Aerosol granulocyte macrophage-colony stimulating factor: A low toxicity, lung-specific biological therapy in patients with lung metastases

Peter M. Anderson, Svetomir N. Markovic, Jeffery A. Sloan, Mary Lou Clawson, Mark Wylam, Carola A.S. Arndt, William A. Smithson, Patrick Burch, Michael Gornet, Emel Rahman

Research output: Contribution to journalArticle

109 Scopus citations

Abstract

The objective was to study the feasibility of granulocyte macrophage- colony stimulating factor (GM-CSF) delivery to the lung using an aerosol in humans. A Phase I dose escalation study provided GM-CSF at three dose levels as a twice-a-day (BID) x 7 days schedule. Pulmonary functions were monitored using a remote spirometry device. Blood counts were checked at the beginning and end of each week of GM-CSF nebulization. If no toxicity was encountered, patients rested for 7 days and then were treated at the next dose level. Six of seven patients were successfully dose escalated from 60 μg/dose BID x 7 days, to 120 μg/dose BID x 7 days, then 240 μg/dose BID x 7 days. No toxicity was seen. Comparison of day 0 and day 7 blood leukocyte counts showed no significant increases in either leukocyte numbers or percentage of neutrophils. Pulmonary functions test changes were minor. No significant change in forced vital capacity, FEV1, peak flow, or FEF 25-75 related to either time or dose level was observed. One patient's lung metastases progressed. The other five patients received an additional 2-6 months of intermittent aerosol GM-CSF at dose level 3 without side effects. One patient with Ewing's sarcoma has a complete response, and a patient with melanoma had a partial response; the other three had stabilization of pulmonary metastases for 2-6 months. Aerosol delivery of GM-CSF is feasible, safe, and possibly effective. Aerosol cytokine delivery may achieve effective immunological activation against cancer in the lung and is worthy of further study.

Original languageEnglish (US)
Pages (from-to)2316-2323
Number of pages8
JournalClinical Cancer Research
Volume5
Issue number9
StatePublished - Sep 1 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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