Phase I trial of infusional cyclophosphamide, doxorubicin, and etoposide plus granulocyte-macrophage colony stimulating factor (GM-CSF) in non-Hodgkin's lymphoma.

PURPOSE: To determine the recommended phase II dose (RPTD) of a 96-h continuous intravenous infusion (CIVI) of cyclophosphamide (200, 300, or 400 mg/m2/d) and etoposide (60 or 90 mg/m2/d) when used in conjunction with doxorubicin (12.5 mg/m2/d) (CDE) given every 28 d plus granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with poor prognosis non-Hodgkin's lymphoma (Group A), and the same regimen given every 21 d (Group B).
METHODS: In Group A, infusional CDE was repeated every 28 d, GM-CSF (250 microg/m2) was given subcutaneously from d 6 until neutrophil recovery, with dose escalation in cohorts of three to six evaluable patients. The RPTD of cyclophosphamide and etoposide established in Group A was then used with CDE given every 3 wk (Group B) with GM-CSF given on d 6-20, and dose escalation was attempted again.
RESULTS: In Group A, the RPTD of cyclophosphamide and etoposide were 300 mg/m2/d and 90 mg/m2/d, respectively; prolonged neutropenia was the dose-limiting toxicity. In Group B, use of GM-CSF on d 6-20 did not facilitate dose escalation above the RPTD established in Group A. Complete response occurred in 13/26 patients (50%) with no prior chemotherapy, and in 4/16 patients (25%) who had relapsed after prior chemotherapy.
CONCLUSIONS: Because of the increase in dose and dose-density afforded by the administration of GM-CSF, the relative dose intensity was increased by twofold for cyclophosphamide (400 vs 200 mg/m2/wk) and etoposide (120 vs 60 mg/m2/wk), and by 1.3-fold for doxorubicin (16.7 vs 12.5 mg/m2/wk).

RCT Entities:   Population Interventions Outcomes