Although treatment of brain tumors with radiotherapy is initially effective, the cancer cells are able to repair themselves and the cancer often recurs. A new study from a team at the Sidney Kimmel Cancer Center (Thomas Jefferson University, PA, USA) has provided preliminary evidence that combining radiotherapy with the epigenetic drug panobinostat prevents the cancer cells from repairing themselves. The results of the 12-patient study were reported recently in the Journal of Neuro-Oncology.
The study’s lead author Yaacov Lawrence (Sidney Kimmel Medical College) commented: “We saw synergy between radiotherapy and the agent, panobinostat. Our findings suggest panobinostat makes radiotherapy much more effective”.
All 12 of the patients in the study had high-grade gliomas that had recurred after radiotherapy. Out of the 12 patients tested, eight had been diagnosed with recurrent glioblastoma and four with recurrent anaplastic astrocytoma. Glioblastoma and anaplastic astrocytoma comprise nearly 70% of newly diagnosed gliomas – most individuals with these diagnoses respond initially to radiation before relapsing within 2 years, at which point overall survival is limited to 1 year or less.
“There is no standard treatment for recurrent high grade gliomas. At Jefferson, 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,” commented co-author Adam Dicker (Sidney Kimmel Medical College).
The drug tested in combination with radiotherapy was panobinostat, a histone deacetylase inhibitor already approved for the treatment of multiple myeloma. Panobinostat modifies the expression of around 8% of RNA molecules, in turn modifying protein production and unsetting cancer growth; in addition, panobinostat also functions by switching off the DNA repair enzyme RAD51.
The study reported that patients tolerated the highest dose of panobinostat well and, more excitingly, improved overall survival and progression-free survival were observed. The team state that their study shows enough promise for treatment of aggressive, recurrent brain cancer that a larger, more comprehensive Phase II study is now warranted.
“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,” Lawrence added.