Combination Therapy May Be Better Than Radiotherapy Alone to Treat Aggressive Brain Cancer, According to Early Study
Radiotherapy effectively damages brain tumors, but the cancer cells can repair themselves in order to live on. Now, researchers at Sidney Kimmel Cancer Center at Thomas Jefferson University have tested a strategy that combines radiotherapy with a drug that shuts down the ability of tumor to mend themselves.
According to the researchers, their 12-patient phase I study, published by Shi et al in the Journal of Neuro-Oncology, offers enough promise that a more comprehensive phase II clinical trial should be conducted to test the combination therapy for aggressive, recurrent brain cancer.
“We saw synergy between radiotherapy and the agent panobinostat [Farydak]. Our findings suggest panobinostat makes radiotherapy much more effective,” said Yaacov R. Lawrence, MD, of the Department of Radiation Oncology at Thomas Jefferson University's Sidney Kimmel Medical College.
All 12 patients tested had high-grade gliomas that had recurred after initial radiotherapy. Eight patients had recurrent glioblastoma, and four had recurrent anaplastic astrocytoma. These two forms of aggressive brain cancer represent almost 70% of newly diagnosed gliomas, which are diagnosed in about 10,000 patients annually. Despite response to initial radiation, most patients relapse within 2 years, and overall survival is then limited to 1 year or less.
No Standard Treatment
“There is no standard treatment for recurrent high grade gliomas…. We have a lot of experience with offering a second course of radiation after a patient relapses, in order to increase survival, but we are excited by the promise of a targeted agent that makes initial and repeat radiotherapy more effective,” said Adam Dicker, MD, PhD, FASTRO, Chair and Professor of Radiation Oncology, Pharmacology, and Experimental Therapeutics at the Sidney Kimmel Medical College.
Panobinostat, approved for use in 2015 for treatment of multiple myeloma, is being tested in a variety of other cancers. It is a histone deacetylase inhibitor that has been shown to modify expression of about 8% of RNA molecules produced from genes. Modifying RNA changes protein production, disrupting cancer growth. The drug also turns off RAD51, a DNA repair enzyme, Dr. Dicker said.
Researchers found that the highest dose of panobinostat tested in patients was well tolerated, and they observed improved progression-free survival and overall survival.
“The intent of this study was not to demonstrate benefit of the combination therapy but to test safety. Still, we did note promising activity, which must be validated in further studies,” Dr. Lawrence said.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
