Immunotherapy of renal cell carcinoma.

The clinical trials of immunotherapy of renal carcinoma have been based on the theory that manipulation of the host-immune response can influence the growth of malignant cells in the host. The results cited above do not demonstrate a clear therapeutic role of immunotherapy but they do provide evidence to encourage further studies. This is especially pertinent in view of the current absence of effective systemic agents. The stimulation of the host response appears to be finite and cannot be expected to control massive tumor burden. The clinical trials analyzed above must be interpreted with this understanding. It remains necessary to test new approaches in patients with measurable disease, but stimulation of the immune response is finite and immunotherapy is probably best utilized as systemic adjuvants or in patients with limited metastases. However, the paramount task of those interested in immunotherapy of renal carcinoma remains adherence to the proper progression from Phase I to Phase II and finally to randomized Phase III trials. The natural history of this tumor confounds interpretation of many studies and can only be placed in proper context through the randomized trial mechanism. In the analysis of results of immunotherapeutic and other trials of advanced renal cancer, more careful attention must be given to the specific nature of the patient's disease. In all of the trials discussed above, responses were noted primarily in patients with limited pulmonary metastases. Indeed, since it is necessary that measurable disease be present for inclusion into most trials, this type of patient is the one most commonly treated. It is this group of patients who are most likely to undergo spontaneous regression or to have prolonged periods of stabilization without any other treatment. In addition, the impact of adjunctive nephrectomy in these patients must be clarified. The pulmonary metastases seem to behave differently than lesions at other sites and certainly seem to respond to almost any form of therapy far better than lesions at other sites. The significance of stratification of patients in randomized Phase III trials is therefore obvious and a true understanding of the therapeutic implications of our interventions can only be substantiated by careful randomized studies.