Pre-clinical data indicate that retinoid/interferon combinations have significant activity in modulating malignant cell growth, differentiation and programmed cell death in different hematologic and solid tumor systems . Clinically, the combination of 13-cis retinoic acid (13cRA) and interferon-a (IFN-a) has been studied in a variety of tumor types and was identified to have, among others, substantial activity in advanced squamous-cell carcinomas (SCCs) of the skin and the cervix (Lippmann et al., 1992a,b;. Since radiotherapy (XRT) is a substantial part of the treatment of SCC, the question arises as to whether the therapeutic results obtainable with radiation alone can be further improved by using the additive effect of a systemic treatment with 13cRA and IFN-a. The rationale for this approach is based on experimental data since both IFN and retinoids have been demonstrated to synergistically potentiate the radiation toxicity of human SCC cells . In addition, it has been shown that vitamin A and its derivates potentiate the response of experimental animal tumors to radiation .
We evaluated prospectively the feasibility and toxicity of such a combination, using 13cRA and IFN together with simultaneous radiation in SCCs of different origin, and compared our results with a group of patients treated systemically with 13cRA and IFN-a alone.