Phase I study of 5-fluorouracil with folinic acid combined with recombinant human granulocyte-macrophage...

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.