Comparison of a standard regimen (CHOP) with three intensive chemotherapy regimens for advanced non-Hodgkin's lymphoma.
BACKGROUND
CHOP is a first-generation, combination-chemotherapy regimen consisting of cyclophosphamide, doxorubicin, vincristine, and prednisone that has cured approximately 30 percent of patients with advanced stages of intermediate-grade or high-grade non-Hodgkin's lymphoma in national cooperative-group trials. However, studies at single institutions have suggested that 55 to 65 percent of such patients might be cured by third-generation regimens such as ones consisting of low-dose methotrexate with leucovorin rescue, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone (m-BACOD); prednisone, doxorubicin, cyclophosphamide, and etoposide, followed by cytarabine, bleomycin, vincristine, and methotrexate with leucovorin rescue (ProMACE-CytaBOM); and methotrexate with leucovorin rescue, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (MACOP-B).


METHODS
To make a valid comparison of these regimens, the Southwest Oncology Group and the Eastern Cooperative Oncology Group initiated a prospective, randomized phase III trial. The study end points were the response rate, time to treatment failure, overall survival, and incidence of severe or life-threatening toxicity. Dose intensity was calculated and analyzed.


RESULTS
Of the 1138 patients registered for the trial, 899 were eligible. Each treatment group contained at least 218 patients. Known prognostic factors were equally distributed among the groups. There were no significant differences among the groups in the rates of partial and complete response. At three years, 44 percent of all patients were alive without disease; there were no significant differences between the groups (41 percent in the CHOP and MACOP-B groups and 46 percent in the m-BACOD and ProMACE-CytaBOM groups; P = 0.35). Overall survival at three years was 52 percent (50 percent in the ProMACE-CytaBOM and MACOP-B groups, 52 percent in the m-BACOD group, and 54 percent in the CHOP group; P = 0.90). There was no subgroup of patients in which survival was improved by a third-generation regimen. Fatal toxic reactions occurred in 1 percent of the CHOP group, 3 percent of the ProMACE-CytaBOM group, 5 percent of the m-BACOD group, and 6 percent of the MACOP-B group (P = 0.09).


CONCLUSIONS
CHOP remains the best available treatment for patients with advanced-stage intermediate-grade or high-grade non-Hodgkin's lymphoma.
Fisher
R I
RI
Stritch School of Medicine, Loyola University, Maywood, Ill.
Gaynor
E R
ER
Dahlberg
S
S
Oken
M M
MM
Grogan
T M
TM
Mize
E M
EM
Glick
J H
JH
Coltman
C A
CA
Miller
T P
TP
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003561:Cytarabine / Q000008:administration & dosage; D003907:Dexamethasone / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality; D008727:Methotrexate / Q000008:administration & dosage; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage / Q000009:adverse effects
D003561:Cytarabine; D001761:Bleomycin; D014750:Vincristine; D005047:Etoposide; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D002955:Leucovorin; D011241:Prednisone; D008727:Methotrexate