A phase I study of yeast-derived recombinant human granulocyte-macrophage colony stimulating factor(rhGM-CSF) was undertaken in 27 patients with advanced malignancy. rhGM-CSF was administered once daily by subcutaneous(SC) injection(10 to
500μg/㎡/day)
for 10 days.
In present study, the maximum tolerated dose(MTD) was not reached up to the dose 500μg/㎡/day, but the dose-dependent increment of circulating granulocytes has been demonstrated and a plateau of hematologic effect was observed at rhGM-CSF dose
in
the
range of 150 to 350μg/㎡/day. The most common adverse drug events were fever(41%), bone pain/myalgia(26%), and skin rash(15%), but they were mild and well tolerated. Following a single SC injection at dosage levels of 50 to 500μg/㎡day,
detectable
serum levels occured within 30 minutes, peaked at 3.1±3.1 hours(mean±SD) and peak concentration were positively associated with dosage, followed by a rapid decrease occurring with a half life of 1.7±0.6(mean±SD).
Further studies will determine the impact on infection, morbidity, and mortality in patients who receive intensive anti-cancer chemotherapy. The optimal dose level of rhGM-CSF to be used in phaseⅡstudy is suggested to be in the range of 150 to
350μg/㎡/day.
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