Dana-Farber Cancer Institute , Harvard Medical School, Boston, MA 02215, USA.
Expert Opin Drug Saf. 2011 Jul;10(4):645-53. doi: 10.1517/14740338.2011.581660. Epub 2011 Apr 28.
Vinca alkaloid agents have been widely used in several different types of malignancies. However, cancer cells, ultimately, develop resistance to these agents. Therefore, the development of new agents with improved efficacy is warranted. Recently, a new synthetic vinca alkaloid, vinflunine, was developed through the addition of two fluor molecules by superacidic chemistry.
The authors describe the development of the new vinca alkaloid vinflunine from preclinical studies to the late-stage clinical trials, highlighting the most important clinical and safety data of vinflunine. In vitro and in vivo studies have shown a superior efficacy of vinflunine over other vinca alkaloids and with an improved safety profile. Early clinical trials have demonstrated a significant activity of vinflunine against different malignancies. Phase III trials showed that vinflunine increases survival in patients with advanced transitional cell carcinoma of the urothelium (TCCU) tract treated in the second-line and is as effective as docetaxel in second-line NSCLC.
Vinflunine is currently approved in Europe for the treatment of second-line TCCU and is currently being developed in other malignancies. It has been shown to have predictable and manageable adverse effects, such as neutropenia, anemia, constipation and fatigue.
长春碱类药物已广泛应用于多种恶性肿瘤。然而,癌细胞最终会对这些药物产生耐药性。因此,有必要开发新的、疗效更好的药物。最近,一种新型长春碱类药物长春氟宁通过超强酸化学方法添加两个氟分子而合成。
作者描述了新型长春碱类药物长春氟宁从临床前研究到后期临床试验的发展过程,重点介绍了长春氟宁最重要的临床和安全性数据。体外和体内研究表明,长春氟宁比其他长春碱类药物具有更好的疗效,且安全性更好。早期临床试验表明,长春氟宁对不同的恶性肿瘤具有显著的活性。三期临床试验表明,长春氟宁在二线治疗晚期尿路上皮移行细胞癌(TCCU)患者中的疗效优于多西他赛,与二线治疗非小细胞肺癌(NSCLC)的多西他赛疗效相当。
长春氟宁目前已在欧洲获批用于二线治疗 TCCU,目前正在其他恶性肿瘤中进行开发。它的不良反应可预测且易于处理,如中性粒细胞减少、贫血、便秘和疲劳。