Western Section Program

OBJECTIVES: To determine whether oral administration of FA inhibits HNSCC tumor growth in an animal model. STUDY DESIGN: In vivo murine model, two arm controlled study. METHODS: Thirty-eight 5 week old athymic nude mice were randomly assigned to a fusaric acid treatment group (1 mg/mL) (n=19) or a sterile saline group (n=19). A left, lateral flank subcutaneous injection of 2.0x 106 SCC-1 cells were administered to all mice on day 1. Both groups were gavaged daily with either 0.25 mLs of oral FA or sterile saline throughout the experiment (32 days). Latency to a measurable tumor (365mm3), and tumor volumes were recorded after tumor xenografting using the formula (l ́w2)(p/6). Tumor weights were recorded at the conclusion of the experiment. Tumor volume growth curves were modeled as polynomial functions of time with treatment interaction effects. Survivorship functions for time to measurable tumor were estimated using the Kaplan-Meier product limit estimator. RESULTS: Survival analysis showed mice treated with FA developed measurable tumors after a significantly longer interval post-xenografting than control mice (p=0.00451). By day 9, all mice in the control group had developed measurable tumors in comparison to only 78% of mice in the FA group. Likewise, estimated growth curves for both groups suggested that mice receiving FA demonstrated significantly slower tumor growth rates throughout the entire study period (p<0.0001). At the conclusion of the experiment, tumor weights from both the control and FA groups were also significantly different (p=0.0142). CONCLUSIONS: Orally administered fusaric acid (1mg/mL) is an inhibitor of SCC-1 in a murine model. It may have a potential role in the treatment of human squamous cell carcinoma of the head and neck.