Phase 2 trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with poor-prognosis, intermediate-grade non-Hodgkin lymphoma

An Eastern Cooperative Oncology Group trial (E3493)

Joseph A. Sparano, Edie Weller, Tipu Nazeer, Thomas Habermann, Ann E. Traynor, Jane Manalo, Peter Cassileth

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

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/m 2 per day), doxorubicin (12.5 mg/m 2 per day), and etoposide (60 mg/m 2 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.

Original languageEnglish (US)
Pages (from-to)1634-1640
Number of pages7
JournalBlood
Volume100
Issue number5
StatePublished - Sep 1 2002

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Oncology
Etoposide
Non-Hodgkin's Lymphoma
Doxorubicin
Cyclophosphamide
Confidence Intervals
Survival
Toxicity
Hazards
Lymphoma
Therapeutics
Neutropenia
Proportional Hazards Models
Intravenous Infusions
Thrombocytopenia
Anemia
Survival Rate
Infection

ASJC Scopus subject areas

  • Hematology

Cite this

Phase 2 trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with poor-prognosis, intermediate-grade non-Hodgkin lymphoma : An Eastern Cooperative Oncology Group trial (E3493). / Sparano, Joseph A.; Weller, Edie; Nazeer, Tipu; Habermann, Thomas; Traynor, Ann E.; Manalo, Jane; Cassileth, Peter.

In: Blood, Vol. 100, No. 5, 01.09.2002, p. 1634-1640.

Research output: Contribution to journalArticle

Sparano, Joseph A. ; Weller, Edie ; Nazeer, Tipu ; Habermann, Thomas ; Traynor, Ann E. ; Manalo, Jane ; Cassileth, Peter. / Phase 2 trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with poor-prognosis, intermediate-grade non-Hodgkin lymphoma : An Eastern Cooperative Oncology Group trial (E3493). In: Blood. 2002 ; Vol. 100, No. 5. pp. 1634-1640.
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abstract = "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/m 2 per day), doxorubicin (12.5 mg/m 2 per day), and etoposide (60 mg/m 2 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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AU - Sparano, Joseph A.

AU - Weller, Edie

AU - Nazeer, Tipu

AU - Habermann, Thomas

AU - Traynor, Ann E.

AU - Manalo, Jane

AU - Cassileth, Peter

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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/m 2 per day), doxorubicin (12.5 mg/m 2 per day), and etoposide (60 mg/m 2 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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