title: A phase I study of prolonged continuous infusion of low dose recombinant interleukin-2 in melanoma and renal cell cancer. Part I: Clinical aspects.
abstract: The optimal schedule for recombinant interleukin-2 (rIL-2) administration is unclear. Because the clinical and immunological effects of prolonged continuous exposure to rIL-2 are unknown, we have conducted a phase I study to assess the toxicity and feasibility of continuous low dose infusion of rIL-2 (EuroCetus) using central venous access with a portable infusion device on an out-patient basis. Twenty-two patients entered the study, 13 with melanoma and nine with renal cell cancer, age range 26-66 years (median 51), performance status less than or equal to 1. They were treated with one of the following doses per m2 per 24 h: 0.18 x 10(6) IU, 0.6 x 10(6) IU, 1.8 x 10(6) IU, 3 x 10(6) IU, 6 x 10(6) IU and 9 x 10(6) IU. Toxicity was evaluable in 20 patients receiving greater than or equal to 3 weeks treatment duration or in whom treatment was discontinued prematurely because of toxicity. Constitutional symptoms consisting of fatigue, malaise and fever up to 40 degrees C without significant organ dysfunction occurred with doses greater than or equal to 1.8 x 10(6) IU m-2. The maximum tolerated dose was 6 x 10(6) IU m-2 24 h-1. In all patients toxicity reached a peak at 3 weeks and resolved thereafter despite continued rIL-2 treatment. Peripheral blood eosinophilia (up to 66% of white blood cell count) followed the same pattern. An infection of the central venous access occurred in 55% of the patients but this was mostly asymptomatic. Thirteen patients were treated greater than or equal to 6 weeks and were evaluable for tumour response. A partial remission occurred in a patient with melanoma with a dose of 1.8 x 10(6) IU rIL-2 m-2 24 h-1.
authors.affiliation: Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam.
authors.forename: L T
authors.initials: LT
authors.lastname: Vlasveld
authors.forename: E M
authors.initials: EM
authors.lastname: Rankin
authors.forename: A
authors.initials: A
authors.lastname: Hekman
authors.forename: S
authors.initials: S
authors.lastname: Rodenhuis
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: A M
authors.initials: AM
authors.lastname: Hilton
authors.forename: A C
authors.initials: AC
authors.lastname: Dubbelman
authors.forename: F A
authors.initials: FA
authors.lastname: Vyth-Dreese
authors.forename: C J
authors.initials: CJ
authors.lastname: Melief
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008545:Melanoma / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D008875:Middle Aged; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D007376:Interleukin-2; D011994:Recombinant Proteins