Dose escalation of high-dose cyclophosphamide and etoposide with high-dose doxorubicin (CDE) and filgrastim for poor-risk non-Hodgkin's lymphoma

Abstract

Purpose: To identify the highest possible dose of cyclophosphamide (C) and etoposide (E) to be given with high-dose doxorubicin (D) and filgrastim (G-CSF) but without stem cell support in high-risk non-Hodgkin's lymphoma. Patients and methods: High-dose CDE was given to 18 evaluable patients, 5 had previous chemotherapy. All patients received D 90 mg/sqm and G-CSF 20 μg/kg/day. The first cohort had C 1800 mg/sqm and E 450 mg/sqm. Chemotherapy was given in equally divided doses over three days. Dose escalation was performed thrice up to C 3900 mg/sqm and E 975 mg/sqm. One to four courses were given. Results: The median number of days (quartile values) with neutrophils <0.5 × 109/l was 9 days (7-10), untransfused platelets <20 × 109/l 6 days (3-7), fever ≥ 38.0°C 5 days (3-8), intravenous antibiotics 10 days (9-12), with packed red cell transfusion 1 day (0-2), and with platelet transfusion 2 days (1-3). Six patients had complete remission and 11 partial remission from first course. There was no difference in toxicity according to dose level. A second course was given to 15 patients, resulting in fewer days with neutropenia (mean 7.2), and intravenous antibiotics (mean 6.3). Mucositis was the main non-hematologic toxicity. Conclusions: Very high-dose CDE with G-CSF but without stem cell support is feasible as primary therapy. The toxicity was similar to that of standard autologous stem cell transplantation programs.