PHASE-I TRIAL OF RECOMBINANT GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN PATIENTS WITH LUNG-CANCER - CLINICAL AND IMMUNOLOGICAL EFFECTS

Recombinant granulocyte-macrophage colony-stimulating factor (rhuGM-CSF) may enhance the functional activity of monocytes and macrophages in vitro and in vivo and thereby have antitumor activity. A phase I trial using rhuGM-CSF was performed; the trial included 17 patients with unresectable and/or metastatic lung cancer. rhuGM-CSF was administered as a continuous infusion for 14 days at four dose levels: 60 mug/m2, 125 mug/m2, 250 mug/m2, and 500 mug/m2. Dose-limiting toxicity was pulmonary and occurred at 500 mug/m2, With the maximal tolerated dose (MTD) identified as 250 mug/m2. The hematologic effects of rhuGM-CSF included leukocytosis with significant correlations between dose level and the numbers of neutrophils, monocytes, eosinophils, and lymphocytes. Bronchoalveolar lavage was performed for 14 patients, and no effect on alveolar macrophage numbers was detected. Tumor biopsies were obtained in two patients, and no changes in macrophage infiltrates were detected with use of immunohistochemical studies. Serum levels of GM-CSF reached a steady state during week one and decreased or were undetectable during week two. No evidence of tumor regression was seen. rhuGM-CSF when administered as a continuous infusion was well tolerated and appears to modulate monocyte numbers and function in vivo.