title: Phase I trial of inhaled natural interleukin 2 for treatment of pulmonary malignancy: toxicity, pharmacokinetics, and biological effects.
abstract: Safety, local and systemic immunomodulation, and tumor response to treatment with aerosolized natural interleukin 2 (nIL-2) applied five times a day were studied in a Phase I trial in 16 patients with pulmonary malignancies refractory to conventional therapy. The toxicity of inhaled nIL-2 was different from that observed after systemic administration. Reversible airway irritation causing a nonproductive cough represented the dose-limiting toxicity. Mild to moderate reduction of the vital capacity and forced expiratory volume (FEV1) with minor effects on relative FEV1, peak expiratory flow, airway resistance, and PaO2 was experienced by individual patients. In 14 patients suffering from pulmonary metastases due to renal cell cancer, one durable complete response, one partial response, and one mixed response were observed. Inhalation of nIL-2 aerosol resulted in a dose-dependent expansion of pulmonary immunocompetent cells in bronchoalveolar lavage fluid. Posttreatment bronchoalveolar lavage showed an activated lymphocyte phenotype with increased HLA-DR expression. The only systemic biological effect detectable in peripheral blood was a marked increase of soluble interleukin 2 receptor serum levels. We conclude that treatment with aerosolized nIL-2 is an effective means for site-specific immunomodulation and deserves further investigation for the treatment of malignant and inflammatory lung disease.
authors.affiliation: Second Medical Department, Kreiskrankenhaus Lüdenscheid and Third Medical Department, Hematology Branch, University Hospital, Mainz, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Lorenz
authors.forename: K
authors.initials: K
authors.lastname: Wilhelm
authors.forename: M
authors.initials: M
authors.lastname: Kessler
authors.forename: C
authors.initials: C
authors.lastname: Peschel
authors.forename: U
authors.initials: U
authors.lastname: Schwulera
authors.forename: R
authors.initials: R
authors.lastname: Lissner
authors.forename: W G
authors.initials: WG
authors.lastname: Struff
authors.forename: E
authors.initials: E
authors.lastname: Huland
authors.forename: C
authors.initials: C
authors.lastname: Huber
authors.forename: W E
authors.initials: WE
authors.lastname: Aulitzky
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D000336:Aerosols; D000368:Aged; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000628:therapy*; D008297:Male; D008875:Middle Aged
chemical_list: D000336:Aerosols; D007376:Interleukin-2