Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment

Eva S. Thomas, Henry L. Gomez, Rubi K. Li, Hyun Cheol Chung, Luis E. Fein, Valorie F. Chan, Jacek Jassem, Xavier B. Pivot, Judith V. Klimovsky, Fernando Hurtado De Mendoza, Binghe Xu, Mario Campone, Guillermo L. Lerzo, Ronald A. Peck, Pralay Mukhopadhyay, Linda T. Vahdat, Henri H. Roché

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Abstract

Purpose: Effective treatment options for patients with metastatic breast cancer resistant to anthracyclines and taxanes are limited. Ixabepilone has single-agent activity in these patients and has demonstrated synergy with capecitabine in this setting. This study was designed to compare ixabepilone plus capecitabine versus capecitabine alone in anthracycline-pretreated or -resistant and taxane-resistant locally advanced or metastatic breast cancer. Patients and Methods: Seven hundred fifty-two patients were randomly assigned to ixabepilone 40 mg/m2 intravenously on day 1 of a 21-day cycle plus capecitabine 2,000 mg/m2 orally on days 1 through 14 of a 21-day cycle, or capecitabine alone 2,500 mg/m2 on the same schedule, in this international phase III study. The primary end point was progression-free survival evaluated by blinded independent review. Results: Ixabepilone plus capecitabine prolonged progression-free survival relative to capecitabine (median, 5.8 v 4.2 months), with a 25% reduction in the estimated risk of disease progression (hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P = .0003). Objective response rate was also increased (35% v 14%; P < .0001). Grade 3/4 treatment-related sensory neuropathy (21% v 0%), fatigue (9% v 3%), and neutropenia (68% v 11%) were more frequent with combination therapy, as was the rate of death as a result of toxicity (3% v 1%, with patients with liver dysfunction [≥ grade 2 liver function tests] at greater risk). Capecitabine-related toxicities were similar for both treatment groups. Conclusion: Ixabepilone plus capecitabine demonstrates superior efficacy to capecitabine alone in patients with metastatic breast cancer pretreated or resistant to anthracyclines and resistant to taxanes.

Original languageEnglish
Pages (from-to)5210-5217
Number of pages8
JournalJournal of Clinical Oncology
Volume25
Issue number33
DOIs
Publication statusPublished - 2007 Nov 20

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Anthracyclines
Breast Neoplasms
Therapeutics
Taxoids
Disease-Free Survival
Capecitabine
ixabepilone
taxane
Liver Function Tests
Neutropenia
Fatigue
Disease Progression
Liver Diseases
Appointments and Schedules
Mortality

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Thomas, Eva S. ; Gomez, Henry L. ; Li, Rubi K. ; Chung, Hyun Cheol ; Fein, Luis E. ; Chan, Valorie F. ; Jassem, Jacek ; Pivot, Xavier B. ; Klimovsky, Judith V. ; De Mendoza, Fernando Hurtado ; Xu, Binghe ; Campone, Mario ; Lerzo, Guillermo L. ; Peck, Ronald A. ; Mukhopadhyay, Pralay ; Vahdat, Linda T. ; Roché, Henri H. / Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. In: Journal of Clinical Oncology. 2007 ; Vol. 25, No. 33. pp. 5210-5217.
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title = "Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment",
abstract = "Purpose: Effective treatment options for patients with metastatic breast cancer resistant to anthracyclines and taxanes are limited. Ixabepilone has single-agent activity in these patients and has demonstrated synergy with capecitabine in this setting. This study was designed to compare ixabepilone plus capecitabine versus capecitabine alone in anthracycline-pretreated or -resistant and taxane-resistant locally advanced or metastatic breast cancer. Patients and Methods: Seven hundred fifty-two patients were randomly assigned to ixabepilone 40 mg/m2 intravenously on day 1 of a 21-day cycle plus capecitabine 2,000 mg/m2 orally on days 1 through 14 of a 21-day cycle, or capecitabine alone 2,500 mg/m2 on the same schedule, in this international phase III study. The primary end point was progression-free survival evaluated by blinded independent review. Results: Ixabepilone plus capecitabine prolonged progression-free survival relative to capecitabine (median, 5.8 v 4.2 months), with a 25{\%} reduction in the estimated risk of disease progression (hazard ratio, 0.75; 95{\%} CI, 0.64 to 0.88; P = .0003). Objective response rate was also increased (35{\%} v 14{\%}; P < .0001). Grade 3/4 treatment-related sensory neuropathy (21{\%} v 0{\%}), fatigue (9{\%} v 3{\%}), and neutropenia (68{\%} v 11{\%}) were more frequent with combination therapy, as was the rate of death as a result of toxicity (3{\%} v 1{\%}, with patients with liver dysfunction [≥ grade 2 liver function tests] at greater risk). Capecitabine-related toxicities were similar for both treatment groups. Conclusion: Ixabepilone plus capecitabine demonstrates superior efficacy to capecitabine alone in patients with metastatic breast cancer pretreated or resistant to anthracyclines and resistant to taxanes.",
author = "Thomas, {Eva S.} and Gomez, {Henry L.} and Li, {Rubi K.} and Chung, {Hyun Cheol} and Fein, {Luis E.} and Chan, {Valorie F.} and Jacek Jassem and Pivot, {Xavier B.} and Klimovsky, {Judith V.} and {De Mendoza}, {Fernando Hurtado} and Binghe Xu and Mario Campone and Lerzo, {Guillermo L.} and Peck, {Ronald A.} and Pralay Mukhopadhyay and Vahdat, {Linda T.} and Roch{\'e}, {Henri H.}",
year = "2007",
month = "11",
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Thomas, ES, Gomez, HL, Li, RK, Chung, HC, Fein, LE, Chan, VF, Jassem, J, Pivot, XB, Klimovsky, JV, De Mendoza, FH, Xu, B, Campone, M, Lerzo, GL, Peck, RA, Mukhopadhyay, P, Vahdat, LT & Roché, HH 2007, 'Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment', Journal of Clinical Oncology, vol. 25, no. 33, pp. 5210-5217. https://doi.org/10.1200/JCO.2007.12.6557

Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. / Thomas, Eva S.; Gomez, Henry L.; Li, Rubi K.; Chung, Hyun Cheol; Fein, Luis E.; Chan, Valorie F.; Jassem, Jacek; Pivot, Xavier B.; Klimovsky, Judith V.; De Mendoza, Fernando Hurtado; Xu, Binghe; Campone, Mario; Lerzo, Guillermo L.; Peck, Ronald A.; Mukhopadhyay, Pralay; Vahdat, Linda T.; Roché, Henri H.

In: Journal of Clinical Oncology, Vol. 25, No. 33, 20.11.2007, p. 5210-5217.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment

AU - Thomas, Eva S.

AU - Gomez, Henry L.

AU - Li, Rubi K.

AU - Chung, Hyun Cheol

AU - Fein, Luis E.

AU - Chan, Valorie F.

AU - Jassem, Jacek

AU - Pivot, Xavier B.

AU - Klimovsky, Judith V.

AU - De Mendoza, Fernando Hurtado

AU - Xu, Binghe

AU - Campone, Mario

AU - Lerzo, Guillermo L.

AU - Peck, Ronald A.

AU - Mukhopadhyay, Pralay

AU - Vahdat, Linda T.

AU - Roché, Henri H.

PY - 2007/11/20

Y1 - 2007/11/20

N2 - Purpose: Effective treatment options for patients with metastatic breast cancer resistant to anthracyclines and taxanes are limited. Ixabepilone has single-agent activity in these patients and has demonstrated synergy with capecitabine in this setting. This study was designed to compare ixabepilone plus capecitabine versus capecitabine alone in anthracycline-pretreated or -resistant and taxane-resistant locally advanced or metastatic breast cancer. Patients and Methods: Seven hundred fifty-two patients were randomly assigned to ixabepilone 40 mg/m2 intravenously on day 1 of a 21-day cycle plus capecitabine 2,000 mg/m2 orally on days 1 through 14 of a 21-day cycle, or capecitabine alone 2,500 mg/m2 on the same schedule, in this international phase III study. The primary end point was progression-free survival evaluated by blinded independent review. Results: Ixabepilone plus capecitabine prolonged progression-free survival relative to capecitabine (median, 5.8 v 4.2 months), with a 25% reduction in the estimated risk of disease progression (hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P = .0003). Objective response rate was also increased (35% v 14%; P < .0001). Grade 3/4 treatment-related sensory neuropathy (21% v 0%), fatigue (9% v 3%), and neutropenia (68% v 11%) were more frequent with combination therapy, as was the rate of death as a result of toxicity (3% v 1%, with patients with liver dysfunction [≥ grade 2 liver function tests] at greater risk). Capecitabine-related toxicities were similar for both treatment groups. Conclusion: Ixabepilone plus capecitabine demonstrates superior efficacy to capecitabine alone in patients with metastatic breast cancer pretreated or resistant to anthracyclines and resistant to taxanes.

AB - Purpose: Effective treatment options for patients with metastatic breast cancer resistant to anthracyclines and taxanes are limited. Ixabepilone has single-agent activity in these patients and has demonstrated synergy with capecitabine in this setting. This study was designed to compare ixabepilone plus capecitabine versus capecitabine alone in anthracycline-pretreated or -resistant and taxane-resistant locally advanced or metastatic breast cancer. Patients and Methods: Seven hundred fifty-two patients were randomly assigned to ixabepilone 40 mg/m2 intravenously on day 1 of a 21-day cycle plus capecitabine 2,000 mg/m2 orally on days 1 through 14 of a 21-day cycle, or capecitabine alone 2,500 mg/m2 on the same schedule, in this international phase III study. The primary end point was progression-free survival evaluated by blinded independent review. Results: Ixabepilone plus capecitabine prolonged progression-free survival relative to capecitabine (median, 5.8 v 4.2 months), with a 25% reduction in the estimated risk of disease progression (hazard ratio, 0.75; 95% CI, 0.64 to 0.88; P = .0003). Objective response rate was also increased (35% v 14%; P < .0001). Grade 3/4 treatment-related sensory neuropathy (21% v 0%), fatigue (9% v 3%), and neutropenia (68% v 11%) were more frequent with combination therapy, as was the rate of death as a result of toxicity (3% v 1%, with patients with liver dysfunction [≥ grade 2 liver function tests] at greater risk). Capecitabine-related toxicities were similar for both treatment groups. Conclusion: Ixabepilone plus capecitabine demonstrates superior efficacy to capecitabine alone in patients with metastatic breast cancer pretreated or resistant to anthracyclines and resistant to taxanes.

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