It is well known that survival of patients with advanced squamous-cell carcinoma of the head and neck (SCCHN) has not significantly improved despite recent advances in radiation and chemotherapy treatment. Specifically, a very low objective response rate can be obtained in patients with recurrent SCCHN who failed previous chemotherapeutic regimens; the median response duration is invariably short. Clearly, a need exists to explore alternative forms of therapy in this group of patients; the issues of quality of life and treatment-related toxicity must be carefully evaluated as well. Among new investigation areas, the combination of retinoids with cytokines, such as interferons, has been widely tested in both laboratory and clinical settings. A large body of in vitro data strongly supports the potentiation and amplification of the anti-proliferative effect of alpha-interferon 2a (a-IFN 2a) and 13-cis-retinoic acid (13cRA) when used in combination; the association of the 2 agents has been shown to produce a synergistic and more than additive activity on several SCC cell lines Toma et al., 1994). However, important results have been achieved in the clinical setting with such a combination, particularly in cases of squamous carcinoma; pertinent clinical experiences have been published on patients with SCC of the skin and cervix (Lippman et al., 1992a, b) and by our group on advanced SCC of different sites (Toma et al., 1994a, c).
In line with these findings, we have conducted a phase II study to evaluate the feasibility and anti-tumor activity of 13cRA plus a-IFN 2a in patients with recurrent, pre-treated SCCHN.