title: Clinical activity of a cytotoxic fusion protein in the treatment of cutaneous T-cell lymphoma.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  The growth factor-cytotoxin fusion protein DAB486IL-2 demonstrated significant clinical activity with acceptable toxicity in a group of heavily pretreated patients with CTCL.
authors.affiliation: Evans Memorial Department of Clinical Research, Boston University Medical Center, MA.
authors.forename: P
authors.initials: P
authors.lastname: Hesketh
authors.forename: P
authors.initials: P
authors.lastname: Caguioa
authors.forename: H
authors.initials: H
authors.lastname: Koh
authors.forename: H
authors.initials: H
authors.lastname: Dewey
authors.forename: A
authors.initials: A
authors.lastname: Facada
authors.forename: R
authors.initials: R
authors.lastname: McCaffrey
authors.forename: K
authors.initials: K
authors.lastname: Parker
authors.forename: P
authors.initials: P
authors.lastname: Nylen
authors.forename: T
authors.initials: T
authors.lastname: Woodworth
mesh_terms: D004167:Diphtheria Toxin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016410:Lymphoma, T-Cell, Cutaneous / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D016896:Treatment Outcome
chemical_list: C054780:DAB(486)-interleukin 2; D004167:Diphtheria Toxin; D007376:Interleukin-2; D011993:Recombinant Fusion Proteins