Radiotherapy-induced severe oral mucositis: pharmacotherapies in recent and current clinical trials

ABSTRACT

Introduction

Oral mucositis (OM) is among the most common, damaging side effects of head and neck radiation therapy and may interfere with patients’ ability to comply with optimal treatment.

Areas covered

The increasing unmet clinical need, recent clinical trial successes, and the commercial potential have catalyzed interest in the development of effective intervention for OM. A range of small molecules are under development – some still in the preclinical stage, but others close to NDA submission. This review will focus on those drugs which have recently been assessed in a clinical trial and those which are still under clinical study as a prevention or treatment for radiation-associated OM.

Expert opinion

In response to the unmet clinical need, both the biotechnology and pharmacological industries have been actively pursuing an agent to prevent/treat radiation-associated OM. This effort has been catalyzed by the identification of multiple drug targets which contribute to OM’s pathogenesis. The lessons learned from the many trials which have previously stumbled have led to standardization of clinical trial design, endpoint efficacy definitions, rater assessment, and data interpretation over the past decade. Consequently, results of recently completed clinical trials provide optimism that effective treatment options should be available in the not-too-distant future.

KEYWORDS:

• Oral mucositis
• trials
• oral mucositis management
• new agents
• radiation therapy

Article highlights

• Oral mucositis is a common intolerable and costly toxicity of radiation therapy for head and neck cancers.

• Radiation-associated mucositis serves as a model for other forms of radiation-induced epithelial injury.

• New agents are currently in the pipeline for the prevention and/or management of radiation induced oral mucositis.

• Most current treatment strategies are primarily supportive care and analgesia.

• The outcomes of recently completed trials support an interventional approach that is mechanistically based, and which targets the biological initiators of oral mucositis.

Declaration of interest

S Sonis is a full-time employee of Biomodels, LLC, and Primary Endpoint Solutions, LLC; he owns equity in both companies and reports participation in scientific advisory boards as a component of his employment; both companies assist industry, government, and academics to study and enable drugs, biologicals, and devices to treat patients for a variety of indications, including oral mucositis, and their employees are prohibited from having equity in any of the companies with which they work.

A Villa receives royalties from UpToDate and is a consultant for Merck, Afyx Therapeutics and Lipella Pharmaceuticals.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.