Novel Formulation of Bortezomib for Multiple Myeloma May Improve Efficacy and Reduce Adverse Events

Researchers at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital have tested a nanomedicine technology in mice formulated to precisely target myeloma cancer cells with a novel bortezomib delivery system.

Researchers at the Dana-Farber Cancer Institute and Brigham and Women’s Hospital (BWH) have successfully tested a nanomedicine technology to precisely target myeloma cancer cells in the bone. These nanoparticles may help drugs penetrate the microenvironment surrounding the bone, allowing more effective penetration of medications into solid tumors and bone.^1,2

In the trial, published on a June 30, 2014 in the Proceedings of the National Academy of Sciences, researchers treated mice with multiple myeloma using bone-homing polymeric nanoparticles composed of 2 polymers: poly(lactic-co-glycolic acid) and polyethylene glycol. Investigators tested the system with 2 medications: alendronate and bortezomib.¹

Researchers used fluorescent probes to assess where the drug was accumulating in mice. The use of targeting polymers improved retention of drugs in certain organs, including the spleen, femur, skull, and lymph nodes.¹

Initial results in mice indicate that bortezomib formulated with the new delivery system improves survival and reduces the tumor burden to a greater degree than a formulation of bortezomib lacking the delivery system. Survival time was increased to 41 days in mice receiving targeted bortezomib versus 34 to 36 days in mice receiving bortezomib without the delivery system.¹

Although researchers were unable to test whether the use of targeting polymers reduced neuropathy symptoms, investigators speculated that targeting polymers may reduce the risk of neuropathy due to its effect on areas other than bone.¹

In a press release, study senior coauthor, Irene Ghobrial, MD of Dana-Farber’s Center for Hematologic Oncology, stated, “This study provides the proof-of-concept that targeting the bone marrow niche can prevent or delay bone metastasis. This work will pave the way for the development of innovative clinical trials in patients with myeloma to prevent progression from early precursor stages or in patients with breast, prostate or lung cancer who are at high-risk to develop bone metastasis.”²

References:

• Swami A, Reagan MR, Basto P, et al. Engineered nanomedicine for myeloma and bone microenvironment targeting [Published online June 30, 2014]. Proc Natl Acad Sci U S A.
• Dana-Farber Cancer Institute. Scientists Engineer Nanoparticles to Prevent Bone Cancer, Strengthen Bones [press release]. http://www.dana-farber.org/Newsroom/News-Releases/Scientists-Engineer-Nanoparticles-to-Prevent-Bone-Cancer-Strengthen-Bones.aspx . Accessed July 2014.