13-CIS-RETINOIC ACID WITH INTERFERON-ALPHA-2A ENHANCES RADIATION CYTOTOXICITY IN HEAD AND NECK SQUAMOUS-CELL CARCINOMA IN-VITRO

The treatment of locally advanced squamous cell carcinomas of the head and neck presents a challenge for oncologists, Radiation therapy alon e fails to control many of these tumors, Chemotherapy added to radiati on therapy has not clearly demonstrated an improvement in survival in the majority of trials reported to date. In this study, we have evalua ted whether IFN-alpha-2a and/or 13-cis-retinoic acid (RA) enhance radi ation cytotoxicity in a head and neck squamous cell carcinoma cell lin e (FaDu), Using a clonogenic cell survival assay, IFN-alpha-2a (1000 u nits/ml) or RA (1 mu M) alone did not significantly enhance radiation cytotoxicity. The combination of the two agents, however, significantl y increased the cytotoxicity of radiation against FaDu cells. The calc ulated survival fraction at 2 Gy was decreased from 0.649 with radiati on alone to 0.477 when combined with the other two agents (P = 0.016), and the MID was decreased from 3.318 to 2.499 Gy (P = 0.028), A Phase I clinical trial to combine IFN-alpha-2a and/or RA in patients with u nresectable head and neck cancer has been initiated.