TORISEL™ (temsirolimus) injection

TORISEL is the first mTOR inhibitor approved for the treatment of patients with advanced renal cell carcinoma (RCC). Learn more about the TORISEL mechanism of action. TORISEL provides significantly higher median overall survival and progression-free survival compared with interferon-alpha (IFN-α).1 Learn more about the efficacy of TORISEL. The TORISEL safety profile has been evaluated in clinical trials. Learn more about the adverse events profile of TORISEL in patients with advanced RCC. The recommended dose of TORISEL for advanced RCC is 25 mg infused over 30 to 60 minutes once weekly. Learn more about TORISEL dosage and administration. Important Safety Information
Hypersensitivity reactions manifested by symptoms, including, but not limited to anaphylaxis, dyspnea, flushing, and chest pain have been observed with TORISEL. Serum glucose, serum cholesterol, and triglycerides should be tested before and during treatment with TORISEL.
The use of TORISEL is likely to result in hyperglycemia and hyperlipemia. This may result in the need for an increase in the dose of, or initiation of, insulin and/or oral hypoglycemic agent therapy and/or lipid-lowering agents, respectively. The use of TORISEL may result in immunosuppression. Patients should be carefully observed for the occurrence of infections, including opportunistic infections. Cases of interstitial lung disease, some resulting in death, have occurred. Some patients were asymptomatic and others presented with symptoms. Some patients required discontinuation of TORISEL and/or treatment with corticosteroids and/or antibiotics. Cases of fatal bowel perforation occurred with TORISEL. These patients presented with fever, abdominal pain, metabolic acidosis, bloody stools, diarrhea, and/or acute abdomen. Cases of rapidly progressive and sometimes fatal acute renal failure not clearly related to disease progression occurred in patients who received TORISEL. Due to abnormal wound healing, use TORISEL with caution in the perioperative period. Patients with central nervous system tumors (primary CNS tumor or metastases) and/or receiving anticoagulation therapy may be at an increased risk of developing intracerebral bleeding (including fatal outcomes) while receiving TORISEL. Live vaccinations and close contact with those who received live vaccines should be avoided. Patients and their partners should be advised to avoid pregnancy throughout treatment and for 3 months after TORISEL therapy has stopped. The most common (incidence ≥30%) adverse reactions observed with TORISEL are: rash (47%), asthenia (51%), mucositis (41%), nausea (37%), edema (35%), and anorexia (32%). The most common laboratory abnormalities (incidence ≥30%) are anemia (94%), hyperglycemia (89%), hyperlipemia (87%), hypertriglyceridemia (83%), elevated alkaline phosphatase (68%), elevated serum creatinine (57%), lymphopenia (53%), hypophosphatemia (49%), thrombocytopenia (40%), elevated AST (38%), and leukopenia (32%). Most common grades 3/4 adverse events included asthenia (11%), dyspnea (9%), hemoglobin decreased (20%), lymphocytes decreased (16%), glucose increased (16%), phosphorus decreased (18%), and triglycerides increased (44%). Strong inducers of CYP3A4/5 (eg, dexamethasone, rifampin) and strong inhibitors of CYP3A4 (eg, ketoconazole, atazanavir) may decrease and increase concentrations of the major metabolite of TORISEL, respectively. If alternatives cannot be used, dose modifications of TORISEL are recommended. St. John’s Wort may decrease TORISEL plasma concentrations, and grapefruit juice may increase plasma concentrations of the major metabolite of TORISEL, and therefore both should be avoided. The combination of TORISEL and sunitinib resulted in dose-limiting toxicity.

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晚期肾癌的重磅靶向治疗药物Torisel (temsirolimus) 上市
转载自 中国癌症信息库 2008-01-27

简介：肾癌的重磅靶向治疗肾癌药物Torisel上市美国FDA已经批准Torisel（Temsirolimus）上市用于治疗进行性肾细胞癌（RCC）。Torisel是第一个治疗肾癌的靶向治疗药物，今年美国7月正式上市。肾细胞癌占全部肾肿瘤的85% ...

关键字：Torisel
 
美国FDA已经批准Torisel（Temsirolimus）上市用于治疗进行性肾细胞癌（RCC）。Torisel是第一个治疗肾癌的靶向治疗药物，今年美国7月正式上市。

肾细胞癌占全部肾肿瘤的85%。美国癌症协会预计今年将有新诊断肾癌51190例，其中40%在诊断时已经是晚期或发展阶段。Torisel是唯一上市的特异性抑制mTOR激酶的药物，mTOR激酶是调节细胞增值、生长和细胞存活重要的蛋白质。在体外研究中发现，Torisel抑制mTOR激酶后导致一定的血管生长因子如血管内皮生长因子的水平下降，进而阻止新生血管的发展。作为上市后安全监测措施，惠氏将提供2套完整的数据，其一已经完成，另一个关于肝细胞毒性的实验即将开始。Torisel也是目前唯一能够显著延长患者生存期的药物。惠氏为Torisel进行了包括626名患者的III期临床研究，共分为三组。Torisel单独一组，Torisel和alpha干扰素混合组以及alpha干扰素单独一组。结果显示，Torisel比alpha干扰素显著延长患者生存率达49%（10.9个月对7.3个月）；在次级评价指标上，Torisel比alpha干扰素显著延长患者的无进展（病情不进一步恶化）生存期（5.5个月对3.1个月）。Torisel和alpha干扰素组合使用没有显示更好的作用。

用法说明书

Company: Wyeth
Pharmacologic class: Antineoplastic (mTOR kinase inhibitor)

Active ingredient:
Temsirolimus 25mg/mL; ethanolic soln for IV infusion after two dilutions (first w. supplied diluent); contains alcohol, polysorbate 80.

Indication:
Advanced renal cell carcinoma.

Pharmacology:
Temsirolimus binds to an intracellular protein, and the resulting protein-drug complex inhibits the activity of an intracellular target called mTOR kinase, a cellular enzyme that regulates cell proliferation, cell growth and cell survival. In vitro studies show that inhibiting mTOR interferes with the translation of genes that regulate the cell cycle. It also resulted in reduced levels of certain cell growth factors involved in the development of new blood vessels, such as vascular endothelial growth factor.

Clinical trials:
In a study conducted in 626 previously untreated patients with advanced renal cell carcinoma, treatment with temsirolimus was compared to temsirolimus + interferon-α and to interferon-α alone. There was a statistically significant improvement in overall survival in the patients given temsirolimus (10.9 months) compared to those given interferon-α (7.3 months).

Adults:
25mg once weekly. Infuse IV over 30?0min, using an infusion pump. Continue until disease progression or unacceptable toxicity occurs. Premedicate with IV antihistamine (eg, diphenydramine). Hold dose if ANC <1000/mm3, platelets <75000/mm3, or NCI CTCAE ≥grade 3 adverse reaction occurs; may restart at a dose reduced by 5mg/week (no lower than 15mg/wk) if adverse reactions resolve to ≤grade 2. See Interactions.

Children:
Not recommended.

Precautions:
Sirolimus or related allergy. Hepatic insufficiency. Perioperative period (may interfere with wound healing). CNS tumors. Monitor CBCs weekly and chemistry panels every 2 weeks, blood glucose, lipids, renal function, and for worsening respiratory or GI symptoms (eg, acute abdomen, blood in stool). Elderly. Pregnancy (Cat.D) (avoid pregnancy during and for 3 months after therapy, male patients should use appropriate contraception), nursing mothers: not recommended.

Interactions:
Avoid strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice); if used, consider reducing temsirolimus dose to 12.5mg/week (allow 1 week after discontinuing CYP3A4 inhibitor before readjusting temsirolimus dose). Avoid strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifampicin, phenobarbital, St. John's Wort); if used, consider increasing temsirolimus dose to 50mg/week. Avoid live vaccines, close contact with vaccinees. Additive toxicity with sunitinib (rash, gout/cellulitis), anticoagulants (intracerebral bleeding).

Adverse reactions:
Rash, asthenia, mucositis, nausea, edema, anorexia, infection, pain, anemia, hyperglycemia, hyperlipemia, hypertriglyceridemia, elevated alkaline phosphatase, elevated serum creatinine, lymphopenia, hypophosphatemia, thrombocytopenia, elevated AST, leukopenia; hypersensitivity/infusion reactions (anaphylaxis, dyspnea, flushing, chest pain), immunosuppression, interstitial lung disease, bowel perforation, acute renal failure, abnormal wound healing; others (see literature).

How supplied:
Kit (vial + diluent)
TORISEL (TEMSIROLIMUS)25MG/ML+1.8ML DILU KIT

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