[Combination of chemotherapy and immunotherapy in man--review]

Abstract

Such biological response modifiers (BRMs) as interferon, interleukin-2 and tumor necrosis factor were shown to have some antitumor activity in man. In addition, preclinical studies have demonstrated favorable interactions of these BRMs and chemotherapeutic agents. Animal studies have shown cure in certain combinations. Therefore, it has become important to study whether combinations of these BRMs and chemotherapeutic agents would increase response rate, survival and/or the quality of life in patients with cancer. In this review entire articles on this subject published in English literature were evaluated to assess current status. While there were isolated articles describing improved response rates, a majority of articles failed to document clinical benefit from the combinations. Some articles recorded increased toxicity without therapeutic benefit. At this time there was only one published phase III study comparing chemotherapy and the chemotherapy combined with BRM, in this case interferon: response rate and survival were identical in the two groups. The review of these articles resulted in identification of several factors considered to be associated with the discrepancy between preclinical data vs. clinical results: larger tumor load in man as compared to animals, importance of pharmacokinetic barrier which can not be incorporated in in vitro systems, differences in dosing schedules between animals and man, and differences in assessing response. Presence of negative preclinical data can not also be ignored. It is concluded that in order for better assessment of this modality of treatment further phase III studies are needed. Therapeutic effects may improve if dose scheduling are optimized and patients with small tumor load are studied preferentially.