拉帕替尼（lapatinib）——一种新的EGFR靶向治疗药物
乳腺癌晚期新药 Tykerb,是葛兰素史克公司研制的。 临床试验显示,对于那些已对罗氏的赫赛汀(Herceptin)产生耐药性的HER2型乳癌患者,这种新药有很好的临床效果
　拉帕替尼（lapatinib）是一种口服的小分子表皮生长因子（EGFR:ErbB-1，ErbB-2）酪氨酸激酶抑制剂。在体外试验中，对Her-2过表达乳腺癌细胞系的生长抑制作用明显。在Her-2过表达的进展期乳腺癌的Ⅰ期临床试验中，拉帕替尼（lapatinib）也具有较高的有效率，且与赫赛汀（曲妥珠单抗）无交叉耐药。因为其结构为小分子，与赫赛汀（曲妥珠单抗）不同，能够透过血脑屏障，对于乳腺癌脑转移有一定的治疗作用。

　Spector报告了拉帕替尼（lapatinib）单药（1500mg/d）在难治性炎性乳腺癌（曾用过蒽环类药物或复发）中的Ⅱ期临床结果。病人分为两组A组（ErbB-2过表达）和B组（ErbB-1表达，ErbB-2不表达）。A组使用拉帕替尼（lapatinib）的部分缓解率达62%，B组仅为8.3%。毒性反应主要表现为Ⅰ/Ⅱ级皮肤和胃肠道反应。这表明，拉帕替尼（lapatinib）疗效与HER-2过表达有密切关系。

   该药由葛兰素史克公司研制，是一种新型的靶向抗癌药物。所谓靶向治疗药物，是指将某些受体、基因或关键蛋白作为靶点，进而有的放矢地杀灭相关肿瘤细胞的药物。

   该药和另外一种乳腺癌治疗药物希罗达一起使用，可以有效控制晚期的转移性HER2阳性乳腺癌。两种药物联合用药疗法适用于那些之前服用过其他药物但治疗无效后乳腺癌转移的患者。

    拉帕替尼是一种激酶抑制剂，它的独特之处在于可以通过多种途径发挥作用，乳腺癌癌细胞不能接收到生长所需的信号。
拉帕替尼说明书

价格：250mg/150片/瓶， 32000元人民币
Company:

GlaxoSmithKline

Pharmacologic class:
Antineoplastic (tyrosine kinase inhibitor)

Active ingredient:
Lapatinib 250mg; tabs.

Indication:
In combination with capecitabine, for the treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab.

Pharmacology:
Overexpression of epidermal growth factor receptor (EGFR) and human epidermal receptor type 2 (HER2) has been reported in a variety of tumors. Lapatinib works by inhibiting the tyrosine kinase components of the EGFR and HER2 receptors.

Clinical trials:
Lapatinib was evaluated in combination with capecitabine in the treatment of breast cancer in a randomized, Phase 3 trial that enrolled 399 patients. The patients had HER2 overexpressing locally-advanced or metastatic breast cancer that had progressed following prior treatment with anthracyclines, taxanes, and trastuzumab. Capecitabine was given on Days 1?4 on a 21-day cycle, and lapatinib was given once daily continuously. The endpoint was time to progression (time from randomization to tumor progression or death due to breast cancer). An interim analysis revealed that, according to an independent assessment, the median time to progression in the group given lapatinib + capecitabine was 27.1 weeks compared to 18.6 weeks for capecitabine only. The response rate was 23.7% for the lapatinib + capecitabine group compared to 13.9% for the capecitabine-only group. Data results from investigator assessment was significant as well.

Adults:
Take 1 hour before or 1 hour after a meal. Take once daily on Days 1?1 continuously with capecitabine (see literature for capecitabine dose) in a repeating 21 day cycle. 1250mg (5 tablets). Severe hepatic dysfunction (Child-Pugh Class C): 750mg (no clinical data for this dose adjustment). After recovery from left ventricular ejection fraction (LVEF) decrease: 1g. Concomitant potent CYP3A4 inhibitors: 500mg (no clinical data for this dose adjustment). Concomitant potent CYP3A4 inducers: may titrate up to 4500mg (no clinical data for this dose adjustment). Discontinue if ≥Grade 2 NCI CTC toxicity occurs; may restart at 1250mg if toxicity improves to grade 1; if recurs, may restart at 1g.

Children:
Not recommended.

Contraindications:
Renal disease or dysfunction. Metabolic acidosis, ketoacidosis. Concomitant intravascular iodinated contrast agents (suspend during and for 48 hours after use). Type 1 diabetes.

Precautions:
Discontinue if ≥Grade 2 decrease in LVEF occurs, or if LVEF falls below institution抯 lower limit of normal; may restart after at least 2 weeks at reduced dose if asymptomatic and LVEF recovers. Conditions that impair left ventricular function, or risk factors for QT prolongation (eg, hypokalemia, hypomagnesemia, congenital long QT syndrome, concomitant antiarrhythmics, cumulative high dose anthracyclines); correct electrolyte disturbances before starting. Severe hepatic impairment. Pretreat for diarrhea with antimotility drugs. Monitor ECG. Pregnancy (Cat.D). Nursing mothers: not recommended.

Interactions:
Avoid potent CYP3A4 inhibitors (eg, ketoconazole), grapefruit; reduce dose if unavoidable. Avoid potent CYP3A4 inducers (eg, carbamazepine); slowly titrate dose up if unavoidable. May affect drugs that are affected by p-glycoprotein, CYP2C8.

Adverse reactions:
Diarrhea (may be severe), nausea, vomiting, hand/foot syndrome, rash, fatigue; decreased LVEF, QT prolongation.