A Drug Preventing Radiotherapy-Related Mouth Sores to an Unprecedented Degree

A new agent may substantially reduce severe oral mucositis (mouth and throat sores) in head and neck cancer patients receiving radiation therapy. In a phase 2 clinical trial,the new agent GC4419reduced the duration of severe radiation-induced oral mucositis by % 92 as the reduction.

The findings were presented on 19-23 August 2018 at the American Chemical Society (ACS) annual meeting in Boston, Massachusetts.

Dennis Riley, chief scientific officer at Galera Therapeutics, the company developing this drug candidate, said at a press conference, "Approximately % 50 of all solid cancers (solid tumors) are treated with radiotherapy . Radiotherapy has many benefits as a cancer treatment, but a major adverse effect is inflammation , and radiotherapy's adverse effects on normal tissue limit the delivery of high doses to the tumor."

Radiotherapy causes inflammation because it breaks chemical bonds, and approximately % 85 of the body's chemical bonds consist of "water" bonds between oxygen-hydrogen (OH) molecules. Irradiation generates superoxide molecules that are highly toxic (harmful) in the body. Superoxide is more toxic to normal cells than to cancer cells.

GC4419 converts harmful superoxide into oxygen and hydrogen peroxide as a first-in-class superoxide dismutase mimetic (meaning it acts like a converting enzyme).

Thus superoxide, which harms normal cells, is converted into hydrogen peroxide, which is toxic to cancer cells. GC4419 may therefore not only reduce adverse effects but also have antitumor activity.

Study details

This phase 2 study enrolled patients without metastasis — 223 patients with squamous cell head and neck cancer (mostly in the oral cavity and pharynx).

Patients were divided into 3 arms:

• Group A received daily 30 mg GC4419 (a 60-minute intravenous infusion 60 minutes before radiotherapy)
• Group B received daily 90 mg GC4419 using the same protocol; and
• Group C received daily, using the same protocol, placebo as treatment.

Results

• The placebo group had symptoms (complaints) of severe oral mucositis for around 3 weeks, and most had a gastrostomy tube placed for feeding (a tube surgically inserted through the abdominal skin directly into the stomach).
• The mean duration of severe oral mucositis was 19 days with placebo; with GC4419 at 30 mg it was 8 days, and at 90 mg it was 1.5 days in duration.

The very marked reduction in mouth sore frequency, particularly with the 90 mg dose, was striking.

GC4419 is preparing to enter phase 3 clinical trials this year. If further trials succeed and GC4419 receives FDA approval, it could prevent adverse effects from radiation treatment of other cancers (for example, lung cancer, pancreatic cancer and lymphoma).

This study is also an excellent example of how basic medical knowledge, such as "neutralizing oxygen radicals through cellular processes", can be transformed through scientific research into a drug for clinical use benefiting patients.

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