Alfa interferon: combinations with other antineoplastic modalities

Early laboratory work demonstrated synergism from the combination of various cytotoxic agents and alfa interferon against various cell lines. In conjunction with anecdotal clinical reports of this synergism, multiple clinical trials were initiated to determine the tolerance and toxicity of the alfa interferons in conjunction with other antineoplastic agents/modalities. Phase I-II studies have been completed with alfa interferon and melphalan/prednisone, vincristine, vinblastine, etoposide (VP-16), cyclophosphamide, and radiation. In general, it may be stated that the toxicities are nonoverlapping and not unexpected. The tolerable doses of the interferons (IFNs) have generally been low. The future of research with interferon may be divided into three areas: Efforts must be made to determine how best to translate the in vitro synergy into clinically meaningful terms; in order to exploit the fullest potential of IFN, research is moving toward using this agent earlier in disease either as an adjuvant after tumor debulking or after initial diagnosis; the medical community must rethink the natural history of some diseases, because the fullest potential of the biologic agents will most likely manifest itself when these agents are used together.