Interferon-alpha and interleukin-2 in the treatment of metastatic melanoma. Comparison of two phase II trials

Cancer. 1993 Jul 15;72(2):607-14. doi: 10.1002/1097-0142(19930715)72:2<607::aid-cncr2820720245>;2-r.


Background: Interferon-alpha (IFN alpha) 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 IFN alpha, 10 million U/m2/day subcutaneously for 5 days, followed by continuous intravenous infusion of IL-2, 1 mg/m2/24 hours for 5 days. Schedule B consists of the same dose of IFN alpha, 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/m2/6 hours, followed by 1 mg/m2/12 hours, and 1 mg/m2/24 hours). To reduce toxicity, the dose was reduced thereafter to 0.25 mg/m2/24 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 < or = 0.01). Serum levels of TNF alpha 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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Drug Administration Schedule
  • Female
  • Humans
  • Hypotension / etiology
  • Interferon-alpha / therapeutic use*
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / adverse effects
  • Interleukin-2 / therapeutic use*
  • Male
  • Melanoma / drug therapy*
  • Middle Aged
  • Neoplasm Metastasis
  • Receptors, Interleukin-2 / analysis
  • Skin Neoplasms / drug therapy*
  • Treatment Outcome


  • Interferon-alpha
  • Interleukin-2
  • Receptors, Interleukin-2