Phase I study of 5-fluorouracil with folinic acid combined with recombinant human granulocyte-macrophage colony-stimulating factor

Am J Clin Oncol. 1992 Dec;15(6):464-6. doi: 10.1097/00000421-199212000-00002.

Abstract

A Phase I study was conducted to determine whether the addition of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) to a combined 5-fluorouracil (5-FU) and folinic acid (FA) regimen would allow an escalated starting dose of 5-FU. FA (500 mg/m2) was administered as a 2-hour infusion on days 1 through 5, with 5-FU administered as a bolus injection 1 hour after the initiation of FA. Fifteen patients were enrolled in the trial; six were entered at a dose level of 375 mg/m2 of 5-FU, six at 450 mg/m2, and three at 540 mg/m2. rhGM-CSF was administered subcutaneously on days 6 through 15. A course of therapy was repeated every 28 days. Serious toxicity was observed at 450 mg/m2, with two patients developing grade 3 mucositis and one, grade 4 mucositis. Dose-limiting toxicity occurred at 540 mg/m2, at which point three patients developed grade 4 mucositis. One patient with metastatic colon cancer who received 5-FU at 540 mg/m2 achieved a partial response. Because of this persistent mucositis, the addition of rhGM-CSF used in this schedule would not allow an increased starting dose of 5-FU.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Controlled Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / therapy
  • Chemotherapy, Adjuvant
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / therapy
  • Dose-Response Relationship, Drug
  • Female
  • Fluorouracil / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Leucovorin / administration & dosage
  • Male
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / therapy
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / therapy
  • Recombinant Proteins / therapeutic use

Substances

  • Recombinant Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor
  • Leucovorin
  • Fluorouracil