Clinical activity of a cytotoxic fusion protein in the treatment of cutaneous T-cell lymphoma

J Clin Oncol. 1993 Sep;11(9):1682-90. doi: 10.1200/JCO.1993.11.9.1682.

Abstract

Purpose: A phase I trial in patients with refractory hematologic malignancies was performed at our institution to test the clinical relevance of the selective cytotoxic activity of the interleukin-2 (IL-2)-diphtheria toxin fusion protein, DAB486IL-2. A subset of five patients from this trial, all with cutaneous T-cell lymphomas (CTCL), forms the basis of this report.

Patients and methods: Two treatment schedules were used. One patient received DAB486IL-2 at a dose of 0.075 mg/kg/d intravenous (i.v.) bolus over 15 minutes daily for 5 consecutive days. The other four patients received DAB486IL-2 at a dose of 0.1 mg/kg as an i.v. infusion over 180 minutes weekly for 5 consecutive weeks.

Results: Three of the five CTCL patients achieved significant tumor responses. One patient attained a complete clinical and pathologic response (CR), which has been sustained without any interval treatment for 33+ months. Two other patients achieved partial responses (PRs) of 17+ and 4 months' duration, respectively. Treatment was well tolerated. The most common adverse effect was a transient increase in hepatic transaminases experienced by all five patients.

Conclusion: The growth factor-cytotoxin fusion protein DAB486IL-2 demonstrated significant clinical activity with acceptable toxicity in a group of heavily pretreated patients with CTCL.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diphtheria Toxin / administration & dosage
  • Diphtheria Toxin / pharmacokinetics
  • Diphtheria Toxin / therapeutic use*
  • Drug Administration Schedule
  • Humans
  • Infusions, Intravenous
  • Injections, Intravenous
  • Interleukin-2 / administration & dosage
  • Interleukin-2 / pharmacokinetics
  • Interleukin-2 / therapeutic use*
  • Lymphoma, T-Cell, Cutaneous / blood
  • Lymphoma, T-Cell, Cutaneous / drug therapy*
  • Lymphoma, T-Cell, Cutaneous / immunology
  • Male
  • Middle Aged
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / pharmacokinetics
  • Recombinant Fusion Proteins / therapeutic use
  • Skin Neoplasms / blood
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / immunology
  • Treatment Outcome

Substances

  • DAB(486)-interleukin 2
  • Diphtheria Toxin
  • Interleukin-2
  • Recombinant Fusion Proteins