Single-Dose Prevention or Short-Term Treatment with Fibroblast Growth Factor-20 (CG53135-05) Reduces the Severity and Duration of Oral Mucositis

Oral mucositis (OM) is a treatment-limiting condition associated with myelosupressive chemotherapy and radiation therapy. The objective of this study was to evaluate the activity of recombinant human fibroblast growth factor-20 (FGF-20 or CG53135-05) in the prevention and treatment of OM in experimental animals. Oral mucositis was induced in hamsters with 5-fluorouracil (5-FU; 60 mg/kg) on days −4 and −2, followed by targeted irradiation with 30 Gy on day 0. Oral mucositis was scored every other day using severity scores of 0-5. To test for prevention of OM, animals received varying doses of FGF-20 on day 1 or days 1 and 2 after irradiation before the development of symptoms. To test the effects of FGF-20 on established mucositis, animals were allowed to develop early OM (score of 2) before treatment initiation. Animals then received FGF-20 by intraperitoneal (i.p.) administration (12 mg/kg) for 1, 2, 3, or 4 consecutive days. When prevention of OM was tested, administration of FGF-20 (12 mg/kg i.p.) on day 1 or days 1 and 2 resulted in significant reduction in duration of severe OM to 26% (P < 0.003) or 29.4% (P <0.018) of cumulative days, respectively, compared with untreated control animals, which spent 40.2% of cumulative days with OM scores ≥ 3. When the effects of FGF-20 on established mucositis were tested, treatment of animals with FGF-20 for 2, 3, or 4 consecutive days resulted in significant reduction of severe OM to 27.4%, 29.2%, or 18.5% of days, respectively, compared with vehicle-treated control animals, which spent 41.1% of cumulative days with OM scores ≥3 (P < 0.05). These findings support the utility of FGF-20 as a single-dose agent in the prevention of OM. In addition, the positive effects of FGF-20 on established mucositis may permit treatment of patients with OM who may not benefit from prophylactic agents.