GM-CSF Did Not Allow Doxorubicin Dose Escalation in the MAID Regimen: A Phase I Trial. A Southwest Oncology Group Study

Abstract

Since dose intensity of doxorubicin is correlated with the clinical response of patients with sofl tissue sarcomas and since doxorubicin dose intensity niay be compromised in conibiiiation chemotherapy, we evaluated the use of recoinbinant granulocyte-macrophage colony-stiniulating factor (rGM-CSF) to ameliorate niyelosuppression and allow doxorubicin dose escalation in a phase I trial utilizing the MAID combination [Mesna 2.5 g/m²/day × 4 days, Adrianiyciii (doxorubicin) 15 mg/m²/day × 4 days, ifosfaniide 2.0 g/m²/day × 3 days, dacarbazine 250 mg/m²/day × 4 days; to be repeated every 21 days]. Thirteen patients were treated. The doxorubicin dose for the first 6 patients was at the standard dose of 15 mg/m²/day × 4 days (level I), while the doxorubicin dose for the next 7 patients was escalated by 25% to 18.75 mg/m²/day × 4 days (level 2). tGM-CSF was given at 5 μg/kg/day, days 5-14. All patients experienced moderate to severe tiyelosuppression, with all patients at dose level 2 requiring doxorubicin dose reduction to dose level I or lower by their third course of treatment. rGM-CSF failed to allow sustained escalation of the doxorubicin dose in the MAID reginien.