A retrospective comparison of three sequential groups of patients with recurrent/refractory chronic lymphocytic leukemia treated with fludarabine-based regimens

William Wierda, Susan O'Brien, Stefan Faderl, Alessandra Ferrajoli, Xuemei Wang, Kim Anh Do, Guillermo Garcia-Manero, Deborah Thomas, Jorge Cortes, Farhad Ravandi-Kashani, Francis Giles, Susan Lerner, Happ Kantarjian, Michael Keating

Research output: Contribution to journalArticle

Abstract

BACKGROUND. Combining therapeutics with single-agent activity has improved treatment for patients with many malignancies. Debate continues about the impact of treatment on survival in patients with chronic lymphocytic leukemia (CLL). Purine analogues are the most active agents for treatment of patients with CLL. Recently, it was shown that a chemoimmunotherapy regimen combining fludarabine (F), cyclophosphamide (C), and rituximab (R) (FCR) was very effective in treating patients with recurrent and/or refractory CLL. The objective of the current analysis was to determine whether improvements in treatment have had an impact on survival for patients with CLL. METHODS. Three nonoverlapping, sequential groups of patients enrolled on Phase II studies who received treatment with F (n = 251 patients), FC (n = 111 patients), or FCR (n = 143 patients) were analyzed. Pretreatment characteristics, responses to treatment, and overall survival were compared. RESULTS. Patients who were treated with FCR had a higher complete remission rate compared with patients who were treated with combined F and C or with F alone. Statistically significantly longer estimated median survival was noted for patients who received FCR. A Cox proportional hazards, multivariable model for overall survival that included all patients (n = 505) showed that patients who received FCR had longer survival (P < 0.0001) after adjusting for other significant (P < 0.05) pretreatment characteristics, including age, hemoglobin, β-2 microglobulin, and the number of prior treatments. CONCLUSIONS. The results of this retrospective comparison of patients with recurrent and refractory CLL indicated a higher complete remission rate and the longest estimated survival for patients who were treated with FCR, providing the basis for randomized clinical trials of this regimen.

Original languageEnglish (US)
Pages (from-to)337-345
Number of pages9
JournalCancer
Volume106
Issue number2
DOIs
StatePublished - Jan 15 2006
Externally publishedYes

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B-Cell Chronic Lymphocytic Leukemia
Survival
fludarabine
Therapeutics
Proxy
Proportional Hazards Models
Cyclophosphamide
Hemoglobins

Keywords

  • Chronic lymphocytic leukemia
  • Cyclophosphamide
  • Fludarabine
  • Rituximab
  • Salvage
  • Treatment

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

A retrospective comparison of three sequential groups of patients with recurrent/refractory chronic lymphocytic leukemia treated with fludarabine-based regimens. / Wierda, William; O'Brien, Susan; Faderl, Stefan; Ferrajoli, Alessandra; Wang, Xuemei; Do, Kim Anh; Garcia-Manero, Guillermo; Thomas, Deborah; Cortes, Jorge; Ravandi-Kashani, Farhad; Giles, Francis; Lerner, Susan; Kantarjian, Happ; Keating, Michael.

In: Cancer, Vol. 106, No. 2, 15.01.2006, p. 337-345.

Research output: Contribution to journalArticle

Wierda, W, O'Brien, S, Faderl, S, Ferrajoli, A, Wang, X, Do, KA, Garcia-Manero, G, Thomas, D, Cortes, J, Ravandi-Kashani, F, Giles, F, Lerner, S, Kantarjian, H & Keating, M 2006, 'A retrospective comparison of three sequential groups of patients with recurrent/refractory chronic lymphocytic leukemia treated with fludarabine-based regimens', Cancer, vol. 106, no. 2, pp. 337-345. https://doi.org/10.1002/cncr.21554
Wierda, William ; O'Brien, Susan ; Faderl, Stefan ; Ferrajoli, Alessandra ; Wang, Xuemei ; Do, Kim Anh ; Garcia-Manero, Guillermo ; Thomas, Deborah ; Cortes, Jorge ; Ravandi-Kashani, Farhad ; Giles, Francis ; Lerner, Susan ; Kantarjian, Happ ; Keating, Michael. / A retrospective comparison of three sequential groups of patients with recurrent/refractory chronic lymphocytic leukemia treated with fludarabine-based regimens. In: Cancer. 2006 ; Vol. 106, No. 2. pp. 337-345.
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abstract = "BACKGROUND. Combining therapeutics with single-agent activity has improved treatment for patients with many malignancies. Debate continues about the impact of treatment on survival in patients with chronic lymphocytic leukemia (CLL). Purine analogues are the most active agents for treatment of patients with CLL. Recently, it was shown that a chemoimmunotherapy regimen combining fludarabine (F), cyclophosphamide (C), and rituximab (R) (FCR) was very effective in treating patients with recurrent and/or refractory CLL. The objective of the current analysis was to determine whether improvements in treatment have had an impact on survival for patients with CLL. METHODS. Three nonoverlapping, sequential groups of patients enrolled on Phase II studies who received treatment with F (n = 251 patients), FC (n = 111 patients), or FCR (n = 143 patients) were analyzed. Pretreatment characteristics, responses to treatment, and overall survival were compared. RESULTS. Patients who were treated with FCR had a higher complete remission rate compared with patients who were treated with combined F and C or with F alone. Statistically significantly longer estimated median survival was noted for patients who received FCR. A Cox proportional hazards, multivariable model for overall survival that included all patients (n = 505) showed that patients who received FCR had longer survival (P < 0.0001) after adjusting for other significant (P < 0.05) pretreatment characteristics, including age, hemoglobin, β-2 microglobulin, and the number of prior treatments. CONCLUSIONS. The results of this retrospective comparison of patients with recurrent and refractory CLL indicated a higher complete remission rate and the longest estimated survival for patients who were treated with FCR, providing the basis for randomized clinical trials of this regimen.",
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T1 - A retrospective comparison of three sequential groups of patients with recurrent/refractory chronic lymphocytic leukemia treated with fludarabine-based regimens

AU - Wierda, William

AU - O'Brien, Susan

AU - Faderl, Stefan

AU - Ferrajoli, Alessandra

AU - Wang, Xuemei

AU - Do, Kim Anh

AU - Garcia-Manero, Guillermo

AU - Thomas, Deborah

AU - Cortes, Jorge

AU - Ravandi-Kashani, Farhad

AU - Giles, Francis

AU - Lerner, Susan

AU - Kantarjian, Happ

AU - Keating, Michael

PY - 2006/1/15

Y1 - 2006/1/15

N2 - BACKGROUND. Combining therapeutics with single-agent activity has improved treatment for patients with many malignancies. Debate continues about the impact of treatment on survival in patients with chronic lymphocytic leukemia (CLL). Purine analogues are the most active agents for treatment of patients with CLL. Recently, it was shown that a chemoimmunotherapy regimen combining fludarabine (F), cyclophosphamide (C), and rituximab (R) (FCR) was very effective in treating patients with recurrent and/or refractory CLL. The objective of the current analysis was to determine whether improvements in treatment have had an impact on survival for patients with CLL. METHODS. Three nonoverlapping, sequential groups of patients enrolled on Phase II studies who received treatment with F (n = 251 patients), FC (n = 111 patients), or FCR (n = 143 patients) were analyzed. Pretreatment characteristics, responses to treatment, and overall survival were compared. RESULTS. Patients who were treated with FCR had a higher complete remission rate compared with patients who were treated with combined F and C or with F alone. Statistically significantly longer estimated median survival was noted for patients who received FCR. A Cox proportional hazards, multivariable model for overall survival that included all patients (n = 505) showed that patients who received FCR had longer survival (P < 0.0001) after adjusting for other significant (P < 0.05) pretreatment characteristics, including age, hemoglobin, β-2 microglobulin, and the number of prior treatments. CONCLUSIONS. The results of this retrospective comparison of patients with recurrent and refractory CLL indicated a higher complete remission rate and the longest estimated survival for patients who were treated with FCR, providing the basis for randomized clinical trials of this regimen.

AB - BACKGROUND. Combining therapeutics with single-agent activity has improved treatment for patients with many malignancies. Debate continues about the impact of treatment on survival in patients with chronic lymphocytic leukemia (CLL). Purine analogues are the most active agents for treatment of patients with CLL. Recently, it was shown that a chemoimmunotherapy regimen combining fludarabine (F), cyclophosphamide (C), and rituximab (R) (FCR) was very effective in treating patients with recurrent and/or refractory CLL. The objective of the current analysis was to determine whether improvements in treatment have had an impact on survival for patients with CLL. METHODS. Three nonoverlapping, sequential groups of patients enrolled on Phase II studies who received treatment with F (n = 251 patients), FC (n = 111 patients), or FCR (n = 143 patients) were analyzed. Pretreatment characteristics, responses to treatment, and overall survival were compared. RESULTS. Patients who were treated with FCR had a higher complete remission rate compared with patients who were treated with combined F and C or with F alone. Statistically significantly longer estimated median survival was noted for patients who received FCR. A Cox proportional hazards, multivariable model for overall survival that included all patients (n = 505) showed that patients who received FCR had longer survival (P < 0.0001) after adjusting for other significant (P < 0.05) pretreatment characteristics, including age, hemoglobin, β-2 microglobulin, and the number of prior treatments. CONCLUSIONS. The results of this retrospective comparison of patients with recurrent and refractory CLL indicated a higher complete remission rate and the longest estimated survival for patients who were treated with FCR, providing the basis for randomized clinical trials of this regimen.

KW - Chronic lymphocytic leukemia

KW - Cyclophosphamide

KW - Fludarabine

KW - Rituximab

KW - Salvage

KW - Treatment

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