alpha Interferon: the potential drug of adjuvant therapy: past achievements and future challenges

This paper aims to summarize current experience with alpha interferon and provide direction for future study. There are four areas in which alpha interferon has proven or potential activity: antiviral, premalignant, adjuvant and advanced disease settings. The three main viral diseases in which interferon alfa-2b has been shown to have activity are chronic viral hepatitis, acquired immunodeficiency syndrome, and human papilloma virus infections. In vitro studies suggest that alpha interferon may inhibit transformation of some premalignant conditions into malignant disease; e.g., vaginal intraepithelial neoplasia. In the adjuvant setting, it is possible that a biological response modifier, such as alpha interferon, may have a role in helping the immune system to destroy residual tumour cells following tumour bulk reduction with radiation or chemotherapy. A higher response rate has been seen in patients with small tumour bulk compared to those with large tumour bulk (e.g., malignant melanoma, ovarian carcinoma), and in patients with early, rather than late, disease (e.g., chronic myelogenous leukaemia, hairy cell leukaemia, multiple myeloma, non-Hodgkin's lymphoma). This may be due to efficacy in a small tumour bulk setting or due to an immunoadjuvant role. In advanced disease, the question is how best to exploit the possible synergistic effects between alpha interferon and other therapeutic modalities. The optimum dose, schedule and patient populations for combined treatment have yet to be determined. The major objective of this paper is to determine how best to capitalize upon the current state of knowledge to build for future trials of alpha interferon, and to determine whether the existing data suggest an adjuvant role for interferon after initial tumour regression.