Researcher Publishes in Lancet, Leads Clinical Trial Testing Heavy Metal

A physician-scientist at the University of Oklahoma is part of an international effort seeking new options for patients with head and neck cancer who cannot receive the standard chemotherapy drug cisplatin.

Because cisplatin can damage the kidneys and cochlea, patients who have kidney problems or hearing loss are usually not candidates to take the drug. The search for alternatives has been challenging. University of Oklahoma radiation oncologist Christina Henson, M.D., is a co-author of a recent publication in the journal Lancet that tested the effectiveness of the immunotherapy drug durvalumab combined with radiation therapy, as an alternative to cisplatin. Durvalumab was compared to another immunotherapy drug, cetuximab.

“In clinical trials, cetuximab has proved effective and doesn’t damage hearing or the kidneys, but it also has a lot of side effects, including a significant full-body rash,” Henson, an associate professor of radiation oncology in the OU College of Medicine, said. “So we want to find substitute medications that can work as well as cetuximab but with fewer side effects, especially because we are often treating older patients who are more frail.

“Unfortunately, in this study, durvalumab did not perform better than cetuximab when given with radiation therapy,” she added. “In fact, patients fared worse on durvalumab. In the end, it was probably no better than radiation alone. The results were disappointing, but negative clinical trials are also very important. They guide you in the direction to look next.”

Henson and her colleagues have taken the next step toward new answers with a clinical trial that studies the effectiveness of a heavy metal injected into the tumor to make it more sensitive to radiation, an approach quite different than chemotherapy and immunotherapy.

The metal, called hafnium, is inert and harmless to the patient, but once it is inserted into the tumor and receives radiation, it enhances radiation’s ability to kill cancer cells. OU is among 160 sites worldwide enrolling patients in the clinical trial, called NANORAY-312.

“This metal agent is designed to increase the amount of radiation that is absorbed by the tumor, without damaging healthy tissues,” Henson said. “We are excited to explore this avenue for patients with head and neck cancer who cannot receive cisplatin, and hope that it provides new options.”

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About the Project

The Lancet study, “Radiotherapy with cetuximab or durvalumab for locoregionally advanced head and neck cancer in patients with a contraindication to cisplatin (NRG-HN004): an open-label, multicentre, parallel-group, randomised, phase 2/3 trial” can be found at https://doi.org/10.1016/S1470-2045(24)00507-2. More information about the heavy metal clinical trial can be found at https://clinicaltrials.gov/study/NCT04892173.