Successful treatment of metastatic renal cell carcinoma with a biologically active dose of recombinant interferon-gamma.

Abstract

We tested the clinical efficacy of a biologically active dose (BAD) of interferon (IFN)-gamma for treatment of progressive renal cell carcinoma (RCC). Twenty-two RCC patients with disease progression subsequent to nephrectomy were entered on a phase II clinical trial. During an initial dose-finding phase, biochemical responses to repeated once-weekly subcutaneous injections of 10, 100, or 500 micrograms of recombinant IFN-gamma were tested in 16 patients. Results indicated that 100 micrograms IFN-gamma applied once weekly was biologically active with induction of serum beta 2-microglobulin and neopterin. Such a dose induced a nearly maximum response of both markers lasting more than 4 days. This dose was also associated with minimal side effects. A dose of 100 micrograms IFN-gamma given once weekly was, therefore, subsequently given weekly for long-term treatment. During a median time of therapy of 10 months (range, 2 to 32 months) two complete (CR; 20+, 20+ months) and four partial tumor responses (PR; 6+, 7+, 8+, 24+ months) were seen (30% CR plus PR; 95% confidence limits, 12% to 54%) among 20 patients evaluable for response. Patients with refractory disease had significantly lower IFN-gamma-induced increments of serum beta 2-microglobulin than those who achieved clinical remission or stable disease.

Alternating Immune Therapy in Renal Cell Carcinoma

“…Interferon-alpha (IFN-alpha) and interleukin-2 (IL-2) have proved most effective agents with an overall response rate of 14 and 18%, respectively [2]. Similar results were obtained with a low-dose interferon-gamma (IFN-gamma) monotherapy [3], We present a 58-year-old female with metastatic RCC treated with an alternating regime of IFN-gamma and combined IFNalpha/IL-2. Immune therapy with subcutanous IFN-alpha and recombinant IL-2 was started in September 1989.…”

“…Abdominal CT: diameter of liver mass 5.5 x 6 cm, small increase in comparison to January. Therefore, we started a therapy with low-dose recombinant IFN-gamma (Polyferon®, Rentschler, Lauphcim, Germany) [3]. It was injected subcu taneously once a week at a dose of 150 pg.…”

Delayed and acute effects of interferon-γ on activity of an inwardly rectifying K+ channel in cultured human proximal tubule cells

“…Thus the IFN-␥-induced cell injury might be related to its effects on K ϩ channel activity. It is also of note that IFN-␥ is sometimes used for the treatment of renal cell carcinoma (2,18). Considering that it might cause renal cell injury, special attention should be paid to its therapeutic use.…”

Gene transfer of human interferon gamma complementary DNA into a renal cell carcinoma line enhances MHC-restricted cytotoxic T lymphocyte recognition but suppresses non-MHC-restricted effector cell activity

“…However, clinical benefit is not long lasting and is often accompanied by serious toxicity. 6,[46][47][48] One study reported good clinical responses following systemic IFN␥ treatment 49 but similar results have not been seen in other patients. 6,50,51 Because of the toxicities associated with systemic interferon application this form of treatment is not suitable for patients with low performance status or as an adjuvant therapy for patients with minimal residual disease.…”