Information on CLOLAR

What is Clolar?
Clolar (clofarabine) is a cancer medication that interferes with the growth of cancer cells and slows their growth and spread in the body.Clolar is used to treat acute lymphoblastic leukemia (a type of blood cancer) in children and young adults up to 21 years old.Clolar is usually given after other cancer medicines have been tried without successful treatment.
Important information about Clolar
Do not use Clolar without telling your doctor if you are pregnant. It could harm the unborn baby. Use birth control to prevent pregnancy while you are receiving Clolar, whether you are a man or a woman. Clolar use by either parent may cause birth defects.
If you have liver or kidney disease, you may need a dose adjustment or special tests to safely receive Clolar.
To be sure Clolar is not causing harmful effects, your blood cells, kidney function, and liver function may need to be tested on a regular basis. Do not miss any follow-up visits to your doctor.
Clolar can lower the blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill. Avoid being near people who have colds, the flu, or other contagious illnesses. Contact your doctor at once if you develop signs of infection.
Clolar can be harmful to the liver or kidneys, and these effects are increased when you also use other medicines that can harm the liver or kidneys. During your 5-day treatment with Clolar, you may need to avoid using certain medications. Discuss all treatment options with your doctor if you regularly use any other medications.
Tell your caregivers at once if you have a serious side effect such as rapid breathing and heart rate, trouble breathing, painful swelling, numbness or tingling, feeling like you might pass out, lower back pain, blood in your urine, urinating less than usual, or jaundice (yellowing of the skin or eyes).
Before receiving Clolar
If you have liver or kidney disease, you may need a dose adjustment or special tests to safely receive Clolar.FDA pregnancy category D. Clolar can cause harm to an unborn baby or cause birth defects. Before you receive this medicine, tell your doctor if you are pregnant. Use birth control to prevent pregnancy while you are receiving Clolar, whether you are a man or a woman. Clolar use by either parent may cause birth defects. It is not known whether clofarabine passes into breast milk or if it could harm a nursing baby. Do not breast-feed while you are receiving Clolar.
How is Clolar given?
Clolar is given as an injection through a needle placed into a vein. You will receive this injection in a clinic or hospital setting. The medicine must be given slowly through an IV infusion, and can take at least 2 hours to complete.
Clolar is usually given daily for 5 days in a row during one or more treatment cycles. Your doctor will determine how many treatment cycles you will receive and how often.
You may receive other medications to help prevent certain side effects of Clolar.
Clolar can lower the blood cells that help your body fight infections. This can make it easier for you to bleed from an injury or get sick from being around others who are ill.
To be sure your blood cells do not get too low, your blood will need to be tested on a regular basis. Your cancer treatments may be delayed based on the results of these tests. Your kidney or liver function may also need to be tested. Do not miss any follow-up visits to your doctor.
Contact your doctor at once if you develop signs of infection such as fever, chills, sore throat, flu symptoms, pale skin, easy bruising or bleeding (nosebleeds, bleeding gums), purple or red pinpoint spots under your skin, loss of appetite, mouth sores, or unusual weakness.
What should I avoid while receiving Clolar?
Avoid being near people who have colds, the flu, or other contagious illnesses. Contact your doctor at once if you develop signs of infection.
Clolar side effects
Get emergency medical help if you have any of these signs of an allergic reaction to Clolar: hives; difficult breathing; swelling of your face, lips, tongue, or throat. Tell your caregivers at once if you have a serious side effect such as:feeling like you might pass out;runny or stuffy nose, cough, rapid breathing and heart rate, trouble breathing, swelling and pain in any part of your body;lower back pain, blood in your urine, urinating less than usual or not at all;numbness or tingly feeling around your mouth;muscle weakness, tightness, or contraction, overactive reflexes;fast or slow heart rate, weak pulse, feeling short of breath, confusion, fainting;numbness or redness on the palms of your hands or the soles of your feet;jaundice (yellowing of the skin or eyes); or signs of infection such as fever, chills, sore throat, flu symptoms, pale skin, easy bruising or bleeding (nosebleeds, bleeding gums), purple or red pinpoint spots under your skin, loss of appetite, mouth sores, unusual weakness.

【原产地英文商品名】CLOLAR 1 MG/ML VIAL 1 X 20ML
【原产地英文药品名】CLOFARABINE
【中文参考商品译名】
以下是不同的规格和不同的价格，购买时请以电话咨询为准
·CLOLAR 1毫克/毫升 20毫升/支
·奈拉滨 250毫克/针剂 6针剂/盒
·克罗拉 4x20毫升瓶/盒
·克拉屈滨(LEUSTATIN仿制药)1毫克/毫升 10毫升/瓶 （产地：APP）

【中文参考药品译名】氯法拉滨
【生产厂家中文参考译名】GENZYME
【生产厂家英文名】GENZYME

部分中文 CLOLAR 处方信息
【化学名称】2-氯-9-(2-去氧-2-氟-β-D-阿拉伯呋喃)-9H-嘌呤-6-胺,2-chloro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purin-6-amine
【英文名称】Clofarabine
【药品名称】氯法拉滨
【又名】Clofarabine，Clolar，卢伐拉滨，克罗拉滨
美国Bioenvision公司开发, Genzyme公司生产，04.12.28FDA快速审评通道批准本品上市。现本品未申请进口，原料制剂均为3.1类。Bioenvision公司于2006年5月宣布，欧盟委员会已经批准其clofarabine（Evoltra）上市。用于治疗急性淋巴细胞性白血病。本品适用范围为复发的或对至少2种疗法无应答且没有其它疗法可选用的儿科急性淋巴细胞性白血病患者。此外，本品还可用于初次诊断为白血病的21岁及以下患者。
【药理作用】
Clofarabine 对不同的细胞株和肿瘤模型都表现出了很强的抗癌活性。早期的研究表明，本品的浓度在微摩尔以下就能有效地抑制人体CNS肿瘤、肺癌、肾癌、白血病细胞和黑色素瘤细胞系的增殖,体内和体外实验表明，clofarabine 对白血病细胞有细胞凋亡作用，此作用是通过下调BCL-2族蛋白BCL-X和MCL-1及AKT去磷作用实现的。其对人白血病细胞K-562的抑制作用比克拉屈滨和氟达屈滨更强，IC50为5nmol/L，而克拉屈滨的IC50是16nmol/L，氟达屈滨为460nmol/L。
临床前和合并用药实验表明，clofarabine和其它脱氧核苷酸类似物以及其他类型的抗癌药物如依托泊苷(etoposide)一样，能提高正常或异常的人体淋巴细胞中脱氧胞苷激酶的活性，因此能增加抗癌疗效。
在用异体移植的人结肠癌细胞株系进行的体内和体外研究中，clofarabine对肿瘤细胞系HCT116，HT-29，DLD-1和WiDr增殖的抑制作用比克拉屈滨和氟达屈滨更强，平均㏒IC50值分别是0.26，0.35和19umol/L。clofarabine口服给药比静脉注射给药更好，而且clofarabine的疗效随给药频率的增加而增加，在口服剂量为100mg/(kg·d)时，clofarabine就能完全抑制人体结肠肿瘤的肝转移。
给异体移植了人结肠肿瘤HT-9或人前列腺肿瘤PG3的胸腺机能缺乏的裸鼠连续9天单用clofarabine(2.5，5和10mg/kg，tid，ip)或与依立替康(irinotecan，CPT-11)或紫杉醇联合使用，结果表明，3个剂量的clofarabine对PG3均有疗效，而联合用药的疗效比单独用药好，可以明显降低用药的剂量，当clofarabine和紫杉醇的用量分别为2.5和1.25mg/kg时，就能明显延迟肿瘤细胞的生长，且毒性没有增加。
【药动学】
clofarabine被细胞中的脱氧胞苷激酶代谢为单、双和三磷酸盐的形式，在人类CLL细胞中，其单磷酸和三磷酸形式占大多数，具有活性的三磷酸代谢物达峰值时间为2小时，坪值在2～4小时。
用成年雄性SD大鼠进行的动物体内药代动力学研究表明，用药剂量与其消除速率有关，静脉注射10mg/kg的clofarabine后，药物的清除速度为2.1L/(h·kg)；而静脉注射25mg/kg后，清除速度降为1.5 L/(h·kg)，这可能是由于代谢饱和之故，药物在两种剂量下的t1/2分别是1.35和1.84h，分布容积分别为3.6L/kg(10mg)和3.2L/kg(25mg)。本品口服生物利用度在50%左右。
Clofarabine在鼠的离体肝组织中的消除速率较慢，首过代谢与克拉屈滨相似，大约为50%。本品从胆汁中以原形排泄的量小于剂量的1%。
【临床研究】
在一项临床研究中，有25位进行性白血病患儿，其中急性淋巴细胞白血病(ALL)17例和急性骨髓性白血病(AML)8例，接受了本品的治疗。病人每天静脉注射使用clofarabine，剂量为11.25～70mg/m2，1小时内滴完，一个疗程5天，根据病人的反应情况，每2～6周重复一个疗程。用药后的有效率为32%，5位患儿有所好转，3位部分好转，另有4位患儿的白血病细胞数量降低到足以允许进行骨髓移植的水平。实验的最大耐受剂量为52mg/(m2·d)，剂量限制性毒性是在70mg/(m2·d)剂量下出现可逆的肝毒性和皮肤疹。最常见的毒副作用是可逆的肝功能异常、恶心、呕吐、腹泻、黏膜炎、皮疹和肌痛等。
在另一项多中心、开标记的临床实验中，研究者以52mg/(m2·d)的剂量给ALL和AML患者静脉使用Clofarabine，每天1次，2小时内滴完，5天一个疗程，2～6周重复一次，结果有19位可评估的受试者，其中一位在用药后病情好转，5位部分好转，有效率为32%，另有5位患者的白血病细胞数量降低达到了允许进行骨髓移植的水平。与药物相关的毒性包括发热、中性白细胞减少、皮疹、恶心呕吐及短暂性的肝转氨酶含量升高。
经多项临床研究表明，Clofarabine对儿童急性淋巴细胞白血病和急性骨髓性白血病确有较好的疗效，可用于顽固性和复发性的ALL和AML，且耐受性良好。
【适应症】
　FDA批准的clofarabine的适应症为1-21岁复发性或顽固性急性淋巴细胞白血病，至少经过两个方案化疗而效果不理想者。
Clofarabine的优势及特点：
（1）结合了氟达拉滨（Fludarabine）和克拉屈滨（Cladribine） 的优点，既抑制DNA聚合酶，又抑制核糖核酸还原酶；
 (2)是目前唯一可以特异性用于儿童白血病的药物；
（3）治疗白血病有效率高。两次常规化疗无应答的患者, 对该药的总反应率为31%；
（4）病人耐受性好，无不可预知的不良反应；
 (5)具有潜在广谱抗肿瘤特性。
【适应症、用法用量】
用于1～21岁顽固性或复发性急性淋巴细胞白血病（ALL）患者，患者此前至少接受过2种优先使用的疗法。本品先用5％葡萄糖注射液或0.9％NaCl注射液稀释。儿童推荐剂量为52mg/m2，每天输注2小时，连续5天。器官功能回复到基线后，治疗周期循环，大约每2～6周一次。
本品结合了氟达拉滨和克拉屈滨 的优点，既抑制DNA聚合酶，又抑制核糖核酸还原酶，是目前唯一可以特异性用于儿童白血病的药物；治疗白血病有效率高。两次常规化疗无应答的患者, 对该药的总反应率为31%；病人耐受性好，无不可预知的不良反应；具有潜在广谱抗肿瘤特性。

Clofarabine 除了给患有ALL的儿童提供了一种很有价值的治疗方法外，对AML的治疗也具有实在的功效。在Ⅰ期试验中，16个患有AML的成人中有1个达到了完全缓解，8个患有AML的儿童中有1个达到了完全缓解。而更令人振奋的是在由患有AML成人参加的Ⅱ期试验。一个有31名患有复发性AML成人参加的试验中，8名初次缓解12个月或更长时间但复发的患者，经过clofarabine治疗后有6名获得了完全缓解；初次缓解12个月以内再次复发的11名患者，经过clofarabine治疗后有2名获得完全缓解；12名2次或多次复发的患者有5名获得完全缓解。另一项试验中，27名年龄60-79岁的新诊断AML，但不适合常规方案治疗的患者接受clofarabine治疗，有16名获得完全缓解，而其仅在3个患者身上表现出了3级毒性。在假定clofarabine 能调整阿糖胞嘧啶三磷酸盐在细胞内的蓄积，而且两者还没有重叠毒性的基础上，Faderl和他的同事在Ⅱ期成人试验中把clofarabine和阿糖胞嘧啶联合使用，并发现其对髓性白血病有很好的疗效和耐受性。由于clofarabine 能抑制DNA损伤的修复，因此正进行试验来测试clofarabine与DNA损伤剂联合使用的效果，例如拓扑异构酶Ⅱ抑制剂和烷化剂。总之，这些初步的研究结果促使对clofarabine 进行更进一步的研究以详细考察其在治疗急性白血病上的作用。
尽管儿童白血病的治愈率比较高，但是专门用于儿童的抗白血病药物还没有。成人用药用于儿童会带来很大的副作用、严重影响儿童的生活质量。Clofarabine作为第一个专门用于儿童白血病的药物，具有重大的意义。并且已经在美国获准快速审批。也证明了其潜在的临床价值。我国每年新增白血病患者4万人，其中一半是儿童。Clofarabine 的开发成功，不但能为广大患儿减少痛苦，也会给企业带来可观的经济效益。