This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. RENAL CELL CARCINOMA AND ITS TREATMENT Renal cell carcinoma (RCC) constitutes ~2% of all malignancies, with an estimated incidence of 30,000 cases per yr and ~12,000 deaths per year in the United States. A steady increase in the incidence of RCC between 1974 and 1990 has been noted. It is believed that improved diagnostic capabilities account for most of this increase. For the 60%-70% of patients with RCC presenting with localized disease, radical nephrectomy represents a potentially curative option, with ~70% of patients who undergo nephrectomy achieving long-term disease control. Unfortunately, for patients who either present with advanced disease (~30% of initial presentations) or develop advanced disease following nephrectomy (~30% of those who undergo potentially curative nephrectomy), treatment remains inadequate. Metastatic RCC is notoriously resistant to radiotherapy, chemotherapy, and hormonal agents. Treatment with biologic response modifiers or with cytokines has resulted in only modest success. Of cytokine therapies, interleukin-2 (IL-2) and interferon (IFN) have shown some evidence of antitumor activity in late-stage clinical trials and are routinely used to treat patients with metastatic RCC. No therapies with demonstrated clinical benefit are available to patients with metastatic RCC whose disease is refractory to, or has relapsed following, cytokine therapy. Moreover, in a recent subset analysis of a Phase III study comparing IL-2, IFN, and the combination of cytokines, only 4 of the 113 subjects (3.5%) who received crossover therapy after failure of initial cytokine therapy achieved an objective response to the other cytokine; toxicity was considerable and consistent with first line treatment.
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