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Interferon‐α and interleukin‐2 in the treatment of metastatic melanoma. Comparison of two phase II trials
Author(s) -
Keilholz Ulrich,
Scheibenbogen Carmen,
Tilgen Wolfgang,
Bergmann Lothar,
Weidmann Eckardt,
Seither Evi,
Richter Max,
Brado Bernadett,
Mitrou Paris S.,
Hunstein Werner
Publication year - 1993
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19930715)72:2<607::aid-cncr2820720245>3.0.co;2-r
Subject(s) - medicine , dosing , toxicity , regimen , alpha interferon , melanoma , confidence interval , schedule , immunotherapy , gastroenterology , interferon , pharmacology , immunology , cancer , cancer research , computer science , operating system
Background . Interferon‐α (IFNα) and interleukin‐2 (IL‐2) are active agents against malignant melanoma. There is, however, no consensus on the optimal dosing schedule of both drugs. This is a report of two sequential immunotherapy trials in patients with metastatic melanoma using two different IL‐2 dosing schedules. Methods . Schedule A consists of IFNα, 10 million U/m 2 /day subcutaneously for 5 days, followed by continuous intravenous infusion of IL‐2, 1 mg/m 2 /24 hours for 5 days. Schedule B consists of the same dose of IFNα, but a modified regimen of IL‐2. To improve the induction of high‐affinity IL‐2 receptors, the initial IL‐2 dose was increased (1 mg/m 2 /6 hours, followed by 1 mg/m 2 /12 hours, and 1 mg/m 2 /24 hours). To reduce toxicity, the dose was reduced thereafter to 0.25 mg/m 2 /24 hours for the following 3 days. Both regimens were repeated after 4 weeks. Results . 27 patients were treated with schedule A with a response rate of 18% (1 complete response [CR], 4 partial responses [PR]), 95% confidence interval, 6–36%. The response rate in 27 patients treated with schedule B was 41% (3 CR, 8 PR), 95% confidence interval 22–61%. Severe, often dose‐limiting toxicity was associated with IL‐2 in schedule A, particularly hypotension and fluid retention. Toxicity was reduced significantly in schedule B. Maximal serum levels of soluble CD25 were 17,022 ± 13,070 U/ml in schedule A, and 31,148 ± 4227 U/ml in schedule B ( P ± 0.01). Serum levels of TNFα were significantly lower in schedule B than in schedule A, as were the side effects. Conclusions . Toxicity of IL‐2 is reduced by modifying the schedule of administration, which also enhances the immunologic response and appears to increase the response rate.