A clinical trial from Rogel researchers used novel cytotoxic therapies and chemotherapy, to try to improve outcomes for laryngeal cancer patients. Although the trial did not show that the approach was beneficial, the knowledge gained to a long history of evolving and re-evaluating standard of care.
A decade ago, the University of Michigan Head and Neck Oncology Group at the cancer center began using an approach called bio-selection, borne from research showing that chemotherapy was able to predict if chemoradiation would be effective in eradicating head and neck cancers.
With bio-selection, patients are given one dose of chemotherapy as a predictor of response. If the tumor shrinks, they go on to receive chemoradiation. If the tumor does not shrink, patients receive surgery upfront.
In the lab, researchers had identified a potential target: the protein BCL2, which is altered significantly in people with head and neck cancer. Moreover, it is highly expressed in those forms of head and neck cancer for which treatments are largely ineffective and is hypothesized to be the mechanism that causes these poor outcomes. Targeted inhibitors including one called AT-101 were developed in Rogel labs to try to reverse the effects of the protein BCL2.
The use of targeted inhibitors like AT-101 plus chemotherapy helped to kill head and neck cancer cells much more effectively. This finding was confirmed in many preclinical studies, so it was moved forward into the clinical trial to test this approach’s potential to translate into improving patient outcomes.
In a trial, researchers combined chemotherapy with AT-101 to try to improve efficacy.
Given that additional chemotherapy drugs often mean more tumor shrinkage, the team incorporated two cycles of chemotherapy, to the AT-101 compound, and evaluated if it would improve the rate of laryngeal preservation.
Unfortunately, this trial, published in Head & Neck, did not show improvement in laryngeal preservation.
Still, Paul Swiecicki, M.D., clinical associate professor in medical oncology, is clear that this is an important part of the research process and, while unsuccessful in the short term, ultimately continues to create questions for researchers to explore and unearth avenues that lead to other paradigm shifts.
He believes the method of bioselection—versus the traditional approach of just chemoradiation and surgery—is still a promising approach to improve patient survival.
