SWOG 8825: Melphalan GM-CSF: A phase I study

The use of intravenous melphalan at higher doses is limited by severe myelosuppression. It was postulated that GM-CSF would permit the use of higher dose melphalan with only moderate myelosuppression easily manageable in an outpatient setting. Therefore, a phase I study of intravenous melphalan utilizing GM-CSF (recombinant granulocyte-macrophage colony-stimulating factor) support was initiated. Intravenous melphalan at doses of 15-45 mg/m² was administered every 28 days. GM-CSF was utilized at doses of 10-20 μg/kg/day subcutaneously Days 2-21 on a 28-day cycle. Twenty-five patients received 53 courses of therapy. The dose-limiting toxicities were severe or life-threatening granulocytopenia and thrombocytopenia. Utilizing 20 μg/kg/day GM-CSF, the maximum tolerated dose (MTD) of melphalan is 30 mg/m² and, with 10 mg/kg/day GM-CSF, the maximum tolerated melphalan dose is only 20 mg/m². One patient with ovarian cancer achieved a partial response. Because the reported MTD of intravenous melphalan without GM-CSF is 30 mg/m², GM-CSF has not allowed sufficient escalation of the intravenous melphalan dose for routine outpatient use.