SAN FRANCISCO—Oh, honey... You just don't have what it takes—at least when it comes to reducing radiation-induced esophagitis, researchers reported here at the American Society for Radiation Oncology Annual Meeting.
Compared with best supportive care, neither Manuka honey liquid nor Manuka honey lozenges provided relief for treatment-related esophagitis other than what doctors now often use to control that pain at individual centers, said Lawrence Berk, MD, PhD, Chief of Radiation Oncology at the University of South Florida.
“The problem with doing studies with natural products is that they are natural products and there is no uniformity of the product. Each batch of these products may be different, and there are an infinite number of products, which is particularly true with honey.”
The researchers were hoping to give doctors guidance on how to treat esophagitis—an area where no standard of care exists: “We chose Manuka honey—honey derived from the Manuka tree in New Zealand—because it has been studied; it is a medical honey,” he explained. “It has been used for wound healing. It is regulated by an association that both tests it and oversees its production. They test for its antibacterial activity, not its inflammatory ability. It is commercially available.”
Berk noted that small studies have been published about the use of various honey products in head and neck cancer patients, showing mixed results from Egypt, Iran, Malaysia, and Nepal. Further scrutiny of these trials might find a product that could prove itself in another trial, he said.
For the study he reported, the researchers enrolled patients who were receiving once-daily concurrent chemotherapy—presumed to be platinum based—plus radiation therapy with a total dose of 60 Gy for treatment of lung cancer. The patients were assigned to receive standard supportive care; 100 cc of liquid Manuka honey four times a day during the concurrent chemotherapy and radiation treatments; or 10 cc equivalent Manuka honey in lozenge form four times a day during radiation and chemotherapy treatments.
The honey was donated to the trial by one of the Manuka honey distributors in New Zealand, Berk noted.
Patients kept a pain diary that helped determine swallowing pain as assessed on an 11-point scale at four weeks of radiation therapy—the primary endpoint of the study. That endpoint, though, he noted, was entirely arbitrary, and the researchers also tested a wide variety of secondary endpoints.
Standard of Care Is Individualized
Asked for his perspective for this article, Kenneth Roberts, MD, Professor of Therapeutic Radiology at Yale School of Medicine, said, “Standard of care for managing esophagitis is all individualized. We use a combination of local anesthetic agents, viscous lidocaine-containing mixtures, narcotic pain medicines, agents that reduce acid reflux, and agents that also coat the mucosa.
“But one of the major things we can do to reduce the risk of esophagitis is how we plan out the radiotherapy and being attentive to how much radiation goes to that organ, and then getting to patients to use these therapies to make patients more comfortable. If this particular type of honey had panned out, we would have had a very simple, non-toxic thing to use,” he said.
Berk explained that although the trial had been foreseen as relatively straightforward, the project became subject to almost all the ills that can befall mankind, including an earthquake that shut down production of the product. The trial opened to accrual on February 28, 2012, and accrual was reached by October 15, 2013, despite being suspended twice.
A total of 53 patients were assigned to standard of care, 53 to receive liquid honey, and 54 to lozenge honey. Eventually, the researchers were able to evaluate the effects in 40 patients receiving best supportive care; 41 receiving liquid honey and 38 receiving lozenge honey.
The outcome: There were no differences between standard of care and liquid honey in numerical pain score, nor between the effects of lozenge honey and standard of care at four weeks.
In reviewing the multiple prespecified secondary endpoints, the researchers were able to observe one positive finding: Patients who were taking the lozenge reported a benefit in their numerical pain scores at 12 weeks.
“In the Radiation Trial Oncology Group, we are looking for ways to ameliorate the side effects of the treatments so we could reduce the dose of radiation,” Berk said. “One area that is underexplored is radiation esophagitis. The other area of interest was natural products — the things that patients are interested in but generally aren't commonly investigated within the cooperative group trials.”
He said that the trial might have had a different outcome if a different product had been selected to test. “We were dealing with natural products and I picked one, and it might have been the wrong product. Perhaps the product I selected did not have the appropriate active compound.”
Roberts added that natural products are very difficult to study: “They are not standardized, and there are a lot of claims out there for all sort of different products. This was an attempt to pick one to see if it helped. It's a very benign agent to use, but it didn't show any benefit over standard of care.”