Mucosal damage: a major risk factor for severe complications after cytotoxic therapy

Abstract

The oral and gastrointestinal mucosa is frequently damaged during chemotherapy and radiotherapy in patients with cancer, leading to a high incidence of mucositis (ie, oral, esophageal, lower gastrointestinal tract mucositis). Patients with mucositis often experience considerable pain and discomfort. Furthermore, neutropenic patients with mucositis have an increased risk of potentially life-threatening infections as well as prolonged hospital stays. Mucositis may also require that subsequent chemotherapy or radiotherapy doses be reduced, thereby potentially compromising the efficacy of cancer therapy. Standard care for oral mucositis is based on effective oral hygiene, appropriate analgesia, infection management, and parenteral nutrition when needed; few other approaches have been shown to be effective. The evaluation of new options to treat and prevent mucositis rather than control the symptoms is therefore an urgent priority. A comprehensive understanding of the complex pathobiology of mucositis will help to identify potential targets for new drugs. Promising investigational approaches have recently emerged. These include fibroblast growth factor-20, which is effective in animal models of chemotherapy/radiation-induced mucosal toxicity, and is being investigated in clinical studies. The candidate that is most advanced in terms of drug development is recombinant human keratinocyte growth factor (rHuKGF; palifermin), which in phase III clinical trials was shown to reduce the severity and duration of oral mucositis and improve clinical sequelae.