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


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 micrograms/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 x 10(9)/l was 9 days (7-10), untransfused platelets < 20 x 10(9)/l 6 days (3-7), fever > or = 38 degrees 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.
Juliusson
G
G
Department of Hematology, University Hospital, Linköping, Sweden.
Liliemark
J
J
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004334:Drug Administration Schedule; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D000069585:Filgrastim; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins
D011994:Recombinant Proteins; D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D004317:Doxorubicin; D003520:Cyclophosphamide; D000069585:Filgrastim