokinase (CPK) in your blood.

This medicine may also have side effects on your liver.
Symptoms that may suggest a liver problem include persistent nausea and vomiting, abdominal pain, or the development of jaundice (a yellow colouring to the skin and the whites of the eyes).
Consult your doctor if you experience any of these symptoms.

You should not drink alcohol while having treatment with this medicine because this may increase the chance of side effects on the liver.

This medicine may be harmful to an unborn baby.
For this reason, women being treated with this medicine who could get pregnant must use ahighlyeffectivemethodofcontraception to prevent pregnancy.
You will be given advice on which forms are suitable for you.
Contraception should be started before your treatment begins and continued for at least three months after your treatment is finished.
You should tell your doctor immediately if you think you could be pregnant at any point during treatment.

Men being treated with this medicine must use a condom to avoid fathering a child during their treatment and for at least five months after treatment is finished. There is a risk of irreversible infertility associated with Yondelis.
For this reason, men should discuss the possibility of sperm conservation with their doctor before starting treatment.

Use with caution in

Decreased kidney function.

Decreased liver function or liver disease.

Not to be used in

Severe or uncontrolled infection.

Breastfeeding.

People with high levels of bilirubin (a pigment produced by the liver).

People with severely decreased kidney function.

People with low numbers of white blood cells (neutropenia), platelets (thrombocytopenia) or haemoglobin in their blood.

People with raised liver enzymes or creatinine phosphokinase (CPK) levels.

This medicine is not recommended for children and adolescents.

This medicine should not be used if you are allergic to one or any of its ingredients. Please inform your doctor or pharmacist if you have previously experienced such an allergy.

If you feel you have experienced an allergic reaction, stop using this medicine and inform your doctor or pharmacist immediately.

Pregnancy and breastfeeding Certain medicines should not be used during pregnancy or breastfeeding.
However, other medicines may be safely used in pregnancy or breastfeeding providing the benefits to the mother outweigh the risks to the unborn baby.
Always inform your doctor if you are pregnant or planning a pregnancy, before using any medicine.

This medicine may cause serious birth defects in a developing baby. It should not be used during pregnancy unless considered essential by your doctor. Effective contraception should be used by women who themselves, or whose male partners,arereceiving treatment with this medicine.
Women should continue to use this contraception for at least three months after the medicine is stopped. Consult your doctor immediately if you think you could be pregnant.

Men being treated with this medicine should use condoms to avoid fathering a child, both during treatment and for five months after treatment is finished, if their partner could get pregnant and is not using contraception.
It is not known if this medicine passes into breast milk.
Women should not breastfeed during treatment with this medicine and for three months after stopping the treatment.

Side effects

Medicines and their possible side effects can affect individual people in different ways. The following are some of the side effects that are known to be associated with this medicine. Just because a side effect is stated here does not mean that all people using this medicine will experience that or any side effect.

Disturbances of the gut, such as nausea and vomiting, constipation, diarrhoea, indigestion, abdominal pain.

Decrease in the numbers of white blood cells (neutropenia), platelets (thrombocytopenia) or red blood cells (anaemia) in the blood.

Fatigue, weakness or loss of strength (asthenia).

Loss of appetite and weight loss.

Headache.

Elevated levels of liver enzymes.

Injection site reaction.

Dizziness.

Problems with the nerves, for example causing changes in sensation such as pins and needles (paraesthesia) or numbness.

Shortness of breath (dyspnoea).

Pain in muscle or joints (myalgia or arthralgia).

Hair loss (alopecia).

Fever.

Low blood pressure (hypotension).

Swollen ankles (peripheral oedema).

Difficulty sleeping (insomnia).

Inflammation of the lining of the mouth (stomatitis).

Bacterial, viral or fungal infections, sometimes serious.

Muscle breakdown (rhabdomyolysis).

The side effects listed above may not include all of the side effects reported by the drug's manufacturer.

For more information about any other possible risks associated with this medicine, please read the information provided with the medicine or consult your doctor or pharmacist.

How can this medicine affect other medicines?

It is important to tell your doctor or pharmacist what medicines you are already taking, including those bought without a prescription and herbal medicines, before you start treatment with this medicine. Similarly, check with your doctor or pharmacist before taking any new medicines while having treatment with this one, to ensure that the combination is safe.

There may be an increased risk of side effects on the liver or blood cells if this medicine is used in combination with other medicines that can have these kinds of side effects, or with medicines that can prevent the breakdown of trabectedin in the body (see below for examples).

There may be an increased risk of side effects on the muscles if Yondelis is used in combination with any of the following medicines:

statins for lowering cholesterol, eg simvastatin, atorvastatinfibrates for lowering cholesterol, eg bezafibrate, gemfibrozil

ezetimibenicotinic acid (niacin)medicines that can prevent the breakdown of trabectedin in the body (see below for examples).

The following medicines may prevent the breakdown of trabectedin by the body and so may increase the risk of side effects:
azole antifungals, eg ketoconazole, fluconazoleciclosporinmacrolide antibiotics, eg clarithromycin.

protease inhibitors for HIV infection, eg ritonavir verapamil.

Trabectedin may decrease the blood level of phenytoin used to treat epilepsy, and this could increase the risk of convulsions.
The use of phenytoin in combination with Yondelis is not recommended.

The following medicines may decrease the amount of trabectedin in the blood and could therefore make it less effective:

phenobarbitalrifampicinthe herbal remedy St. John's wort.

Vaccines may be less effective in people receiving chemotherapy.

This is because chemotherapy medicines reduce the activity of the immune system and can prevent the body forming adequate antibodies.

Live vaccines should be postponed until at least six months after finishing chemotherapy because they may cause serious infections.
Live vaccines include: measles, mumps, rubella, MMR, BCG, oral polio, oral typhoid and yellow fever.

Other medicines containing the same active ingredient

There are currently no other medicines available in the UK that contain trabectedin as the active ingredient.
       据驻西班牙大使馆经商参处报道，西班牙Zeltia生物制药集团公司近日对外界宣布，欧盟委员会已经批准该集团下属的PharmaMar公司销售治癌新药Yondelis。今年7月，经欧洲药品评估机构EMEA核准，Yondelis这种专门用于治疗软组织恶性肿瘤(STS)的药品可以在欧盟27个成员国销售。软组织恶性肿瘤是对肌肉、骨骼和血管组织具有非常强的侵袭性的癌症，过去30年内治疗这类癌症(STS)的药物一直没有新的发展。Yondelis是第一个获EMEA批准、由西班牙研究的抗癌药成果，也是PharmaMar公司经过20年的研究，第一个从实验室成功进入市场的产品。PharmaMar公司专门从海洋生物组织中获取治癌物质，Yondelis中的ET-743活性物质就是从一种会喷射很强毒素以避免被肉食的海洋生物提取的，这种毒素对癌细胞有进攻性。

Yondelis的活性成分trabectedin是从海洋生物海鞘（sea squirts）中提取物的四氢喹啉类生物碱的半合成产品。临床试验剂量是每3周1次，每次1.5mg/m2，24小时静脉滴注。欧盟批准的依据是一项国际随机临床试验，270例患者接受两种不同剂量治疗：一是每3周1次，每次1.5mg/m2，24小时静脉滴注；另一是每周给药0.58mg/m2，静滴3小时，共3周，28天一循环。所有患者在给予trabectedin 前30分钟先给予地塞米松20mg静脉注射。结果前一种给药方法的效果显著优于后一种。每3周给药与每周给药的主要终点（进展时间）分别是3.7个月和2.3个月。次要终点（无进展存活中位数时间）分别是3.3个月和2.3个月，中位数存活时间分别是13.8个月和11.8个月。尽管这一剂量有稍多的不良反应（中性白细胞减少，可逆的肝酶升高，呕吐和疲劳），总体耐受尚好，而且没有累积毒性出现。
                                    
本品在2001年5月批准作为罕见病药物使用，2007年9月正式批准上市。本品的开发和获得批准在国外较受欢迎，原因是在过去30多年来，这是治疗软组织肉瘤的第一个上市新药。这对于常规化疗（阿霉素和异环磷酰胺）失败的晚期软组织肉瘤患者将是一个重要的新选择。
                                     
PharmaMar公司计划今年年底前首先在英国和德国销售Yondelis，期望在12个月内Yondelis能够覆盖75%的潜在市场。据报告，欧洲每年有14700个患STS的病例，其中30%适宜用Yondelis治疗.