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A phase II trial of capecitabine in combination with the farnesyltransferase inhibitor tipifarnib in patients with anthracycline-treated and taxane-resistant metastatic breast cancer: an Eastern Cooperative Oncology Group Study (E1103)

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Abstract

Capecitabine produces an objective response rate of up to 25 % in anthracycline-treated, taxane-resistant metastatic breast cancer (MBC). The farnesyltransferase inhibitor tipifarnib inhibits Ras signaling and has clinical activity when used alone in MBC. The objective of this study was to determine the efficacy and safety of tipifarnib–capecitabine combination in MBC patients who were previously treated with an anthracycline and progressed on taxane therapy. Eligible patients received oral capecitabine 1,000 mg/m2 twice daily plus oral tipifarnib 300 mg twice daily on days 1–14 every 21 days. The primary endpoint was ORR. The trial was powered to detect an improvement in response rate from 25 to 40 %. Among 63 eligible, partial response occurred in six patients (9.5 %; 90 % CI 4.2–17.9 %), median progression-free survival was 2.6 months (95 % CI 2.1–4.4), and median overall survival was 11.4 months (95 % CI 7.7–14.0). Dose modifications were required for 43 patients (68 %) for either tipifarnib and/or capecitabine. Grades 3 and 4 toxicities were seen in 30 patients (44 %; 90 % CI 44.4–67.0 %) and 11 patients (16 %; 90 % CI 10.8–29.0 %), respectively. The most common grade 3 toxicities included neutropenia, nausea, and vomiting; and the most common grade 4 toxicity was neutropenia (8 out of 11 cases). The tipifarnib–capecitabine combination is not more effective than capecitabine alone in MBC patients who were previously treated with an anthracycline and taxane therapy.

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Acknowledgments

This study was conducted by the ECOG (Robert L. Comis, MD, Chair) and supported in part by Public Health Service Grants CA23318 (to the EGOG statistical center), CA66636 (to the ECOG data management center), CA21115 (to the ECOG coordinating center), CA14958 (to Albert Einstein College of Medicine), CA17145 (to Northwestern University Medical Center), CA49883 (to Indiana University Medical Center), CA25224 (to NCCTG) and from the National Cancer Institute, National Institutes of Health and the Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Cancer Institute. TL is also supported by UL1 RR024146 from the National Center for Research Resources.

Conflict of interest

All authors disclose any financial and personal relationships with other people or organizations that could inappropriately influence their study.

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Author notes

  1. Tianhong Li

    Present address: Division of Hematology & Oncology, University of California Davis Cancer Center, 4501 X Street, Suite 3016, Sacramento, CA, 95817, USA

Authors and Affiliations

  1. Montefiore Medical Center, Albert Einstein Cancer Center, Bronx, NY, USA

    Tianhong Li & Joseph A. Sparano

  2. Dana-Farber Cancer, Boston, MA, USA

    Mengye Guo & Molin Wang

  3. Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA

    William J. Gradishar

  4. Mayo Clinic, Jacksonville, FL, USA

    Edith A. Perez

  5. Indiana University Cancer Center, Indianapolis, IN, USA

    George W. Sledge

Authors
  1. Tianhong Li
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  2. Mengye Guo
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  4. Joseph A. Sparano
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Correspondence to Tianhong Li.

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Li, T., Guo, M., Gradishar, W.J. et al. A phase II trial of capecitabine in combination with the farnesyltransferase inhibitor tipifarnib in patients with anthracycline-treated and taxane-resistant metastatic breast cancer: an Eastern Cooperative Oncology Group Study (E1103). Breast Cancer Res Treat 134, 345–352 (2012). https://doi.org/10.1007/s10549-012-2071-z

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  • DOI: https://doi.org/10.1007/s10549-012-2071-z

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