Ifosfamide, carboplatin, and etoposide: a highly effective cytoreduction and peripheral-blood progenitor-cell mobilization regimen for transplant-eligible patients with non-Hodgkin's lymphoma.
OBJECTIVE
To evaluate a chemotherapy regimen that consisted of ifosfamide administered as an infusion with bolus carboplatin, and etoposide (ICE) supported by granulocyte colony-stimulating factor (G-CSF) for cytoreduction and stem-cell mobilization in transplant-eligible patients with primary refractory or relapsed non-Hodgkin's lymphoma (NHL).


METHODS
One hundred sixty-three transplant-eligible patients with relapsed or primary refractory NHL were treated from October 1993 to December 1997 with ICE chemotherapy at Memorial Sloan-Kettering Cancer Center. Administration of three cycles of ICE chemotherapy was planned at 2-week intervals. Peripheral-blood progenitor cells were collected after cycle 3, and all patients who achieved a partial response (PR) or complete response (CR) to ICE chemotherapy were eligible to proceed to transplantation. Event-free and overall survival, ICE-related toxicity, and the number of CD34(+) cells collected after treatment with ICE and G-CSF were evaluated.


RESULTS
All 163 patients were assessable for response, and there was no treatment-related mortality. A major response (CR/PR) was evident in 108 patients (66.3%); 89% of the responding patients underwent successful transplantation. Patient who underwent transplantation and achieved a CR to ICE had a superior overall survival to that of patients who achieved a PR (65% v 30%; P =.003). The median number of CD34(+) cells/kg collected was 8.4 x 10(6). The dose-limiting toxicity of ICE was hematologic, with 29.4% of patients developing grade 3/4 thrombocytopenia. There were minimal nonhematologic side effects.


CONCLUSIONS
ICE chemotherapy, with ifosfamide administered as a 24-hour infusion to decrease CNS side effects, and the substitution of carboplatin for cisplatin to minimize nephrotoxicity, is a very effective cytoreduction and mobilization regimen in patients with NHL. Furthermore, the quality of the clinical response to ICE predicts for posttransplant outcome.
Moskowitz
C H
CH
Lymphoma and Hematology Services, Department of Medicine, and Departments of Radiotherapy, Pathology, and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. amoskowiz@mskcc.org
Bertino
J R
JR
Glassman
J R
JR
Hedrick
E E
EE
Hunte
S
S
Coady-Lyons
N
N
Agus
D B
DB
Goy
A
A
Jurcic
J
J
Noy
A
A
O'Brien
J
J
Portlock
C S
CS
Straus
D S
DS
Childs
B
B
Frank
R
R
Yahalom
J
J
Filippa
D
D
Louie
D
D
Nimer
S D
SD
Zelenetz
A D
AD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002465:Cell Movement; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013234:Stem Cells / Q000502:physiology
D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D016190:Carboplatin; D007069:Ifosfamide