The promise of biochemical modulation in combined modality therapy

This paper reviews evidence that interferon (IFN) potentiates the cytotoxicity of radiotherapy or chemotherapy. The results of preclinical models suggest that the radiation-enhancing effect may be due in part to cell-cycle synchronization. Clinical studies of small numbers of patients indicate that IFN may enhance the effect of radiotherapy in localized tumors, such as non-small cell lung cancer and head and neck cancer. Interferon augmented the cytotoxicity of cisplatin in a murine model, but two clinical studies of patients with non-small cell lung cancer had mixed results. Interferon clearly enhances the activity of 5-fluorouracil (5-FU) in a variety of laboratory models. Three studies are under way to evaluate the combined effects of IFN, cisplatin, and 5-FU in patients with head and neck cancer. Investigators at the University of Chicago are obtaining promising results with IFN and chemotherapy in patients with previously untreated stage IV head and neck cancer. The regimen consists of three cycles of induction cisplatin, 5-FU, high-dose leucovorin, and IFN followed by surgery and/or seven cycles of concomitant chemoradiotherapy. Although toxicity was formidable, 51% of 65 evaluable patients achieved complete responses to the chemotherapy. Another combination that holds promise is IFN and 13-cis-retinoic acid. This combination has shown activity in selected solid tumors. The results of available studies indicate that biochemical modulation is feasible and promising. Randomized clinical trials are needed to confirm the role of IFN as a biochemical modulator.