Dose-escalation study of CHOP with or without prophylactic G-CSF in aggressive non-Hodgkin's lymphoma

Background: CHOP is accepted as the gold standard for first line chemotherapy of aggressive non-Hodgkin's lymphoma (NHL). A dose-escalation study of CHOP was conducted to determine the maximal tolerated dose (MTD) and toxicity profile of CHOP at three-week intervals with or without prophylactic recombinant human granulocyte colony-stimulating factor (rHuG-CSF) in patients with aggressive NHL. Patients and methods: The doses of drugs were escalated from 50 mg/m(2) to 70 mg/m(2) for doxorubicin and from 750 mg/m(2) to 2250 mg/m(2) for cyclophosphamide, with conventional doses of vincristine and oral prednisolone. After the MTD was determined without rHuG-CSF, dose escalation was conducted with prophylactic rHuG-CSF. Results: Thirty-three patients with NHL were enrolled into the study. The MTD without prophylactic rHuG-CSF was 70 mg/m(2) of doxorubicin and 1250 mg/m(2) of cyclophosphamide, with neutropenia as a dose-limiting toxicity. The MTD with prophylactic rHuG-CSF was 70 mg/m(2) of doxorubicin and 2250 mg/m(2) of cyclophosphamide. The overall response rate was 100% (76% complete response and 24% partial response). Progression-free survival and overall survival at five years were 45% and 66%, respectively. Conclusions: Significant dose escalation of doxorubicin and cyclophosphamide was feasible with prophylactic rHuG-CSF. The efficacy of dose-escalated CHOP should be compared with that of standard CHOP.