13-CIS retinoic acid and interferon-α ± irradiation in the treatment of squamous-cell carcinomas

Abstract

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 (Bollag et al., 1992;Hoffmann et al., 1995).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;Alberts et al., 1993;Dmitrovsky and Bosl 1992;Roth et al., 1994).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 (Hoffmann et al., 1994).In addition, it has been shown that vitamin A and its derivates potentiate the response of experimental animal tumors to radiation (Tannock et al., 1972;Seifter et al., 1983).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.