Gentile Massimo, Martino Massimo, Recchia Anna Grazia, Vigna Ernesto, Morabito Lucio, Morabito Fortunato
a Hematology Unit , Azienda Ospedaliera di Cosenza , Cosenza , Italy.
b Hematology and Stem Cell Transplant Unit , Azienda Ospedaliera BMM di Reggio Calabria , Reggio Calabria , Italy.
Expert Opin Investig Drugs. 2016 Jun;25(6):743-9. doi: 10.1517/13543784.2016.1169272. Epub 2016 Apr 6.
Sorafenib is an orally available compound that acts predominantly by targeting the Ras/Raf/MEK/ERK pathway and by inhibiting the vascular endothelial growth factor (VEGF). Since the Ras/Raf/MEK/ERK pathway is implicated in the proliferation of multiple myeloma (MM) cells and VEGF in bone marrow neovascularization, sorafenib is a drug offering the potential for targeting two important pathogenetic mechanisms involved in MM. Thus, sorafenib is being proposed for use in MM.
In this review, the authors discuss the rationale for the use of sorafenib in MM. They then summarize the clinical development of sorafenib in MM, from initial Phase I to Phase II studies. A systematic literature review of the trials was performed using PubMed.
Preliminary data from phase I/II trials showed that sorafenib had a good safety profile but minimal anti-myeloma activity as a single agent in relapsed/refractory patients. Results of phase II trials, evaluating sorafenib combined with new drugs, such as bortezomib and lenalidomide are eagerly awaited.
索拉非尼是一种口服化合物,主要通过作用于Ras/Raf/MEK/ERK通路以及抑制血管内皮生长因子(VEGF)发挥作用。由于Ras/Raf/MEK/ERK通路与多发性骨髓瘤(MM)细胞的增殖有关,且VEGF参与骨髓新生血管形成,索拉非尼是一种有可能针对MM中两个重要致病机制的药物。因此,有人提议将索拉非尼用于MM治疗。
在本综述中,作者讨论了索拉非尼用于MM治疗的理论依据。接着,他们总结了索拉非尼在MM治疗中的临床研发情况,从最初的I期到II期研究。使用PubMed对这些试验进行了系统的文献综述。
I/II期试验的初步数据显示,索拉非尼安全性良好,但作为单一药物用于复发/难治性患者时抗骨髓瘤活性极小。索拉非尼与硼替佐米和来那度胺等新药联合使用的II期试验结果备受期待。