Antitumor activity of recombinant-derived interferon alpha in metastatic renal cell carcinoma.

Abstract

Fifty-six patients with metastatic renal cell carcinoma (RCC) were treated with recombinant DNA-derived interferon alpha (rIFN alpha A). The first 30 patients were randomized between doses of 2 X 10(6) U/m2 and 20 X 10(6) U/m2 intramuscularly daily. No complete (CR) or partial (PR) remissions were achieved in 15 patients receiving the low dose. In contrast, 27% of those receiving the high dose achieved CR or PR. Subsequently, 26 additional patients were given the high dose and achieved a 31% response rate. Remissions lasted from 1 to more than 12 months (median, 3 months). Responses occurred predominantly in lung parenchyma or mediastinal node metastases. Toxicity of the high dose required dose reduction in 50% of the patients. Neutralizing antibodies to rIFN alpha A developed in seven of 12 responsive (58%) and nine of 29 (31%) nonresponsive patients (P = greater than .5). The median duration of remission among the antibody-positive and antibody-negative patients were 2 and 10 months, respectively (P = .009). The clinical significance of the antibodies to rIFN alpha A remains unclear, but the coincidence between the detection of antibodies and the early relapse of the disease in some responsive patients suggests that these antibodies may abrogate the biologic activity of rIFN alpha A. This effect, however, was not associated with adverse clinical sequelae.

Clinical and immune modulatory effects of alternative weekly interleukin-2 and interferon alfa-2a in patients with advanced renal cell carcinoma and melanoma

“…Published clinical trials of INF alpha have reported response rates between 10-17% in renal cell carcinoma and melanoma (Hersey et al, 1985;Quesada et al, 1985). Phase II studies of IL-2 with or without LAK cells have reported tumour responses of 16-31 % in renal cell carcinoma and 14-26% in melanoma (Rosenberg et al, 1988;Fischer et al, 1988;Stahel et al, 1989;Dutcher et al, 1989;Bar et al, 1990), although at the cost of considerable acute toxicity.…”

Subcutaneous low-dose recombinant interleukin 2 and alpha-interferon in patients with metastatic renal cell carcinoma

“…Alpha-interferon (INF-ac) has also shown some therapeutic efficacy in patients with metastatic renal cell carcinoma, resulting in a 15% response rate (Quesada et al, 1985).…”

Effect of Dosing Schedule on Pharmacokinetics of Alpha Interferon and Anti-Alpha Interferon Neutralizing Antibody in Mice

“…Namely, the effective IFN concentration decreases because of the appearance of anti-IFN neutralizing antibodies, resulting in a reduced therapeutic effect. The production of anti-IFN neutralizing antibodies may be influenced by several factors, including dosing schedule (duration, dose, dosing time) and the use of an alternative IFN such as IFN-␣, IFN-␤, or IFN-␥ (17,39,42,46). One simple approach that can be used to prevent or overcome the production of anti-IFN antibodies is the use of a dosing schedule which reduces the level of production of anti-IFN antibodies.…”