Roswell Park Launches New Clinical Trials for Esophageal Cancer
Esophageal cancer patients often face daunting odds, primarily because the disease is typically advanced at the moment of diagnosis. Progress in developing more effective therapies has lagged, leaving many with limited options. However, researchers at Roswell Park Comprehensive Cancer Center are charting a new path. They have initiated two phase 2 clinical trials investigating whether the addition of a beta blocker called propranolol can significantly improve the efficacy of checkpoint inhibitors— a type of immunotherapy.
Innovative Approach to Enhance Immunotherapy
Approved by the U.S. Food and Drug Administration (FDA) in 1968, propranolol, known by the brand name Inderal, is a beta blocker commonly prescribed for managing high blood pressure. Early clinical and laboratory results suggest this drug may also play a critical role in cancer treatment. Dr. Elizabeth Repasky, PhD, Vice Chair of Immunology and Co-Leader of the Cancer Stress Biology Program at Roswell Park, shared insights into this promising line of research. 'In our earlier laboratory and clinical trials, we demonstrated that beta blockers, like propranolol, strengthen anti-tumor immune cells, giving immunotherapies such as checkpoint inhibitors a much better chance to work,' Dr. Repasky explained.
Dr. Repasky and her team have discovered that propranolol can inhibit adrenergic stress hormones. These hormones tend to be elevated in many cancer patients following their diagnosis and have a suppressing effect on the immune system. By blocking these hormones, propranolol could potentiate the immune response against tumors.
The Clinical Trials
Both trials are currently enrolling patients with adenocarcinomas of the esophagus or gastroesophageal junction. Adenocarcinomas are a form of cancer that arise in glandular tissues of various organs, including the esophagus and stomach. These cancers are particularly aggressive, and for patients with advanced adenocarcinoma, median survival rates hover just above 12 months.
Dr. Sarbajit Mukherjee, MD, MS, a gastrointestinal medical oncologist in Roswell Park’s Department of Medicine and Co-Leader of the GI Translational Research Group, is the principal investigator (PI) for one of these trials. Dr. Mukherjee elaborated on the challenges, 'By the time esophageal cancer is discovered, it usually has spread to nearby lymph nodes or distant organs, making it resistant to traditional treatments.' This sobering reality underscores the urgent need for new treatment protocols.
Combination Therapy for Better Outcomes
The first study, titled 'A phase 2 trial of chemotherapy, pembrolizumab, and propranolol in advanced esophageal/gastroesophageal junction adenocarcinoma patients' (NCT05651594), will enroll 40 patients. They will receive a combination of standard-of-care chemotherapy along with pembrolizumab—a checkpoint inhibitor—and propranolol.
The second study is a randomized clinical trial titled 'Propranolol with Standard Chemoradiation for Esophageal Adenocarcinoma' (NCT04682158). Led by Dr. Singh, this trial will include 60 patients who will receive standard-of-care chemoradiation before undergoing surgery. Some patients will also be randomly selected to receive propranolol. Those already on a beta blocker prior to the study will receive only chemoradiation.
Breaking New Ground
Dr. Singh emphasized the significance of these trials, stating, 'We haven’t made any significant advances against esophageal cancer in many years. These clinical trials offer a significant opportunity to maybe alter the standard of care for this devastating illness.'
The Science Behind the Trials
The Repasky Lab at Roswell Park is pioneering research into the complex relationships between stress and cancer. Their work in thermal medicine and immunosuppression has shown that chronic stress can lead to long-term immunosuppression, appearing to maximize energetically taxing thermoregulatory responses. Reducing the diversion of energy to stress pathways allows the body to mount effective anti-tumor immune responses. These preclinical model findings are now being tested in these clinical trials.
Funding and Future Steps
These clinical trials are funded by Roswell Park and the U.S. Department of Defense. While the focus is currently on esophageal cancer, successful results may pave the way for similar approaches in treating other types of cancer. The ongoing work at Roswell Park is a testament to the unyielding pursuit of better treatment options for cancer patients, offering hope where it's needed most.
For more detailed information about these studies or other clinical trials at Roswell Park, you can call 1-800-ROSWELL (1-800-767-9355) or email [email protected]. Founded in 1898 by Dr. Roswell Park, this comprehensive cancer center remains the only National Cancer Institute-designated comprehensive cancer center in Upstate New York.
Claire Battista
August 21, 2024 AT 01:19Love that they’re testing it in combo with chemo and checkpoint inhibitors. No magic bullets, but this feels like stacking the deck in our favor.
Erin DeGroot
August 21, 2024 AT 14:48It’s not just about killing cancer cells; it’s about giving the immune system a fighting chance. The fact that propranolol targets stress hormones? That’s elegance in medicine. I hope this becomes standard everywhere.
Thank you, Roswell Park, for refusing to accept the status quo.
Stephanie Bryant
August 22, 2024 AT 12:57Drashti patel
August 23, 2024 AT 10:09Imagine if we treated cancer like a system failure instead of a localized explosion. Maybe that’s the real breakthrough here-not the drug, but the paradigm shift.
And yet… I wonder if this will reach the people who need it most. Access, cost, awareness. Science is beautiful, but justice is harder.
Kaitlin Crockett
August 24, 2024 AT 05:08