Originally published as JCO Early Release 10.1200/JCO.2006.09.3849 on July 2 2007
Journal of Clinical Oncology, Vol 25, No 23 (August 10), 2007: pp. 3407-3414
© 2007 American Society of Clinical Oncology.
Efficacy and Safety of Ixabepilone (BMS-247550) in a Phase II Study of Patients With Advanced Breast Cancer Resistant to an Anthracycline, a Taxane, and Capecitabine
Edith A. Perez,
Guillermo Lerzo,
Xavier Pivot,
Eva Thomas,
Linda Vahdat,
Linda Bosserman,
Patrice Viens,
Can Cai,
Brian Mullaney,
Ronald Peck,
Gabriel N. Hortobagyi
From the Department of Hematology and Oncology, Mayo Clinic, Jacksonville, FL; Division of Oncology, Hospital de Oncologia Maria Curie, Ciudad de Buenos Aires, Argentina; Division of Oncology, Centre Hospitalier Universitaire de Besançon, Besançon, France; Departments of Medicine and Breast Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX; Department of Medicine, Weill Cornell Breast Center, New York, NY; Department of Medical Oncology and Hematology, Wilshire Oncology Medical Group Inc, La Verne, CA; Department of Medical Oncology, Institut Paoli-Calmettes, Marseille, France; and Oncology Research, Bristol-Myers Squibb, Wallingford, CT
Address reprint requests to Edith A. Perez, MD, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, FL 32224; e-mail: Perez.edith{at}mayo.edu
Purpose: To evaluate the efficacy and safety of ixabepilone in patients with metastatic breast cancer (MBC) resistant to anthracycline, taxane, and capecitabine, in this multicenter, phase II study.
Patients and Methods: Patients with measurable disease who had tumor progression while receiving prior anthracycline, taxane, and capecitabine were enrolled. Ixabepilone 40 mg/m2 monotherapy was administered as a 3-hour intravenous infusion on day 1 of a 21-day cycle. The primary end point was objective response rate (ORR), assessed by an independent radiology facility (IRF).
Results: A total of 126 patients were treated and 113 were assessable for response. Patients were heavily pretreated: 88% had received at least two lines of prior chemotherapy in the metastatic setting. IRF-assessed ORR was 11.5% (95% CI, 6.3% to 18.9%) for response-assessable patients. Investigator-assessed ORR for all treated patients was 18.3% (95% CI, 11.9% to 26.1%). Fifty percent of patients achieved stable disease (SD); 14.3% achieved SD 6 months. Median duration of response and progression-free survival were 5.7 and 3.1 months, respectively. Median overall survival was 8.6 months. Patients received a median of 4.0 treatment cycles (range, one to 16 cycles), and 25% of patients received eight cycles. Grade 3/4 treatment-related events included peripheral sensory neuropathy (14%), fatigue/asthenia (13%), myalgia (8%), and stomatitis/mucositis (6%). Resolution of grade 3/4 peripheral sensory neuropathy occurred after a median period of 5.4 weeks.
Conclusion: Ixabepilone demonstrated clear activity and a manageable safety profile in patients with MBC resistant to anthracycline, taxane, and capecitabine. Responses were durable and notable in patients who had not previously responded to multiple prior therapies.
published online ahead of print at www.jco.org on July 2, 2007.
Supported by Bristol-Myers Squibb Co (study and editorial).
Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Related Editorial
- Ixabepilone and the Narrow Path to Developing New Cytotoxic Drugs
Luca Gianni
JCO 2007 25: 3389-3391
[Full Text]
This article has been cited by other articles:

|
 |

|
 |
 
X. Pivot, P. Koralewski, J. L. Hidalgo, A. Chan, A. Goncalves, G. Schwartsmann, S. Assadourian, and J. P. Lotz
A multicenter phase II study of XRP6258 administered as a 1-h i.v. infusion every 3 weeks in taxane-resistant metastatic breast cancer patients
Ann. Onc.,
September 1, 2008;
19(9):
1547 - 1552.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Bhushan and C. M Walko
Ixabepilone: A New Antimitotic for the Treatment of Metastatic Breast Cancer
Ann. Pharmacother.,
September 1, 2008;
42(9):
1252 - 1261.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. E. Dodd, E. L. Korn, B. Freidlin, C. C. Jaffe, L. V. Rubinstein, J. Dancey, and M. M. Mooney
Blinded Independent Central Review of Progression-Free Survival in Phase III Clinical Trials: Important Design Element or Unnecessary Expense?
J. Clin. Oncol.,
August 1, 2008;
26(22):
3791 - 3796.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Goel, G. L. Goldberg, D. Y.-S. Kuo, F. Muggia, J. Arezzo, and S. Mani
Novel neurosensory testing in cancer patients treated with the epothilone B analog, ixabepilone
Ann. Onc.,
July 21, 2008;
(2008)
mdn420v1.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Goodin
Novel cytotoxic agents: Epothilones
Am. J. Health Syst. Pharm.,
May 15, 2008;
65(10_Supplement_3):
S10 - S15.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Y. Barbour
Caring for the treatment-experienced breast cancer patient: The pharmacist's role
Am. J. Health Syst. Pharm.,
May 15, 2008;
65(10_Supplement_3):
S16 - S22.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. J. Lee and S. M. Swain
The Epothilones: Translating from the Laboratory to the Clinic
Clin. Cancer Res.,
March 15, 2008;
14(6):
1618 - 1624.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Vahdat
Ixabepilone: A Novel Antineoplastic Agent with Low Susceptibility to Multiple Tumor Resistance Mechanisms
Oncologist,
March 1, 2008;
13(3):
214 - 221.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. J. Wasserman and A. R. Tan
Evolving Strategies for the Treatment of "Triple-Negative" Breast Cancer
ASCO Educational Book,
January 1, 2008;
2008(1):
120 - 126.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. S. Thomas, H. L. Gomez, R. K. Li, H.-C. Chung, L. E. Fein, V. F. Chan, J. Jassem, X. B. Pivot, J. V. Klimovsky, F. H. de Mendoza, et al.
Ixabepilone Plus Capecitabine for Metastatic Breast Cancer Progressing After Anthracycline and Taxane Treatment
J. Clin. Oncol.,
November 20, 2007;
25(33):
5210 - 5217.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
The Epothilones Are Coming!
Journal Watch Oncology and Hematology,
August 28, 2007;
2007(828):
1 - 1.
[Full Text]
|
 |
|
|