Rm. Bukowski et al., PHASE-I TRIAL OF RECOMBINANT GRANULOCYTE-MACROPHAGE COLONY-STIMULATING FACTOR IN PATIENTS WITH LUNG-CANCER - CLINICAL AND IMMUNOLOGICAL EFFECTS, Journal of immunotherapy with emphasis on tumor immunology, 13(4), 1993, pp. 267-274
Citations number
32
Categorie Soggetti
Immunology,Oncology,"Medicine, Research & Experimental
Recombinant granulocyte-macrophage colony-stimulating factor (rhuGM-CS
F) may enhance the functional activity of monocytes and macrophages in
vitro and in vivo and thereby have antitumor activity. A phase I tria
l using rhuGM-CSF was performed; the trial included 17 patients with u
nresectable and/or metastatic lung cancer. rhuGM-CSF was administered
as a continuous infusion for 14 days at four dose levels: 60 mug/m2, 1
25 mug/m2, 250 mug/m2, and 500 mug/m2. Dose-limiting toxicity was pulm
onary and occurred at 500 mug/m2, With the maximal tolerated dose (MTD
) identified as 250 mug/m2. The hematologic effects of rhuGM-CSF inclu
ded leukocytosis with significant correlations between dose level and
the numbers of neutrophils, monocytes, eosinophils, and lymphocytes. B
ronchoalveolar 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 detect
ed with use of immunohistochemical studies. Serum levels of GM-CSF rea
ched 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 appe
ars to modulate monocyte numbers and function in vivo.