Sorafenib for the treatment of multiple myeloma

Expert Opin Investig Drugs. 2016 Jun;25(6):743-9. doi: 10.1517/13543784.2016.1169272. Epub 2016 Apr 6.

Abstract

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.

Keywords: Myeloma; Raf inhibitor; sorafenib; target therapy.

Publication types

  • Review
  • Systematic Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bortezomib / administration & dosage
  • Cell Proliferation / drug effects
  • Humans
  • Lenalidomide
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology
  • Niacinamide / adverse effects
  • Niacinamide / analogs & derivatives*
  • Niacinamide / pharmacology
  • Niacinamide / therapeutic use
  • Phenylurea Compounds / adverse effects
  • Phenylurea Compounds / pharmacology
  • Phenylurea Compounds / therapeutic use*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Sorafenib
  • Thalidomide / administration & dosage
  • Thalidomide / analogs & derivatives

Substances

  • Antineoplastic Agents
  • Phenylurea Compounds
  • Protein Kinase Inhibitors
  • Niacinamide
  • Thalidomide
  • Bortezomib
  • Sorafenib
  • Lenalidomide