A dose-escalation study of aerosolized sargramostim in the treatment of metastatic melanoma: an NCCTG Study

Am J Clin Oncol. 2008 Dec;31(6):573-9. doi: 10.1097/COC.0b013e318173a536.


Objectives: Early testing of aerosolized sargramostim therapy demonstrated anecdotal clinical responses in patients with metastatic melanoma associated with emergence of systemic antitumor immunity. To improve the clinical and immunologic efficacy of therapy without compromising patient safety, we performed a further dose escalation trial in patients with metastatic melanoma.

Methods: We conducted a dose-escalation clinical trial of HLA-A2 patients with metastatic melanoma to the lung treated with aerosolized granulocyte macrophage colony stimulating factor (GM-CSF) (500-2000 microg/dose, with increments of 250 microg/dose/cohort) twice/d on days 1 to 7 and 15 to 21 every 28 days until progression or severe toxicity to find a dose where a majority of patients develop antitumor immunity. Five patients were treated per each dose level. Clinical, immune, and safety parameters were examined.

Results: The study accrued 40 patients. Toxicity was acceptable. All doses levels were exhausted without identifying a dose of GM-CSF at which a majority of patients (> or =3 of 5) demonstrated significant up-regulation of antitumor immunity. Three of 16 patients who were tetramer positive for at least one melanoma antigen (eg, MART-1) pretreatment developed an immune response (IR) to different tumor antigens. Two of 9 patients who were tetramer negative to all melanoma antigens pretreatment developed an IR against gp100. The greatest changes in antitumor immunity occurred at the highest dose levels.

Conclusions: A dose of aerosolized GM-CSF capable of inducing antitumor immunity in the majority of patients was not reached. All tested doses were well tolerated. The greatest increase in antitumor T cell IRs was achieved at the highest doses of GM-CSF.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adult
  • Aerosols
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage*
  • HLA-A2 Antigen / immunology
  • Humans
  • Immunologic Factors / administration & dosage*
  • Immunophenotyping
  • Immunotherapy*
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology
  • Lung Neoplasms / secondary
  • MART-1 Antigen
  • Male
  • Maximum Tolerated Dose
  • Melanoma / drug therapy*
  • Melanoma / immunology
  • Melanoma / secondary
  • Middle Aged
  • Neoplasm Proteins / metabolism
  • Neoplasm Staging
  • Recombinant Proteins
  • T-Lymphocytes / immunology
  • T-Lymphocytes, Cytotoxic / immunology
  • Treatment Outcome


  • Aerosols
  • Antigens, Neoplasm
  • HLA-A2 Antigen
  • Immunologic Factors
  • MART-1 Antigen
  • MLANA protein, human
  • Neoplasm Proteins
  • Recombinant Proteins
  • sargramostim
  • Granulocyte-Macrophage Colony-Stimulating Factor