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药品信息:
Bosutinib-新的化疗药物对白血病和其他癌症
Bosulif Approved for Previously Treated Philadelphia Chromosome-Positive Chronic Myelogenous Leukemia
Pfizer announced that the FDA has approved Bosulif (bosutinib) for the treatment of adult patients with chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance, or intolerance to prior therapy.
The registrational trial (Study 200) was a global, single-arm, open-label, multi-cohort, Phase 1/2 study of >500 patients with imatinib (Gleevec; Novartis)-resistant or –intolerant Ph+ CML with separate cohorts for chronic, accelerated and blast phase disease previously treated with one prior TKI (imatinib) or more than one TKI (imatinib followed by dasatinib [Sprycel; Bristol-Myers Squibb] and/or nilotinib [Tasigna; Novartis]).
The major cytogenetic response (MCyR) at 24 weeks for patients with chronic phase CML who had been previously treated with imatinib only (n=266) was 33.8% (95% CI: 28.2, 39.9). With a minimum follow-up of 23 months, 53.4% of patients achieved a MCyR. Of patients who achieved MCyR, 52.8% had a MCyR lasting at least 18 months. The median duration of MCyR was not reached for these patients.
The MCyR by 24 weeks for patients with chronic phase CML who had been treated with imatinib and at least one other TKI (n=108) was 26.9% (95% CI: 18.8, 36.2). With a minimum follow-up of 13 months, 32.4% of patients achieved a MCyR. Of patients who achieved MCyR, 51.4% had a MCyR lasting at least nine months. The median duration of MCyR was not reached for these patients.
A low rate of transformation (4%, n=16) from the chronic phase to the advanced or blast phase was also observed in patients treated with Bosulif.
Bosulif is a kinase inhibitor that limits cancer cell growth by inhibiting the Abl and Src signaling pathways. Bosulif is expected to be available mid-September. It will be available as 100mg and 500mg tablets.
产品名称：伯舒替尼,博舒替尼
中文别名:博舒替尼; 4-[(2,4-二氯-5-甲氧基苯基)氨基]-6-甲氧基-7-[3-(4-甲基-1-哌嗪)丙氧基]-3-喹啉甲腈
质量标准：含量> 99%
本品由美国惠氏制药公司（Wyeth Pharmaceuticals）研制，是一种强效的蛋白激酶Src/Ab1双重抑制剂。
药理作用：博舒替尼(Bosutinib，SKI 606)，由惠氏制药(Wyeth)开发，是SRC和BCR ABL双重抑制剂，该化合物对血小板源性生长因子的酪氨酸激酶没有活性，但能抑制BCR ABL和LYN(一个芽殖期的内褶蛋白质)转磷酸化和细胞增殖作用。伯舒替尼对Y253H、E255V、E255K和F359V突变的BCR ABL有效，在小鼠实验中显示出有抑制K562异种移植物增生的作用，但对T315I突变依然没有效果。在Ⅰ-Ⅱ期临床研究中，69位伊马替尼耐药的CML或ph+ALL病人用伯舒替尼后症状都得到了好转，其副作用有腹泻、恶心和呕吐等。
储存条件：2-8摄氏度，避光防潮密闭干燥
包装规格：10mg 200mg 1g 500mg
Pharmacological Class:
Tyrosine kinase inhibitor.
Active Ingredient(s):
Bosutinib 100mg, 500mg; tablets.
Company
Pfizer Inc.
Indication(s):
Treatment of chronic, accelerated, or blast phase Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML) with resistance or intolerance to prior therapy.
Pharmacology:
Bosutinib is a tyrosine kinase inhibitor. It inhibits the Bcr-Abl kinase that promotes CML; it is also an inhibitor of Src-family kinases including Src, Lyn, and Hck. Bosutinib inhibited 16 of 18 imatinib-resistant forms of Bcr-Abl expressed in murine myeloid cell lines. Bosutinib did not inhibit the T315I and V299L mutant cells.
Clinical Trials:
A single-arm, Phase 1/2 open-label, multicenter trial was conducted to evaluate the efficacy and safety of bosutinib 500mg once daily in patients with imatinib-resistant or -intolerant CML with separate cohorts for chronic, accelerated, and blast phase disease previously treated with one prior TKI (imatinib) or more than one TKI (imatinib followed by dasatinib and/or nilotinib). The trial enrolled 546 patients with CP, AP or BP CML.
The efficacy endpoints for patients with CP CML previously treated with imatinib were the rate of attaining MCyR at week 24 and the duration of MCyR. The efficacy endpoints for patients with CP CML previously treated with both imatinib and at least 1 additional TKI were the cumulative rate of attaining MCyR by week 24 and the duration of MCyR. In patients with CP CML with prior treatment with only imatinib, 33.8% achieved an MCyR at week 24 and, with a minimum follow-up of 23 months, 53.4% achieved an MCyR. In patients with CP CML with prior treatment with imatinib and dasatinib and/or nilotinib, 26.9% achieved an MCyR by week 24 and, with a minimum follow-up of 13 months, 32.4% achieved an MCyR.
The efficacy endpoints for patients with previously treated AP and BP CML were confirmed complete hematologic response (CHR) and overall hematologic response (OHR). By Week 48, 30.4% of patients with AP CML attained CHR; 55.1% attained OHR. Also, 15% of patients with BP CML attained CHR; 28.3% attained OHR.
Legal Classification:
Rx
Adults:
500mg once daily with food. Continue until disease progression or patient intolerance. Consider dose escalation to 600mg once daily in patients who do not reach complete hematological response (CHR) by week 8 or a complete cytogenetic -response (CCyR) by week 12, who did not have Grade 3 or higher adverse reactions. Adjust dose for hematologic and non-hematologic toxicity: see literature. Hepatic impairment: 200mg daily.
Children:
<18 years: not established.
Warnings/Precautions:
Monitor and manage GI toxicity, fluid retention; withhold, reduce dose, or discontinue as necessary. Perform CBC weekly for first month, then monthly; hepatic enzyme tests monthly for first three months (more frequently if transaminase elevations occur); withhold, reduce dose, or discontinue as necessary. Pregnancy (Category D), nursing mothers: not recommended.
Interaction(s)
Potentiated by concomitant strong or moderate CYP3A and/or P-gp inhibitors (eg, ritonavir, indinavir, nelfinavir, saquinavir, ketoconazole, boceprevir, telaprevir, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin, nefazodone, conivaptan, fluconazole, darunavir, erythromycin, diltiazem, atazanavir, aprepitant, amprenavir, fosamprenavir, crizotinib, imatinib, verapamil, grapefruit products, ciprofloxacin); avoid. Antagonized by concomitant strong or moderate CYP3A inducers (eg, rifampin, phenytoin, carbamazepine, St. John’s Wort, rifabutin, phenobarbital, bosentan, nafcillin, efavirenz, modafinil etravirine); avoid. Antagonized by proton pump inhibitors (eg, lansoprazole); consider short-acting antacids or H2 blockers instead; separate dosing by more than 2 hours. May potentiate drugs that are P-gp substrates (eg, digoxin).
Adverse Reaction(s)
Diarrhea, nausea, thrombocytopenia, vomiting, abdominal pain, rash, anemia, pyrexia, fatigue; fluid retention (monitor), hepatic toxicity.
How Supplied:
Tabs 100mg—120; 500mg—30
LAST UPDATED:
11/12/2012
治疗慢性髓性白血病新药—伯舒替尼（bosutinib）
美国食品与药物管理局（FDA）于2012年9月4日批准了新的“孤儿药”伯舒替尼（bosutinib）用于治疗慢性髓性白血病（CML），后者以老年人发病居多。
伯舒替尼预期用于对其他治疗包括伊马替尼（imatinib）治疗不耐受或有抵抗的慢性期、加速期或急变期Ph染色体阳性的CML患者。
大多数CML患者有基因突变，可见费城（Ph）染色体，该染色体可导致骨髓产生酪氨酸激酶，后者启动大量异常粒细胞增殖。伯舒替尼通过阻断酪氨酸激酶信号而发挥作用。
伯舒替尼的安全性和有效性在一项纳入546例成人慢性髓性白血病患者的临床试验中得到了证实。
接受伯舒替尼治疗的患者最常见不良反应包括腹痛、腹泻，恶心、呕吐，血小板减少，皮疹，贫血，发热和疲劳。
FDA批准的治疗慢性髓性白血病其他药物包括伊马替尼（2001），达沙替尼（dasatinib，2006）和尼洛替尼（nilotinib，2007）。
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产地国家: 美国
原产地英文商品名:
Bosutinib 50mg
原产地英文药品名:
Anti-Cancer
中文参考商品译名:
博舒替尼 500毫克
生产厂家中文参考译名:
美国惠氏制药公司
生产厂家英文名:
Wyeth Pharmaceuticals
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产地国家: 美国
原产地英文商品名:
Bosutinib 200mg
原产地英文药品名:
Anti-Cancer
中文参考商品译名:
博舒替尼 200毫克
生产厂家中文参考译名:
美国惠氏制药公司
生产厂家英文名:
Wyeth Pharmaceuticals
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产地国家: 美国
原产地英文商品名:
Bosutinib 1g
原产地英文药品名:
Anti-Cancer
中文参考商品译名:
博舒替尼 1克
计价单位: 包
生产厂家中文参考译名:
美国惠氏制药公司
生产厂家英文名:
Wyeth Pharmaceuticals
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产地国家: 美国
原产地英文商品名:
Bosutinib 10mg
原产地英文药品名:
Anti-Cancer
中文参考商品译名:
博舒替尼 10毫克
计价单位: 包
生产厂家中文参考译名:
美国惠氏制药公司
生产厂家英文名:
Wyeth Pharmaceuticals
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临床试验期:
中文适应病症参考翻译1:
白血病
中文适应病症参考翻译2:
乳腺癌
中文适应病症参考翻译3:
肿瘤 | 
