Low-dose γ-interferon therapy is ineffective in renal cell carcinoma patients with large tumour burden

The efficacy and immunomodulatory effects of low-dose γ-interferon (γIFN) were investigated in an unselected population of patients with metastasising renal cell carcinoma. 36 patients suffering from metastasising renal cell carcinoma with a performance status exceeding Karnofsky index of 50 were entered into the open phase I II trial. The majority of the patients recruited displayed a large tumour burden, and 28 patients (78%) had metastases involving two to six organ sites. Treatment was started with a 2-week cycle of either daily or weekly subcutaneous administration of either 100, 200 or 400 μg γIFN. After a therapy-free interval of 2 weeks treatment was switched to the alternate mode of administration. Subsequently, treatment was continued with the same dose applied once a week for a minimum of 3 months. Serum levels of neopterin and β-2-microglobulin, as well as flow cytometric analyses of peripheral blood mononuclear cells, were used for the assessment of biological response. Minimal antitumour activity was observed in this high-risk patient group and only 1 patient experienced a partial response (PR) lasting 36+ months. Comparison of the patients' characteristics to those of other low-dose γIFN trials revealed a highly significant difference in the tumour burden and clinical response. We conclude that patient selection is a decisive parameter for the outcome of treatment with low-dose γIFN, and that patients with poor prognostic features and a large tumour burden are not likely to respond to this almost atoxic treatment.