Biologic response modifiers in genitourinary neoplasia

With the exception of testis cancer, the variety of genitourinary cancers have not been found to be consistently responsive to chemotherapeutic agents or regimens for other than anecdotal short duration. This has generated keen interest in the possibility that biologic response modifiers might either directly or through manipulation of immune response mechanisms successfully prevent tumor progression in these systems. In recent years, those substances that have attracted the greatest attention have included interferon (and, more recently, recombinant gamma interferon), bacillus Calmette-Guerin (BCG), tumor necrosis factor, prostaglandin synthetase inhibitors, and interleukin-2. Results with each of these agents in the variety of genitourinary cancers have been both promising and disappointing. A number of mechanisms have been suggested to underlie the actions of each of these substances, and the successful or unsuccessful recruitment of these mechanisms, in the context of the particular intrinsic behavior of the cancers being treated, have been suggested as reasons for the treatment results that have been seen. Therapeutic efficacy has been described in the treatment of renal cell cancer by both systemic interferon and interleukin-2. Successful treatments have been reported in approximately 20% of patients treated with each substance, but generally, these results have been of short duration. Topical BCG has been used with great success to treat superficial transitional cell bladder cancer. In these instances, the generation of tumor necrosis factor has been suggested as possibly accounting for the 70% success rate both in therapy and prophylaxis that has been seen. Leukocyte-derived interferon and, more recently, recombinant gamma interferon, were found in initial trials to generate a 20% response rate in renal cell carcinoma patients. Enthusiasm for these agents, however, has been tempered more recently both by a failure to reproduce these results with any substantial duration as well as by the significant side effects that have been seen. Clearly, these agents continue to be intriguing both because of their intellectual appeal through the mechanisms by which they may be effective, as well as by the absence of any definitive therapy for the cancers they are being used to treat. An understanding of the complex host/tumor cell interaction that may ultimately determine therapeutic efficacy for each of these agents is undoubtedly critical if the role of these substances in the treatment of genitourinary cancer is to be successfully implemented, either alone or in combination with other treatment modalities.