Recombinant interferon-alpha combined with prednisone in metastatic renal cell carcinoma reduced toxicity without reduction of the response rate—a phase II study

Abstract

Five responses (lung metastases, three; lymph node metastases, two) were observed in 23 patients with metastatic renal cell carcinoma who received recombinant interferon-alpha-2A (IFN) 18 X 10(6) U in three intramuscular doses each week combined with oral prednisone (10 to 20 mg daily). The response duration was 4+, 4+, 9, 11+, and 15+ months. In general, the combination treatment of interferon and prednisone lead to a significant reduction of the subjective side effects (flu-like symptoms) as compared to a previous experience in patients treated with interferon only. Reduction of the interferon dose or discontinuation of IFN treatment was necessary in only two of 23 patients receiving IFN plus prednisone. Prednisone, however, had little effect on the hepatic toxicity often associated with high-dose IFN treatment. The subjective tolerability of a high dose of IFN is significantly increased if oral prednisone (10-20 mg) is given concomitantly in patients with metastatic renal cell carcinoma without reducing the response rate. Randomized trials will be necessary to confirm the efficacy of the IFN and prednisone combination. In addition, higher doses of IFN combined with prednisone should be evaluated in this malignancy.

An Update on the Treatment of Hemangiomas in Children With Interferon Alfa-2a

“…This study is the second (to our knowledge) to document neurological complications in infants and children receiving relatively low-dose interferon alfa-2a for hemangiomas. As with the central and peripheral neurological signs reported previously, 11,[25][26][27][28][29][30] gait and fine motor abnormalities resolved within weeks of the discontinuation of therapy. Interestingly, neurological abnormalities have not been reported in patients receiving comparable doses for viral hepatitis, [32][33][34] a discrepancy that may be the result of age differences.…”

“…In both studies, the gait abnormalities resolved with cessation of interferon alfa-2a therapy. In contrast, Fosså et al 27 reported no neurotoxic effects in 23 patients with renal cell carcinoma treated with 18 million U/m 2 of interferon alfa-2a 3 times a week and oral prednisone (10-20 mg/d).…”

“…Although uptake of interferons in the central nervous system has not been demonstrated, neurological toxic effects have been reported in up to 34% of adult patients with cancer treated with interferon alfa-2a at dosages of 5 to 18 million U/m 2 per day. [25][26][27][28][29][30] These central nervous system effects are presumably due to induced toxic proteins, such as cytokines (eg, interleukin 1). 24 Kemeny et al 25 reported that of 38 patients receiving a combination of interferon alfa-2a and fluorouracil for advanced colorectal cancer, 34% developed gait abnormalities and 16% displayed memory disturbances.…”

An Update on the Treatment of Hemangiomas in Children With Interferon Alfa-2a

“…This study is the second (to our knowledge) to document neurological complications in infants and children receiving relatively low-dose interferon alfa-2a for hemangiomas. As with the central and peripheral neurological signs reported previously, 11,[25][26][27][28][29][30] gait and fine motor abnormalities resolved within weeks of the discontinuation of therapy. Interestingly, neurological abnormalities have not been reported in patients receiving comparable doses for viral hepatitis, [32][33][34] a discrepancy that may be the result of age differences.…”

“…In both studies, the gait abnormalities resolved with cessation of interferon alfa-2a therapy. In contrast, Fosså et al 27 reported no neurotoxic effects in 23 patients with renal cell carcinoma treated with 18 million U/m 2 of interferon alfa-2a 3 times a week and oral prednisone (10-20 mg/d).…”

“…Although uptake of interferons in the central nervous system has not been demonstrated, neurological toxic effects have been reported in up to 34% of adult patients with cancer treated with interferon alfa-2a at dosages of 5 to 18 million U/m 2 per day. [25][26][27][28][29][30] These central nervous system effects are presumably due to induced toxic proteins, such as cytokines (eg, interleukin 1). 24 Kemeny et al 25 reported that of 38 patients receiving a combination of interferon alfa-2a and fluorouracil for advanced colorectal cancer, 34% developed gait abnormalities and 16% displayed memory disturbances.…”

Feasibility of prolonged use of interferon‐α in metastatic kidney carcinoma

“…1,5,7,17 Interferon-␣ has been as effective as a single agent or in combinations with interleukin-2, 8,14 vinblastine, 18 -20 and 5-fluorouracil. 21,22 The response rates have varied from 10% to 40%, most often from 15% to 20%.…”

“…4 -6 The average response rate to the most effective treatments of metastatic RCC rarely exceeds 20%. 5,7 Immunotherapy with interleukin-2 and/or interferon (IFN)-␣ currently is regarded as the most effective therapy for metastatic RCC, 5,8 -11 whereas only a few patients have responded to IFN-␤ or INF-␥. [12][13][14] Therefore, an appropriate approach to the treatment of patients with RCC outside of clinical studies is to use interferon-␣ or interleukin-2 alone or a combination of low-dose interleukin-2 and interferon-␣.…”

An Update on the Treatment of Hemangiomas in Children With Interferon Alfa-2a

“…This study is the second (to our knowledge) to document neurological complications in infants and children receiving relatively low-dose interferon alfa-2a for hemangiomas. As with the central and peripheral neurological signs reported previously, 11,[25][26][27][28][29][30] gait and fine motor abnormalities resolved within weeks of the discontinuation of therapy. Interestingly, neurological abnormalities have not been reported in patients receiving comparable doses for viral hepatitis, [32][33][34] a discrepancy that may be the result of age differences.…”

“…In both studies, the gait abnormalities resolved with cessation of interferon alfa-2a therapy. In contrast, Fosså et al 27 reported no neurotoxic effects in 23 patients with renal cell carcinoma treated with 18 million U/m 2 of interferon alfa-2a 3 times a week and oral prednisone (10-20 mg/d).…”

“…Although uptake of interferons in the central nervous system has not been demonstrated, neurological toxic effects have been reported in up to 34% of adult patients with cancer treated with interferon alfa-2a at dosages of 5 to 18 million U/m 2 per day. [25][26][27][28][29][30] These central nervous system effects are presumably due to induced toxic proteins, such as cytokines (eg, interleukin 1). 24 Kemeny et al 25 reported that of 38 patients receiving a combination of interferon alfa-2a and fluorouracil for advanced colorectal cancer, 34% developed gait abnormalities and 16% displayed memory disturbances.…”

Feasibility of prolonged use of interferon‐α in metastatic kidney carcinoma

“…1,5,7,17 Interferon-␣ has been as effective as a single agent or in combinations with interleukin-2, 8,14 vinblastine, 18 -20 and 5-fluorouracil. 21,22 The response rates have varied from 10% to 40%, most often from 15% to 20%.…”

“…4 -6 The average response rate to the most effective treatments of metastatic RCC rarely exceeds 20%. 5,7 Immunotherapy with interleukin-2 and/or interferon (IFN)-␣ currently is regarded as the most effective therapy for metastatic RCC, 5,8 -11 whereas only a few patients have responded to IFN-␤ or INF-␥. [12][13][14] Therefore, an appropriate approach to the treatment of patients with RCC outside of clinical studies is to use interferon-␣ or interleukin-2 alone or a combination of low-dose interleukin-2 and interferon-␣.…”

An Update on the Treatment of Hemangiomas in Children With Interferon Alfa-2a

“…This study is the second (to our knowledge) to document neurological complications in infants and children receiving relatively low-dose interferon alfa-2a for hemangiomas. As with the central and peripheral neurological signs reported previously, 11,[25][26][27][28][29][30] gait and fine motor abnormalities resolved within weeks of the discontinuation of therapy. Interestingly, neurological abnormalities have not been reported in patients receiving comparable doses for viral hepatitis, [32][33][34] a discrepancy that may be the result of age differences.…”

“…In both studies, the gait abnormalities resolved with cessation of interferon alfa-2a therapy. In contrast, Fosså et al 27 reported no neurotoxic effects in 23 patients with renal cell carcinoma treated with 18 million U/m 2 of interferon alfa-2a 3 times a week and oral prednisone (10-20 mg/d).…”

“…Although uptake of interferons in the central nervous system has not been demonstrated, neurological toxic effects have been reported in up to 34% of adult patients with cancer treated with interferon alfa-2a at dosages of 5 to 18 million U/m 2 per day. [25][26][27][28][29][30] These central nervous system effects are presumably due to induced toxic proteins, such as cytokines (eg, interleukin 1). 24 Kemeny et al 25 reported that of 38 patients receiving a combination of interferon alfa-2a and fluorouracil for advanced colorectal cancer, 34% developed gait abnormalities and 16% displayed memory disturbances.…”

Feasibility of prolonged use of interferon‐α in metastatic kidney carcinoma

“…1,5,7,17 Interferon-␣ has been as effective as a single agent or in combinations with interleukin-2, 8,14 vinblastine, 18 -20 and 5-fluorouracil. 21,22 The response rates have varied from 10% to 40%, most often from 15% to 20%.…”

“…4 -6 The average response rate to the most effective treatments of metastatic RCC rarely exceeds 20%. 5,7 Immunotherapy with interleukin-2 and/or interferon (IFN)-␣ currently is regarded as the most effective therapy for metastatic RCC, 5,8 -11 whereas only a few patients have responded to IFN-␤ or INF-␥. [12][13][14] Therefore, an appropriate approach to the treatment of patients with RCC outside of clinical studies is to use interferon-␣ or interleukin-2 alone or a combination of low-dose interleukin-2 and interferon-␣.…”