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

Ann Oncol. 1996 Dec;7(10):1037-41. doi: 10.1093/oxfordjournals.annonc.a010496.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / adverse effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Drug Administration Schedule
  • Etoposide / administration & dosage
  • Etoposide / adverse effects
  • Female
  • Filgrastim
  • Granulocyte Colony-Stimulating Factor / administration & dosage*
  • Humans
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Male
  • Middle Aged
  • Recombinant Proteins

Substances

  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Etoposide
  • Doxorubicin
  • Cyclophosphamide
  • Filgrastim

Supplementary concepts

  • ACE protocol 1