[Phase I trial of recombinant human granulocyte-macrophage colony stimulating factor. Results in patients with advanced tumors]

Bull Cancer. 1993 May;80(5):418-30.
[Article in French]

Abstract

Fourteen patients with advanced solid tumors were included in a phase I trial of recombinant human E coli derived granulocyte-macrophage colony-stimulating factor (GM-CSF) given daily subcutaneously for 10 consecutive days. Dose levels were increased from 250 micrograms/m2 to 500, 750 and 1,000 micrograms/m2. Adverse effects were mainly fever, local irritation, lethargia, arthalgia. Three patients did not complete the 10-day cycle: one patient died due to progressive disease without toxic effects related to GM-CSF, one was withdrawn because of suspicion of pulmonary embolism (not confirmed), one patient had hypotension, not recurring after treatment with GM-CSF. Although the maximum tolerated dose was not reached, the trial was stopped at 1,000 micrograms/m2, considering the satisfactory response and the high white blood cell counts observed with lower dose levels. N-fold increases of leucocyte count ranged between 4.2 and 8.2 for the first dose level (250 micrograms/m2), 4 and 10.1 for 500 micrograms/m2, 8.5 and 12.3 for 750 micrograms/m2 and 5.6 and 8.3 for 1,000 micrograms/m2. Increases of granulocyte, neutrophil and eosinophil counts had a similar pattern with a weaker response at 1,000 micrograms/m2 (two patients who completed the cycle). In contrast, even for the first three levels, no dose response relationship was shown for increases of monocytes (between 2.8 and 12 n-fold whatever the dose), or lymphocytes (between 1.7 and 10.7 n-fold whatever the dose). Decreases of platelets (between 6 and 55%) were observed, followed by a rebound after stopping treatment. No modifications of erythrocyte count were observed. Subcutaneous GM-CSF was well-tolerated up to 1,000 micrograms/m2 during a 10-day course. Hematological effects were observed from the first dose level of 250 micrograms/m2.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • English Abstract
  • Randomized Controlled Trial

MeSH terms

  • Drug Tolerance
  • Eosinophils
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Leukocyte Count
  • Monocytes
  • Neoplasms / blood
  • Neoplasms / therapy*
  • Neutrophils
  • Platelet Count

Substances

  • Granulocyte-Macrophage Colony-Stimulating Factor