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 soft tissue sarcomas and since doxorubicin dose intensity may be compromised in combination chemotherapy, we evaluated the use of recombinant granulocytemacrophage colony-stimulating factor (rGM-CSF) to ameliorate myelosuppression and allow doxorubicin dose escalation in a phase I trial utilizing the MAID combination [Mesna 2.5 g/m2/day x 4 days, Adriamycin (doxorubicin) 15 mg/m2/day x 4 days, ifosfamide 2.0 g/m2/day x 3 days, dacarbazine 250 mg/m2/day x 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 x 4 days (level 1), while the doxorubicin dose for the next 7 patients was escalated by 25% to 18.75 mg/m2/day x 4 days (level 2). rGM-CSF was given at 5 micrograms/kg/day, days 5-14. All patients experienced moderate to severe myelosuppression, with all patients at dose level 2 requiring doxorubicin dose reduction to dose level 1 or lower by their third course of treatment. rGM-CSF failed to allow sustained escalation of the doxorubicin dose in the MAID regimen.

Management of Advanced Adult Soft Tissue Sarcoma

“…Several groups have conducted phase I and II studies of high-dose anthracycline/IFOS combinations with or without DTIC, with response rates ranging from 31 to 67%. [52][53][54][55][56][57][58][59][60][61][62][63][64] Toxicities have been severe, particularly thrombocytopenia, and the neuro-and nephrotoxicities of IFOS. At these doses neutropenic fevers are common, for growth factors do not completely protect against myelosuppression.…”