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CHICAGO – Severe oral mucositis among patients undergoing radiation and platinum-based chemotherapy for locally-advanced head and neck cancers can be significantly reduced by the novel agent avasopasem manganese, researchers reported here.

About 64% of patients assigned to placebo experienced grade 3 or 4 oral mucositis in the ROMAN trial compared with 54% of patients who were treated with avasopasem manganese, a significant 16% relative risk reduction (P=0.045), said Carryn Anderson, MD, a radiation oncologist at the University of Iowa in Iowa City.

In her oral presentation at the annual meeting of the American Society of Clinical Oncology, Anderson also reported other benefits with avasopasem manganese:

• A relative 56% fewer days of severe oral mucositis: 8 versus 18 days (P=0.002)
• A trend for lower incidence of grade 4 oral mucositis: 24% versus 33% (P=0.052)
• Numerically fewer days of grade 4, severe oral mucositis: 5.5 versus 7.2 days (P=0.143)
• A relative 29% longer time to severe oral mucositis onset: median 38 versus 49 days (P=0.002)

"Intensity-modulated radiotherapy plus cisplatin is an established treatment for locally-advanced head and neck cancer, but about 70% of patients develop severe oral mucositis, limiting their ability to eat solids or liquids, and often requiring nutrition by feeding tube," Anderson said. "There are no approved drugs for the treatment of severe oral mucositis."

Avasopasem manganese is a selective small molecule mimetic that converts radiation therapy-induced superoxide to hydrogen peroxide, Anderson explained. Superoxide initiates tissue damage and an inflammatory cascade that results in oral mucositis. She said that avasopasem manganese protects normal cells but doesn't protect cancer cells from radiation therapy.

In the ROMAN trial, patients with oral cavity or oropharynx tumor and locally advanced squamous cell carcinoma were randomized 3:2 to avasopasem manganese 90 mg for 7 weeks – a 60-minute infusion 5 times a week ending about 1 hour before radiotherapy -- or were treated with placebo.

All told, 241 patients were assigned to avasopasem manganese and 166 patients were assigned to the placebo arm. The median age of the patients was 61, about 86% were men and about 82% were diagnosed with oropharyngeal cancer.

In commenting on the study, James Bonner, MD, chairman of radiation oncology at University of Alabama at Birmingham, said, "We need further follow-up, especially regarding cancer outcomes, in order to determine if this agent can be included in our treatment algorithm.

"There were questions raised over whether avasopasem manganese as a 'normal tissue protector' might also protect tumor cells. A normal tissue protector is not helpful if it protects the cancer from treatment as well – a long-standing issue in our field," he said.

"We need this information before advancing these data," Bonner told 番茄社区app. "I suspect that they have undisclosed information, as they mentioned that they are already submitting their results to the FDA for approval. So, it is unlikely that there is any evidence that this therapy diminishes the results of the standard therapeutic response against tumors."

Bonner noted that the therapy is not a simple procedure:

"This treatment requires an intravenous infusion of an hour before every radiation treatment, and it causes nausea. If the benefit is not truly significant, patients and physicians will be hesitant to expose patients to this onerous treatment."

He added that doctors often are focused on cancer-related outcomes, but "severe oral mucositis is a problem that detracts from quality of life, and for patients it is very important."

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