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Sorafenib for the treatment of multiple myeloma
Massimo Gentile1, Massimo Martino2, Anna Grazia Recchia3
1a Hematology Unit , Azienda Ospedaliera di Cosenza , Cosenza , Italy.
Introduction:
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.
Areas Covered:
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.
Expert Opinion:
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.
Insights
Sorafenib shows promise for multiple myeloma (MM) by targeting key pathways. Early trials indicate a good safety profile but limited efficacy as a single agent in relapsed/refractory MM patients.
Area of Science:
- Oncology
- Pharmacology
Background:
- Sorafenib targets the Ras/Raf/MEK/ERK pathway and inhibits vascular endothelial growth factor (VEGF).
- The Ras/Raf/MEK/ERK pathway is crucial for multiple myeloma (MM) cell proliferation.
- VEGF plays a role in bone marrow neovascularization in MM.
Purpose of the Study:
- To review the rationale for using sorafenib in MM treatment.
- To summarize the clinical development of sorafenib in MM.
- To assess sorafenib's potential in MM therapy.
Main Methods:
- Systematic literature review of clinical trials using PubMed.
- Analysis of Phase I and Phase II studies of sorafenib in MM.
- Review of sorafenib's mechanism of action.
Main Results:
- Preliminary Phase I/II trials indicate sorafenib has a favorable safety profile.
- Sorafenib demonstrated minimal anti-myeloma activity as a monotherapy in relapsed/refractory patients.
- Further evaluation is needed for combination therapies.
Conclusions:
- Sorafenib is a potential therapeutic agent for MM due to its dual-targeting mechanism.
- Combination therapies involving sorafenib are under investigation.
- Results from Phase II trials combining sorafenib with bortezomib and lenalidomide are anticipated.
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