TY - JOUR
T1 - Phase 2 trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with poor-prognosis, intermediate-grade non-Hodgkin lymphoma
T2 - An Eastern Cooperative Oncology Group trial (E3493)
AU - Sparano, Joseph A.
AU - Weller, Edie
AU - Nazeer, Tipu
AU - Habermann, Thomas
AU - Traynor, Ann E.
AU - Manalo, Jane
AU - Cassileth, Peter
PY - 2002/9/1
Y1 - 2002/9/1
N2 - Preclinical and clinical evidence suggest a potential advantage for infusional therapy in lymphoma. Sixty-two analyzable patients with predominantly intermediate-grade non-Hodgkin lymphoma received cyclophosphamide (200 mg/m2 per day), doxorubicin (12.5 mg/m2 per day), and etoposide (60 mg/m2 per day) (CDE) by continuous intravenous infusion for 4 days (96 hours) every 3 weeks for a maximum of 8 cycles. By the age-adjusted International Prognostic Index (IPI), 42% were at high risk and 58% were at high-intermediate risk. Complete response (CR) occurred in 30 (48%) patients (95% confidence interval [CI], 35%, 64%), and partial response occurred in 16 (26%) patients, yielding an overall response rate of 74% (95% CI, 62%, 84%). Failure-free survival (FFS) rates at 1 and 2 years were 55% (95% CI, 43%, 67%) and 50% (95% CI, 38%, 62%), respectively. When comparing the outcome for 62 patients receiving infusional CDE with historical data derived from 927 IPI-matched lymphoma patients using a Cox proportional hazards model, there was a nonsignificant trend favoring CDE in FFS (P= .12) and overall survival (P= .09). Severe or life-threatening toxicity included neutropenia (68%), anemia (57%), thrombocytopenia (44%), and infection (24%). Two patients (3%) died of treatment-related infectious complications. The primary end point of improving 1-year FFS from 55% to 70% was not achieved with infusional CDE given as initial therapy in patients with poor-risk intermediate-grade lymphoma. It is unlikely that infusional therapy as used in this study produces a 25% or greater relative improvement in FFS compared with standard therapy.
AB - Preclinical and clinical evidence suggest a potential advantage for infusional therapy in lymphoma. Sixty-two analyzable patients with predominantly intermediate-grade non-Hodgkin lymphoma received cyclophosphamide (200 mg/m2 per day), doxorubicin (12.5 mg/m2 per day), and etoposide (60 mg/m2 per day) (CDE) by continuous intravenous infusion for 4 days (96 hours) every 3 weeks for a maximum of 8 cycles. By the age-adjusted International Prognostic Index (IPI), 42% were at high risk and 58% were at high-intermediate risk. Complete response (CR) occurred in 30 (48%) patients (95% confidence interval [CI], 35%, 64%), and partial response occurred in 16 (26%) patients, yielding an overall response rate of 74% (95% CI, 62%, 84%). Failure-free survival (FFS) rates at 1 and 2 years were 55% (95% CI, 43%, 67%) and 50% (95% CI, 38%, 62%), respectively. When comparing the outcome for 62 patients receiving infusional CDE with historical data derived from 927 IPI-matched lymphoma patients using a Cox proportional hazards model, there was a nonsignificant trend favoring CDE in FFS (P= .12) and overall survival (P= .09). Severe or life-threatening toxicity included neutropenia (68%), anemia (57%), thrombocytopenia (44%), and infection (24%). Two patients (3%) died of treatment-related infectious complications. The primary end point of improving 1-year FFS from 55% to 70% was not achieved with infusional CDE given as initial therapy in patients with poor-risk intermediate-grade lymphoma. It is unlikely that infusional therapy as used in this study produces a 25% or greater relative improvement in FFS compared with standard therapy.
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U2 - 10.1182/blood.v100.5.1634.h81702001634_1634_1640
DO - 10.1182/blood.v100.5.1634.h81702001634_1634_1640
M3 - Article
C2 - 12176882
AN - SCOPUS:0036720778
SN - 0006-4971
VL - 100
SP - 1634
EP - 1640
JO - Blood
JF - Blood
IS - 5
ER -