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美国FDA公布批准新赛诺菲-安万特(Sanofi-aventis)分子实体Jevtana(cabazitaxel)注射剂。
Manufacturer:
Sanofi-aventis
Pharmacological Class:
Antineoplastic (taxane antimicrotubule agent).
Active Ingredient(s):
Cabazitaxel 60mg/1.5mL; soln for IV infusion after dilution; contains polysorbate 80, diluent contains ethanol.
Indication(s):
In combination with prednisone, hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen.
Pharmacology:
Cabazitaxel is a semisynthetic taxane antineoplastic agent prepared from an extract of yew needles. Cabazitaxel is a microtubule inhibitor that binds to tubulin and promotes its assembly into microtubules while simultaneously inhibiting disassembly. This leads to the stabilization of microtubules, which results in the inhibition of mitotic and interphase cellular functions. It has been shown to have activity in tumor models that were insensitive to docetaxel chemotherapy as well as in those that were docetaxel-sensitive.
Cabazitaxel is extensively metabolized by the liver, and it is not recommended for use in patients with impaired hepatic function due to a probable increase in cabazitaxel levels and toxicity.
Clinical Trials:
Cabazitaxel was compared to mitoxantrone in a multicenter, randomized, open-label study in 755 patients with hormone-refractory metastatic prostate cancer previously treated with a docetaxel-containing regimen. Patients were randomized to receive either cabazitaxel (25mg/m2 every 3 weeks for up to 10 cycles with prednisone 10mg daily) or mitoxantrone (12mg/m2 every 3 weeks for up to 10 cycles with prednisone 10mg daily). Patients with hepatic impairment, hypertension, and certain cardiac conditions were excluded from the trial.
In an intent-to-treat analysis, the median survival time for the cabazitaxel group was 15.1 months, compared to 12.7 months for mitoxantrone; 61.9% of the patients in the cabazitaxel group died by the 30th month, compared to 74% in the mitoxantrone arm. The investigator-assessed tumor response was higher in the cabazitaxel group (14.4%) compared to the mitoxantrone group (4.4%).
Legal Classification:
Rx
Adults:
Pretreat with IV antihistamine, corticosteroid, and H2 blocker 30 min before each dose (see literature) and with antiemetic (IV or oral as needed). 25mg/m2 by IV infusion over 1 hour every 3 weeks, with oral prednisone 10mg/day during treatment. Do not treat if neutrophil count ≤1,500 cells/mm3. Prolonged grade ≥3 neutropenia (>1 week), febrile neutropenia, grade ≥3 diarrhea: delay treatment and/or reduce dose to 20mg/m2 (see literature). Discontinue if reactions persist after dosing at 20mg/m2.
Children:
Not recommended.
Contraindication(s):
Baseline neutrophil count ≤1,500cells/mm3. Allergy to polysorbate 80.
Warnings/Precautions:
Do CBC weekly in 1st cycle and before each subsequent cycle. Increased risk of neutropenia complications; consider G-CSF prophylaxis. Hepatic impairment: not recommended. Severe renal impairment (CrCl <30mL/min) or ESRD. Elderly (increased susceptibility to adverse reactions); monitor closely. Pregnancy (Cat.D; avoid). Nursing mothers: not recommended.
Interaction(s):
Avoid strong CYP3A4 inhibitors (eg, ketoconazole, clarithromycin, atazanavir, nefazodone, nelfinavir, ritonavir, saquinavir, voriconazole) (may potentiate cabazitaxel); caution with moderate CYP3A4 inhibitors. Avoid strong CYP3A4 inducers (eg, phenytoin, carbamazepine, rifampin, phenobarbital) (may antagonize cabazitaxel). Avoid St. John’s Wort.
Adverse Reaction(s):
Bone marrow suppression (esp. neutropenia, anemia, leukopenia, thrombocytopenia), febrile neutropenia, GI upset (esp. diarrhea, may be fatal), renal failure, fatigue, constipation, asthenia, abdominal pain, hematuria, back pain, anorexia, peripheral neuropathy, pyrexia, dyspnea, dysgeusia, cough, arthralgia, alopecia, hypersensitivity reactions (eg, rash, hypotension, bronchospasm).
How Supplied:
Kit (single-use vial + diluent)—1
Last Updated:
9/2/2010
制造商：
赛诺菲安万特
类药物：
抗肿瘤药（紫杉烷antimicrotubule剂）。
活性成分（S）：
Cabazitaxel 60mg/1.5mL;静脉输液稀释后soln;含有聚山梨酯80，稀释剂含有乙醇。
指示（S）：
结合强的松，激素难治性转移性前列腺癌的治疗与含多西他赛方案。
药理：
Cabazitaxel是一种半合成的紫杉烷类抗肿瘤药，从红豆杉针提取准备。 Cabazitaxel是一种微管抑制剂，以微管蛋白结合，并促进其装配成微管，同时抑制拆卸。这导致稳定的微管，抑制有丝分裂间期细胞功能的结果。它已被证明在多西紫杉醇化疗不敏感，以及那些被多西紫杉醇敏感的肿瘤模型的活动。
Cabazitaxel是由肝脏代谢，它不是在cabazitaxel水平和毒性可能增加，由于肝功能受损的患者使用的建议。
临床试验：
Cabazitaxel是比较米托蒽醌在一个多中心，随机，开放标签研究与激素难治性转移性前列腺癌患者在755以前处理与含多西他赛方案。患者被随机分配接受要么cabazitaxel（25mg/m2，每3周用强的松10mg，每日长达10个周期）或米托蒽醌（12mg/m2每日强的松10毫克，10个周期，每3周）。从试验肝功能损害，高血压和某些心脏疾病的患者被排除在外。
在一个意向性治疗分析，cabazitaxel组的平均存活时间为15.1个月，比为12.7个月对米托蒽醌; cabazitaxel组病人的61.9％，由30个月死亡，74％的米托蒽醌相比手臂。研究者评估肿瘤反应cabazitaxel组（14.4％）高于米托蒽醌组（4.4％）。
法律分类：
接收
成人：
四抗组胺药，皮质类固醇激素，H2受体阻滞剂30分钟前各剂量（见文献）预处理和止吐（IV或口服需要）。 25mg/m2静脉滴注1小时以上，每3周，治疗期间与口服强的松10mg/day。不要治疗，如果中性粒细胞计数≤1500 cells/mm3。长时间级≥3中性粒细胞减少（> 1周），发热性中性粒细胞减少，级≥3腹泻：延误治疗和/或减少剂量20mg/m2（见文献）。停止，如果反应后，在20mg/m2的剂量仍然存在。
儿童：
不推荐。
禁忌（S）：
基线中性粒细胞计数≤1500 cells/mm3。过敏聚山梨醇酯80。
警告/注意事项：
不要在第一个周期，每一个后续周期之前，加拿大广播公司每周。中性粒细胞减少并发症的风险增加;考虑G - CSF的预防措施。肝功能损害：不推荐。严重肾功能不全（肌酐清除率<30mL/min）或终末期肾病。长者（易感性增加不良反应）;密切监察。妊娠（Cat.D避免）。哺乳的母亲：不推荐。
相互作用（S）：
避免使用强效CYP3A4抑制剂（如酮康唑，克拉霉素，阿扎那韦，奈法唑酮，奈非那韦，利托那韦，沙奎那韦，伏立康唑）（可能与力量cabazitaxel）;中度CYP3A4抑制剂慎用。避免强CYP3A4诱导剂（如苯妥英钠，卡马西平，利福平，苯巴比妥）（可能拮抗cabazitaxel）。避免圣约翰草。
不良反应（S）：
骨髓抑制（尤其是中性粒细胞减少，贫血，白细胞减少，血小板减少），发热性中性粒细胞减少，胃肠不适（尤其是腹泻，可能是致命的），肾功能衰竭，乏力，便秘，乏力，腹痛，血尿，腰痛，食欲不振，外围神经病，发热，呼吸困难，味觉障碍，咳嗽，关节痛，脱发，过敏反应（如皮疹，低血压，支气管痉挛）。
如何提供：
试剂盒（单次使用小瓶+稀释剂）-1
最后更新：
2011年8月12日
美FDA批准卡巴他赛二线治疗转移性激素不应性前列腺癌
2010年6月,美国FDA经优先审批程序批准了Sanofi-Aventis公司开发的卡巴他赛注射剂（cabazitaxel/Jevtana）,用于联合泼尼松（prednisone）治疗既往已接受过一种含多西他赛（docetaxel/Taxotere）治疗方案治疗的转移性激素不应性前列腺癌患者。
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