简介：阿斯利康的这个抗癌药物在美国和欧盟都获得了监管部门的批准。欧盟人用医药产品委员会(CHMP)推荐欧盟批准Caprelsa，而美国也在去年春季批准了这个药物。，这种新药是一种口服的激酶抑制剂，是第一个获批的治疗甲状腺髓样癌（medullary thyroid cancer，MTC）的有效的药物。
The European Commission has approved AstraZeneca’s thyroid cancer pill Caprelsa.
Advanced medullary thyroid cancer (MTC) is a rare type of the disease with a poor prognosis, and currently there are no approved therapies in Europe.
But whilst the drug was approved, there was one snag: Caprelsa may not be as beneficial in patients without, or are not known to have, a particular mutation - the Rearranged during Transfection (RET) mutation.
For patients in whom RET mutation is not known or is negative, a possible lower benefit should be taken into account before treatment, AZ said.
The firm added that its clinical data shows patients benefit from treatment with the drug regardless of their RET status.
But in line with Europe’s requirements, AZ said it would conduct a further study to confirm the benefits in patients who are RET-negative.
A pharmacovigilance plan for Caprelsa will also be implemented as part of the marketing authorisation, given its high number of common adverse events.
Caprelsa works as a once-daily oral treatment that uses two distinctive mechanisms of action.
The first is by blocking the blood supply to the tumour, by slowing the vascular endothelial growth factor receptor pathway and reducing the growth and survival of the tumour through epidermal growth factor receptor and RET pathways.
Vandetanib 100mg, 300mg, tabs.
Symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease.
Vandetanib inhibits the activity of tyrosine kinases, including those associated with epidermal growth factor receptor, vascular endothelial cell growth factor receptor, and protein tyrosine kinase 6. It has been shown to inhibit endothelial cell migration, proliferation, survival, and angiogenesis in vitro, and it inhibits the phosphorylation of tyrosine kinase. Vandetanib reduces tumor cell-induced angiogenesis, tumor vessel permeability, and inhibits tumor growth and metastasis in vivo in murine models.
A double-blind study involving 331 patients with unresectable locally advanced or medullary thyroid cancer was conducted to evaluate improvement in progression-free survival for vandetanib versus placebo. Overall survival and overall objective response rate were also examined. A statistically significant improvement in progression-free survival for patients randomized to vandetanib was demonstrated. At the time of primary analysis of progression-free survival, 15% of the patients had died, and there was no significant difference in overall survival between the two treatment groups. The overall objective response rate was 44% for those given vandetanib compared to 1% for placebo; all of the objective responses were partial responses.
Do not crush tabs. May disperse tabs in 2 ounces noncarbonated water for oral or NGT administration; avoid contact of dispersion with skin, mucous membranes. 300mg once daily. Renal impairment (CrCl<50mL/min): initially 200mg once daily. Reduce dose if severe toxicity or QTc interval prolongation occurs (see literature). Do not take a missed dose within 12hrs of the next dose.
Congenital long QT syndrome.
Hypocalcemia, hypokalemia, hypomagnesemia, QTcF interval >450msec, history of torsades de pointes, bradyarrhythmias, uncompensated heart failure, recent hemoptysis: not recommended. Ventricular arrhythmias. Recent MI. Monitor electrolytes (esp. K+, Ca++, Mg++), TSH, and ECG for QT prolongation at baseline, 2–4 weeks and 8–12 weeks after starting, then every 3 months, and after dose reductions or dose interruptions >2weeks; reduce dose as needed. Correct electrolyte disturbances before starting. Maintain serum K+ at least 4mEq/mL. Hepatic impairment (Child-Pugh B or C): not recommended. Suspend therapy and follow-up if dyspnea, cough, fever, QTcF >500msec, or posterior leukoencephalopathy symptoms (RPLS) occur. Avoid sun, UV light. Elderly. Pregnancy (Cat.D) (may cause fetal harm; use appropriate effective contraception during and for 4 months after stopping therapy), nursing mothers: not recommended.
Avoid strong CYP3A4 inducers (eg, carbamazepine, dexamethasone, phenytoin, phenobarbital, rifampin, rifabutin, rifapentine, St.John’s Wort). Avoid other drugs that can prolong QT interval (eg, amiodarone, disopyramide, procainamide, sotalol, dofetilide, chloroquine, clarithromycin, dolasetron, granisetron, haloperidol, pimozide, methadone, moxifloxacin).
Diarrhea (suspend if severe), rash, acne, nausea, hypertension, headache, fatigue, decreased appetite, abdominal pain, decreased calcium or glucose, increased ALT; QT prolongation, torsades de pointes, sudden death, severe skin reactions (eg, Stevens-Johnson syndrome; discontinue if occurs), interstitial lung disease, ischemic cerebrovascular events, hemorrhage, heart failure, hypothyroidism, hypertensive crisis, RPLS.
Prescribers and pharmacies must enroll in the Caprelsa REMS program by calling (800) 236-9933 or visit www.caprelsarems.com.
简介：药名：Caprelsa(凡德他尼vandetanib) 适应症：转移性甲状腺髓样癌 获批日期：4月6日 类型：小分子药物 简介：阿斯利康的这个抗癌药物在美国和欧盟都获得了监管部门的批准。欧盟人用医药产品委员会 ...