School of Pharmacy, University of Wisconsin-Madison, Madison. WI, USA.
Am J Health Syst Pharm. 2013 Jun 15;70(12):1033-8. doi: 10.2146/ajhp120311.
The pharmacology, clinical efficacy, adverse effects, cost, and place in therapy of vismodegib are reviewed.
Vismodegib, the first oral treatment for basal cell carcinoma (BCC), was recently approved for the treatment of patients with locally advanced or metastatic BCC whose cancer is refractory to standard treatments or who are not candidates for surgery or radiation. Vismodegib is a small molecule that potently inhibits signal transduction in the hedgehog signaling pathway, demonstrates nonlinear pharmacokinetics, and has a half-life of 13 days. Agents that increase gastrointestinal pH may reduce the solubility and bioavailability of vismodegib. It is effective in both locally advanced and metastatic BCCs, with response rates ranging from 30% to 60% in two clinical trials. Vismodegib is available as a 150-mg capsule, and the approved dosage is 150 mg orally once daily. The most common adverse effects of vismodegib include mild-to-moderate hair loss, muscle cramps, taste disturbance, and weight loss. The estimated cost of one month of treatment with vismodegib is $7500.
Vismodegib was recently approved for the treatment of locally advanced or metastatic BCC that is refractory to standard treatments or if patients are not candidates for surgery or radiation. Vismodegib may have little effect on the treatment of BCC, given its high cost, the high cure rates achieved with standard therapies, and its unacceptable toxicity profile in patients with a non-life-threatening disease. However, vismodegib's novel mechanism of action, oral dosage form, preliminary efficacy, and tolerability compared with cytotoxic chemotherapy may make it an attractive candidate for the treatment of other cancers.
本文综述了维莫德吉的药理学、临床疗效、不良反应、成本和治疗地位。
维莫德吉是首个用于治疗基底细胞癌（BCC）的口服药物，最近被批准用于治疗局部晚期或转移性 BCC 患者，这些患者的癌症对标准治疗无反应或不适合手术或放疗。维莫德吉是一种小分子，能强力抑制 hedgehog 信号通路中的信号转导，具有非线性药代动力学特征，半衰期为 13 天。增加胃肠道 pH 值的药物可能会降低维莫德吉的溶解度和生物利用度。该药在局部晚期和转移性 BCC 中均有效，两项临床试验的缓解率在 30%至 60%之间。维莫德吉有 150mg 胶囊剂型，批准的剂量为每日口服 150mg。维莫德吉最常见的不良反应包括轻到中度脱发、肌肉痉挛、味觉障碍和体重减轻。一个月维莫德吉治疗的估计费用为 7500 美元。
维莫德吉最近被批准用于治疗对标准治疗无反应或不适合手术或放疗的局部晚期或转移性 BCC。鉴于其高成本、标准治疗方法的高治愈率以及对非危及生命疾病患者不可接受的毒性特征，维莫德吉对 BCC 的治疗作用可能有限。然而，与细胞毒性化疗相比，维莫德吉的新型作用机制、口服剂型、初步疗效和耐受性可能使其成为治疗其他癌症的有吸引力的候选药物。
