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

Citation
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
ISSN journal
10675582
Volume
13
Issue
4
Year of publication
1993
Pages
267 - 274
Database
ISI
SICI code
1067-5582(1993)13:4<267:PTORGC>2.0.ZU;2-O
Abstract
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.