The lung is a common site of both metastases and primary neoplasia. This phase I study was designed to test the feasibility and toxicity of administering interleukin (IL)-2 liposomes by aerosol to patients with pulmonary metastases. The goal was to test whether IL-2 liposomes could be given by aerosol using biologically effective but non-toxic doses in an outpatient setting. Liposomes containing IL-2 or placebo (buffer) were synthesized and mixed to provide a constant lipid dose, and were nebulized using a Puritan twin jet nebulizer and a standard compressor. The liposome-containing mist was inhaled for about 20 min 3 times a day in order to selectively stimulate immune function within the lung and to avoid systemic toxicity. The dose chosen was based on canine efficacy and toxicity studies that used bronchoalveolar lavage to demonstrate increased cell numbers and activation of mononuclear cells after inhalation of nebulized IL-2 liposomes. Nine patients were treated in three cohorts of three patients at 1.5, 3.0 and 6.0 x 106 IU of IL-2 3 times a day. No significant toxicity was observed. We conclude that the delivery of IL-2 liposomes by inhalation is well tolerated. Further studies of inhalational IL-2 liposomes to determine efficacy as an anti-cancer therapy are warranted. (C) 2000 Lippincott Williams and Wilkins.