10月21日消息 - 美国FDA10月19日批准葛兰素史克生产的Votrient为治疗晚期肾细胞癌的新型药物，Votrient为自2005年以来FDA批准的第6个治疗肾细胞癌的药物。

    Votrient是一种新型口服血管抑制药，它通过干扰实体瘤生长和生存所需要的新生血管的发生而达到抗癌的目的。

    2009年，近49000个人被诊断为肾细胞癌，11000个死于肾细胞癌。

    FDA药物评价和研究中心，抗肿瘤药部门主管Richard Pazdur博士说：“2005年以前，可供选择的有效的治疗肾细胞癌的方法非常有限，而现在，通过治疗病人五年生存率大大提高”。

    Votrien的有效性和安全性通过监测435个病人的疾病无恶化生存期得到证实。通过随访参与研究的肿瘤再次生长或者死亡之前的前列腺癌症患者，结果发现，接受Votrien治疗的患者的平均疾病无恶化的生存期为9.2个月，而对照组为4.2个月。

    不良反应包括：腹泻、高血压、发色改变、恶心、无食欲、呕吐、疲乏、虚弱、腹痛和头疼。Votrien还能引起严重的甚者致死性的肝毒性，故治疗前和治疗期间内应监测血压和肝功能。Votrien对胎儿有害，怀孕期间禁止使用。

    Votrien还能导致心律失常，服药期间，应该定期做心电图监测心律，定期做血检以监测电解质失衡引起的心率失常。

VOTRIENT

Indication(s):

Advanced renal cell carcinoma.

Pharmacology:

Pazopanib is a multi-kinase inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, platelet-derived growth factor receptor-α and-β, fibroblast growth factor receptor-1, and -3, cytokine receptor, interleukin-2 receptor inducible T-cell kinase, leukocyte-specific protein tyrosine kinase, and transmembrane glycoprotein receptor tyrosine kinase.

Clinical Trials:

Pazopanib was evaluated in a placebo-controlled Phase 3 study involving 435 patients with renal cell carcinoma. Patients were randomized (2:1) to receive pazopanib 800mg or placebo once daily. In this trial, the overall median progression free survival (PFS) was 9.2 months with pazopanib and 4.2 months with placebo. Treatment-naive patients who received pazopanib experienced 11.1 months of median PFS vs 2.8 months with placebo. Additionally, patients who had previously received cytokine-based treatment achieved 7.4 months of median PFS with pazopanib vs 4.2 months with placebo.

Legal Classification:

Rx

Adults:

Take on an empty stomach. Swallow whole. 800mg once daily. Hepatic impairment: moderate: 200mg once daily; severe: not recommended. Concomitant strong CYP3A4 inhibitors (eg, ketoconazole, ritonavir, clarithromycin): avoid; if warranted, reduce dose of pazopanib to 400mg; may reduce further if toxicity occurs. Concomitant strong CYP3A4 inducers (eg, rifampin): avoid.

Children:

Not recommended.

Precaution(s):

Monitor liver tests before starting and at least once every 4 weeks for at least the first 4 months of treatment, then periodically. If ALT between 3xULN and 8xULN continue therapy with weekly monitoring until ALT returns to Grade 1 or baseline. If ALT >8xULN interrupt therapy until ALT returns to Grade 1 or baseline; may consider reintroducing at a reduced dose, measure liver tests weekly for 8 weeks; if ALT>3xULN recurs, permanently discontinue. Permanently discontinue if ALT>3xULN and bilirubin >2xULN. Gilbert’s syndrome (see literature). History of QT prolongation. Cardiac disease. Monitor ECG, electrolytes (eg, calcium, magnesium, potassium), thyroid, urinalysis. History of hemoptysis, cerebral, or clinically significant GI hemorrhage in the past 6 months: not recommended. Risk of arterial thrombotic events (within previous 6 months: not recommended). Discontinue if severe and persistent hypertension (despite antihypertensive therapy and dose reduction) or if Grade 4 proteinuria occurs. Stop therapy at least 7 days before surgery; discontinue in patients with wound dehiscence. Pregnancy (Cat.D), nursing mothers: not recommended.

Interaction(s):

See Adult dosing: Potentiated by strong CYP3A4 inhibitors, grapefruit juice. Antagonized by strong CYP3A4 inducers. Concomitant drugs with narrow therapeutic windows metabolized by CYP3A4, CYP2D6, or CYP2C8: not recommended. Caution with concomitant drugs that prolong QT interval (eg, antiarrhythmics).

Adverse Reaction(s):

Diarrhea, hypertension, hair color changes, nausea, anorexia, vomiting; hepatotoxicity (may be severe or fatal), QT prolongation, hemorrhagic events, arterial thrombotic events (eg, MI, angina, ischemic stroke, TIA), GI perforation or fistula, impaired wound healing, hypothyroidism, proteinuria.

How Supplied:

Tabs 200mg—30, 90, 120
400mg—30, 60

Last Updated:

2/3/2010