Infusional cyclophosphamide, doxorubicin, and etoposide in relapsed and resistant non-Hodgkin's lymphoma: Evidence for a schedule-dependent effect favoring infusional administration of chemotherapy

Joseph A. Sparano, Peter H. Wiernik, Andrea Leaf, Janice P. Dutcher

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Abstract

Purpose: This study attempted to determine the efficacy of cyclophosphamide (C), doxorubicin (D), and etoposide (E) administered as a continuous intravenous (IV) infusion (infusional CDE) over 4 days in patients with relapsed or resistant non-Hodgkin's lymphoma (rNHL) and in patients with previously untreated (uNHL) who had poor prognostic features. Patients and Methods: Fifty-eight patients with rNHL and 10 patients with uNHL received infusional CDE every 28 or more days; all but one had intermediate- to high-grade histology. The cumulative doses of C, D, and E administered per treatment cycle were 750 mg/m2, 50 mg/m2, and 240 mg/m2, respectively. In the rNHL group, all patients had previously received C most (81%) had received D, and a minority (16%) had received E. Results: Objective response occurred in 30 patients with rNHL (52%; 95% confidence interval, 39% to 65%); 10 patients had a complete response (CR) (17%; 95% confidence interval, 7% to 27%). Eleven patients (19%) remain progression-free (median follow-up, 22 months; range, 10 + to 38 + ), and six patients (10%) are disease-free (median follow-up, 25 months; range, 10+ to 38 + ). Among 10 patients with uNHL, eight (80%) had a CR, and none have relapsed (median follow-up, 11 months; range, 9 + to 24 + ). Toxicity was primarily hematologic. Two treatment-related deaths (3%) occurred, both attributable to infection in the relapsed or resistant group. Conclusion: Infusional CDE produced a CR in substantial proportion of patients who had previously been exposed to at least two of the agents administered as an IV bolus, suggesting a schedule-dependent effect in favor of the infusional administration of certain cytotoxic agents in patients with lymphoid neoplasms. In addition, infusional CDE was effective and tolerable in patients with poor-prognosis NHL when used as initial therapy, and merits further study in that setting.

Original languageEnglish (US)
Pages (from-to)1071-1079
Number of pages9
JournalJournal of Clinical Oncology
Volume11
Issue number6
StatePublished - 1993

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Etoposide
Non-Hodgkin's Lymphoma
Doxorubicin
Cyclophosphamide
Appointments and Schedules
Drug Therapy
Confidence Intervals
Cytotoxins
Intravenous Infusions
Histology
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

@article{df84f31718b2435c81d348faf267d2e3,
title = "Infusional cyclophosphamide, doxorubicin, and etoposide in relapsed and resistant non-Hodgkin's lymphoma: Evidence for a schedule-dependent effect favoring infusional administration of chemotherapy",
abstract = "Purpose: This study attempted to determine the efficacy of cyclophosphamide (C), doxorubicin (D), and etoposide (E) administered as a continuous intravenous (IV) infusion (infusional CDE) over 4 days in patients with relapsed or resistant non-Hodgkin's lymphoma (rNHL) and in patients with previously untreated (uNHL) who had poor prognostic features. Patients and Methods: Fifty-eight patients with rNHL and 10 patients with uNHL received infusional CDE every 28 or more days; all but one had intermediate- to high-grade histology. The cumulative doses of C, D, and E administered per treatment cycle were 750 mg/m2, 50 mg/m2, and 240 mg/m2, respectively. In the rNHL group, all patients had previously received C most (81{\%}) had received D, and a minority (16{\%}) had received E. Results: Objective response occurred in 30 patients with rNHL (52{\%}; 95{\%} confidence interval, 39{\%} to 65{\%}); 10 patients had a complete response (CR) (17{\%}; 95{\%} confidence interval, 7{\%} to 27{\%}). Eleven patients (19{\%}) remain progression-free (median follow-up, 22 months; range, 10 + to 38 + ), and six patients (10{\%}) are disease-free (median follow-up, 25 months; range, 10+ to 38 + ). Among 10 patients with uNHL, eight (80{\%}) had a CR, and none have relapsed (median follow-up, 11 months; range, 9 + to 24 + ). Toxicity was primarily hematologic. Two treatment-related deaths (3{\%}) occurred, both attributable to infection in the relapsed or resistant group. Conclusion: Infusional CDE produced a CR in substantial proportion of patients who had previously been exposed to at least two of the agents administered as an IV bolus, suggesting a schedule-dependent effect in favor of the infusional administration of certain cytotoxic agents in patients with lymphoid neoplasms. In addition, infusional CDE was effective and tolerable in patients with poor-prognosis NHL when used as initial therapy, and merits further study in that setting.",
author = "Sparano, {Joseph A.} and Wiernik, {Peter H.} and Andrea Leaf and Dutcher, {Janice P.}",
year = "1993",
language = "English (US)",
volume = "11",
pages = "1071--1079",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "6",

}

TY - JOUR

T1 - Infusional cyclophosphamide, doxorubicin, and etoposide in relapsed and resistant non-Hodgkin's lymphoma

T2 - Evidence for a schedule-dependent effect favoring infusional administration of chemotherapy

AU - Sparano, Joseph A.

AU - Wiernik, Peter H.

AU - Leaf, Andrea

AU - Dutcher, Janice P.

PY - 1993

Y1 - 1993

N2 - Purpose: This study attempted to determine the efficacy of cyclophosphamide (C), doxorubicin (D), and etoposide (E) administered as a continuous intravenous (IV) infusion (infusional CDE) over 4 days in patients with relapsed or resistant non-Hodgkin's lymphoma (rNHL) and in patients with previously untreated (uNHL) who had poor prognostic features. Patients and Methods: Fifty-eight patients with rNHL and 10 patients with uNHL received infusional CDE every 28 or more days; all but one had intermediate- to high-grade histology. The cumulative doses of C, D, and E administered per treatment cycle were 750 mg/m2, 50 mg/m2, and 240 mg/m2, respectively. In the rNHL group, all patients had previously received C most (81%) had received D, and a minority (16%) had received E. Results: Objective response occurred in 30 patients with rNHL (52%; 95% confidence interval, 39% to 65%); 10 patients had a complete response (CR) (17%; 95% confidence interval, 7% to 27%). Eleven patients (19%) remain progression-free (median follow-up, 22 months; range, 10 + to 38 + ), and six patients (10%) are disease-free (median follow-up, 25 months; range, 10+ to 38 + ). Among 10 patients with uNHL, eight (80%) had a CR, and none have relapsed (median follow-up, 11 months; range, 9 + to 24 + ). Toxicity was primarily hematologic. Two treatment-related deaths (3%) occurred, both attributable to infection in the relapsed or resistant group. Conclusion: Infusional CDE produced a CR in substantial proportion of patients who had previously been exposed to at least two of the agents administered as an IV bolus, suggesting a schedule-dependent effect in favor of the infusional administration of certain cytotoxic agents in patients with lymphoid neoplasms. In addition, infusional CDE was effective and tolerable in patients with poor-prognosis NHL when used as initial therapy, and merits further study in that setting.

AB - Purpose: This study attempted to determine the efficacy of cyclophosphamide (C), doxorubicin (D), and etoposide (E) administered as a continuous intravenous (IV) infusion (infusional CDE) over 4 days in patients with relapsed or resistant non-Hodgkin's lymphoma (rNHL) and in patients with previously untreated (uNHL) who had poor prognostic features. Patients and Methods: Fifty-eight patients with rNHL and 10 patients with uNHL received infusional CDE every 28 or more days; all but one had intermediate- to high-grade histology. The cumulative doses of C, D, and E administered per treatment cycle were 750 mg/m2, 50 mg/m2, and 240 mg/m2, respectively. In the rNHL group, all patients had previously received C most (81%) had received D, and a minority (16%) had received E. Results: Objective response occurred in 30 patients with rNHL (52%; 95% confidence interval, 39% to 65%); 10 patients had a complete response (CR) (17%; 95% confidence interval, 7% to 27%). Eleven patients (19%) remain progression-free (median follow-up, 22 months; range, 10 + to 38 + ), and six patients (10%) are disease-free (median follow-up, 25 months; range, 10+ to 38 + ). Among 10 patients with uNHL, eight (80%) had a CR, and none have relapsed (median follow-up, 11 months; range, 9 + to 24 + ). Toxicity was primarily hematologic. Two treatment-related deaths (3%) occurred, both attributable to infection in the relapsed or resistant group. Conclusion: Infusional CDE produced a CR in substantial proportion of patients who had previously been exposed to at least two of the agents administered as an IV bolus, suggesting a schedule-dependent effect in favor of the infusional administration of certain cytotoxic agents in patients with lymphoid neoplasms. In addition, infusional CDE was effective and tolerable in patients with poor-prognosis NHL when used as initial therapy, and merits further study in that setting.

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