中文名称 伊沙匹隆
英文名称 Ixabepilone
英文别名 (1R,5S,6S,7R,10S,14S,16S)-6,10-Dihydroxy-1,5,7,9,9-pentamethyl-14-[(E)-1-(2-methyl-1,3-thiazol-4-yl)prop-1-en-2-yl]-17-oxa-13-azabicyclo[14.1.0]heptadecane-8,12-dione; (1S,3S,7S,10R,11S,12S,16R)-7,11-dihydroxy-8,8,10,12,16-pentamethyl-3-[(E)-1-methyl-2-(2-methyl-1,3-thiazol-4-yl)ethenyl]-17-oxa-4-azabicyclo[14.1.0]heptadecane-5,9-dione
CAS号 219989-84-1
分子式 C27H42N2O5S
分子量 506.6978
InChI InChI=1/C27H42N2O5S/c1-15-9-8-10-27(7)22(34-27)12-20(16(2)11-19-14-35-18(4)28-19)29-23(31)13-21(30)26(5,6)25(33)17(3)24(15)32/h11,14-15,17,20-22,24,30,32H,8-10,12-13H2,1-7H3,(H,29,31)/b16-11+/t15-,17+,20-,21-,22-,24-,27+/m0/s1
分子结构 

密度 1.122g/cm3
适应症：用于治疗乳腺癌。
规格：
IXEMPRA INJ 15MG KIT
IXEMPRA INJ 45MG KIT
剂型：注射剂

美国FDA批准百时美施贵宝公司的埃博霉素（epothilone）B半合成同系物伊沙匹隆注射剂（ixabepilone，Ixempra）上市，单一用药治疗对蒽环类、紫杉醇类和卡培他滨等药物产生抗药性的转移性或晚期局部乳腺癌患者。美国FDA还批准伊沙匹隆与卡培他滨联合用药治疗对蒽环类、紫杉醇类药物或肿瘤抗紫杉醇类药物产生抗药性而再用蒽环类药物治疗有禁忌的转移性或晚期局部乳腺癌患者。依扎匹隆属埃博霉素等微管抑制剂类抗肿瘤药。本品剂量规格：伊沙匹隆15mg/瓶和稀释剂8mL/瓶；伊沙匹隆45mg/瓶和稀释剂23.5 mL/瓶。
美国FDA批准本品是基于2项们纳入878例患者的国际性多中心临床研究和其单一用药治疗或与卡培他滨联合用药治疗转移性或晚期局部乳腺癌患者的疗效和安全性结果。
随机Ⅲ期临床研究评价了伊沙匹隆和卡培他滨联合用药与卡培他滨治疗单一用药的比较。752例患者先前接受过蒽环类和紫杉醇类药物治疗，显示肿瘤对这些治疗有抗药性。在主要研究终点，伊沙匹隆/卡培他滨联合用药组较单一卡培他滨组在统计学上显著延长病情不加重的患者存活期：平均5.7月（95% CI，4.8-6.7）对4.1月（95% CI，3.1-4.3）；危险比＝0.69（95% CI，0.58-0.83）。

Ixempra Generic Name: Ixabepilone (ix-ab-EP-i-lone)Brand Name: Ixempra
Do not take Ixempra if you also take capecitabine and you have high liver enzyme levels. It may increase your risk for toxicity and death caused by low white blood cell levels. Tell your doctor before you use Ixempra if you have liver problems.
Ixempra is used for:
Treating breast cancer. It may be used alone or with other medicines. It may also be used for other conditions as determined by your doctor.

Ixempra is a microtubule inhibitor. It works by blocking cancer cell growth and reproduction.

Do NOT use Ixempra if:
you are allergic to any ingredient in Ixempra
you have had a severe allergic reaction to products that contain Cremophor EL or castor oil
you have low white blood cell or platelet levels
you have high liver enzyme levels and you also take capecitabine
you are taking certain cephalosporins (eg, cefotetan), disulfiram, or metronidazole
Contact your doctor or health care provider right away if any of these apply to you.

Before using Ixempra :
Some medical conditions may interact with Ixempra . Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding
if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
if you have allergies to medicines, foods, or other substances
if you have a history of heart problems (eg, irregular heartbeat, heart attack), diabetes, liver problems, nerve problems, or bone marrow problems
if you have an infection, high liver enzyme levels, or blood problems (eg, low white blood cell or platelet levels)
Some MEDICINES MAY INTERACT with Ixempra . Tell your health care provider if you are taking any other medicines, especially any of the following:

Certain cephalosporins (eg, cefotetan), disulfiram, furazolidone, metronidazole, or sulfonylureas (eg, glyburide) because a reaction including flushing, headache, fast or irregular heartbeat, difficult or fast breathing, nausea, vomiting, or dizziness may occur
Azole antifungals (eg, ketoconazole), delavirdine, fluconazole, HIV protease inhibitors (eg, ritonavir), macrolide antibiotics (eg, clarithromycin), nefazodone, telithromycin, trazodone, verapamil, or voriconazole because they may increase the risk of Ixempra 's side effects
Barbiturates (eg, phenobarbital), carbamazepine, dexamethasone, efavirenz, hydantoins (eg, phenytoin), rifabutin, rifampin, or St. John's wort because they may decrease Ixempra 's effectiveness
This may not be a complete list of all interactions that may occur. Ask your health care provider if Ixempra may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Ixempra :
Use Ixempra as directed by your doctor. Check the label on the medicine for exact dosing instructions.

An extra patient leaflet is available with Ixempra . Talk to your pharmacist if you have questions about this information.
Ixempra is usually given once every 3 weeks. It is given as an injection at your doctor's office, hospital, or clinic.
You will receive other medicines about 1 hour before each treatment with Ixempra to decrease the chance of an allergic reaction. Discuss any questions with your doctor.
If vomiting or diarrhea occurs, you will need to take care not to become dehydrated. Contact your doctor for instructions.
Do not eat grapefruit or drink grapefruit juice while you are using Ixempra .
If you miss a dose of Ixempra , contact your doctor right away.
Ask your health care provider any questions you may have about how to use Ixempra .

Important safety information:
Ixempra may cause drowsiness or dizziness. These effects may be worse if you take it with alcohol or certain medicines. Use Ixempra with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.
Ixempra has alcohol in it. It may interact with certain other medicines (eg, certain cephalosporins, disulfiram, furazolidone, metronidazole, sulfonylureas). It may also increase the effects of alcohol in drinks or other medicines. Before you start any new medicine, check the label to see if it has alcohol in it too. If it does or if you are not sure, check with your doctor or pharmacist.
Ixempra may lower the ability of your body to fight infection. Avoid contact with people who have colds or infections. Tell your doctor if you notice signs of infection like fever, sore throat, rash, or chills.
Ixempra may reduce the number of clot-forming cells (platelets) in your blood. Avoid activities that may cause bruising or injury. Tell your doctor if you have unusual bruising or bleeding. Tell your doctor if you have dark, tarry, or bloody stools.
Check with your doctor before you receive any vaccine while you are using Ixempra .
Tell your doctor or dentist that you take Ixempra before you receive any medical or dental care, emergency care, or surgery.
Women who are able to become pregnant should use an effective form of birth control (eg, condoms) while using Ixempra . Ask your doctor any questions you may have about effective birth control.
Lab tests, including complete blood counts and liver function, may be performed while you use Ixempra . These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.
Use Ixempra with caution in the ELDERLY; they may be more sensitive to its effects.
Ixempra should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed.
PREGNANCY and BREAST-FEEDING: Ixempra has been shown to cause harm to the fetus. Do not become pregnant while you are using it. If you think you may be pregnant, contact your doctor. You will need to discuss the benefits and risks of using Ixempra while you are pregnant. It is not known if Ixempra is found in breast milk. Do not breast-feed while using Ixempra .
Possible side effects of Ixempra :
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; diarrhea; dizziness; fingernail or toenail changes; hair loss; headache; hot flashes; loss of appetite; mild joint or muscle pain; mild weight loss; nausea; mouth sores; stomach pain or upset; taste changes; tiredness or weakness; trouble sleeping; or vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:
Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain or tightness; difficult or painful urination; fainting; irregular heartbeat; numbness, tingling, or burning of the hands or feet; pain, swelling, redness, or blistering at the injection site; redness, tenderness, or dryness of the palms of hands or soles of feet; severe or persistent dizziness; severe or persistent nausea, vomiting, or diarrhea; severe tiredness or weakness; shortness of breath; signs of an infection (eg, fever, chills, cough, sore throat); swelling of arms, hands, legs, or feet; unusual bruising or bleeding; unusual weight gain.

美国FDA批准Ixempra（伊沙匹隆注射剂)上市

Ixempra（Ixabepilone，伊沙匹隆）是一种类似紫杉醇微管蛋白聚合和抑制微管解聚活性的埃坡霉素(epothilones)类抗肿瘤化疗新药，由施贵宝公司研发生产。2007年10月FDA批准Ixempra单药或与卡培他滨联用用于治疗蒽环类、紫杉烷衍生物和卡培他滨治疗无效的转移性或局部进展的晚期乳腺癌。埃坡霉素(epothilones)：是一类十六元环的大环内酯类药物，最早由Holfe和Reichenbach两人在1992年从粘细菌Sorangium cellulosum种中分离得到，Ixabepilone（BMS-247550）是半合成epothilone β内酰胺类似物，属于新一代抗有丝分裂药物，其作用机制与紫杉醇类药物（taxanes）类似，可与微管蛋白结合导致癌细胞无法顺利进行有丝分裂，进而使癌细胞产生凋亡，在抗肿瘤谱、抗肿瘤活性、安全性、水溶性及合成方法等方面均优于紫杉醇。
Ixempra是第一个埃博霉素类全新抗肿瘤药物，可与微管蛋白结合而导致癌细胞不能顺利进行有丝分裂，最终使肿瘤细胞凋亡。Ixempra具有全新的化学结构，与紫杉类具有不同的微管结合位点，因此具有更强的抗肿瘤活性。而且，Ixempra对肿瘤耐药机制易感性低。
Ixempra单药治疗
在Ixempra单药治疗蒽环类、紫杉类和卡培他滨耐药转移性乳腺癌的Ⅱ期临床试验中，乳腺癌患者静脉输注Ixempra 40mg/m23小时，每3周1个疗程，直至疾病进展（PD）。结果显示，在113例可评估患者中，ORR为11.5%，疾病稳定（SD）率为50.0%，中位无进展生存期（PFS）为3.1个月。在3～4级毒性反应中以中性粒细胞减少发生率最高（54%），其他还可见外周神经毒性、虚弱、肌痛、黏膜炎等。
Ixempra联合治疗
CA163046研究是一项随机Ⅲ期临床试验。该研究纳入了752例对蒽环类和紫杉类耐药的转移性或局部晚期乳腺癌患者。患者被随机分为联合治疗组（n=375）和单药治疗组（n=377），分别接受Ixempra（40mg/m2，静脉输注>3小时，d1，q3w）+卡倍他滨（每日2000mg/m2，分2次口服，d1～d14，q3w）或卡倍他滨单药治疗（每日2500mg/m2，分2次口服，d1～d14，q3w）。研究者对既往治疗耐药进行了严格定义：接受蒽环类和紫杉类辅助化疗或转移性疾病治疗后肿瘤快速进展的转移性乳腺癌。该研究的主要终点为PFS[采用盲法独立放射影像学评估（IRR）]；次要终点为ORR、至缓解时间、缓解持续时间和总生存期（OS）。
结果显示，两组患者年龄、KPS评分、既往接受过转移性疾病治疗方案、既往接受过的治疗等基线特征相似，具有可比性。此外，两组患者的病灶数、内脏转移情况、激素受体状态、Her-2状态等疾病和肿瘤特征也相似。基于IRR评估，两组ORR分别为35%和14%（P<0.0001），而联合和单药治疗组患者的中位PFS分别为5.8个月和4.2个月（HR：0.75，P=0.0003）。
亚组分析证实，相比卡培他滨单药治疗，Ixempra联合卡培他滨在各个治疗亚组均显示出PFS的益处。进一步亚组分析（55例）表明，Ixempra联合卡培他滨一线治疗耐药转移性乳腺癌较卡培他滨单药治疗显著改善了患者的PFS（7.0个月对2.1个月；HR：0.46，P=0.0109）。
联合治疗组发生3～4度血液学毒性的比例高于单药治疗组，主要包括白细胞减少（57%对6%）、中性粒细胞减少（68%对11%）、贫血（10%对4%）、血小板减少（8%对4%）和中性粒细胞减少伴发热（4%对<1%）。联合治疗组较单药治疗组多见的3～4度非血液学毒性包括外周神经病变（主要为感觉神经病变，属于累积毒性，可逆，恢复至基线状态或1度的中位时间为6周）、乏力、肌痛、黏膜炎、关节痛等，单药组腹泻发生率则多于联合治疗组。
研究证实，对于蒽环类和紫杉类耐药的转移性乳腺癌，Ixempra联合卡倍他滨的疗效优于卡倍他滨单药治疗：延长PFS（HR：0.75），提高ORR2.5倍（35%对14%），且各亚组患者均显示出生存获益。Ixempra联合卡培他滨治疗组的血液学毒性发生率较高，神经病变（微管稳定药物已知的毒性）属于累积毒性，可逆。Ixempra联合卡培他滨是蒽环类和紫杉类耐药转移性乳腺癌的有效治疗选择。