Patients with localized renal-cell carcinoma who are candidates for renal parenchymal sparing surgery are being treated with isolated renal perfusion with recombinant human tumor necrosis factor (TNF). Isolated organ perfusion is a surgical technique that allows a cancer-bearing organ or region of the body to be treated with high doses of chemotherapy or biologic, agents that would not be tolerated systemically. In patients with in-transit melanoma or unresectable sarcoma, treatment with hyperthermic isolated limb perfusion using TNF, interferon-y, and melphalan has resulted in response rates exceeding 90%. Because preclinical studies suggest that TNF may induce regression of tumors by causing hemorrhagic necrosis mediated by effects on tumor-related vascular endothelium, a vascular tumor such as renal-cell carcinoma could potentially be very responsive. A phase I study of escalating TNF doses delivered via isolated renal perfusion is currently being conducted.
It is estimated that 27,600 new cases of renal-cell carcinoma (RCC) would be diagnosed in the United States in 1994 and that 11,300 patients would die [11]. The incidence of renal cancer has been steadily increasing over the last 30 years and is now more than 1.5 times greater than that found in the early 1960s [11]. For patients with RCC and a normal contralateral kidney, radical nephrectomy is the standard therapy, which provides good overall survival, particularly for patients with low-stage disease. However, a great deal of functioning renal tissue can be removed by radical nephrectomy, and in some patients this can result in substantial morbidity from renal insufficiency. This is particularly worrisome in patients with small, single RCC lesions in an otherwise normal kidney.