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)

Tianhong Li; Mengye Guo; William J. Gradishar; Joseph A. Sparano; Edith A. Perez; Molin Wang; George W. Sledge

doi:10.1007/s10549-012-2071-z

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)

Tianhong Li^*, Mengye Guo, William J. Gradishar, Joseph A. Sparano, Edith A. Perez, Molin Wang, George W. Sledge

^*Corresponding author for this work

Medicine, Hematology Oncology Division

Research output: Contribution to journal › Article › peer-review

19 Scopus citations

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.

Original language	English (US)
Pages (from-to)	345-352
Number of pages	8
Journal	Breast Cancer Research and Treatment
Volume	134
Issue number	1
DOIs	https://doi.org/10.1007/s10549-012-2071-z
State	Published - Jul 2012

Funding

The study was coordinated and conducted by the ECOG, and the North Central Cancer Treatment Group (NCCTG) also participated. The trial was reviewed, approved, and sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute (ClinicalTrials.gov, identifier NCT00077363, E1103). The local institutional review board at each participating institution approved the protocol. All patients gave written, informed consent. 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.

Keywords

Capecitabine
Farnesyltransferase inhibitor
Metastatic breast cancer
Tipifarnib

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Li, T., Guo, M., Gradishar, W. J., Sparano, J. A., Perez, E. A., Wang, M., & Sledge, G. W. (2012). 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 Research and Treatment, 134(1), 345-352. https://doi.org/10.1007/s10549-012-2071-z

Li, Tianhong ; Guo, Mengye ; Gradishar, William 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). In: Breast Cancer Research and Treatment. 2012 ; Vol. 134, No. 1. pp. 345-352.

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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.",

keywords = "Capecitabine, Farnesyltransferase inhibitor, Metastatic breast cancer, Tipifarnib",

author = "Tianhong Li and Mengye Guo and Gradishar, {William J.} and Sparano, {Joseph A.} and Perez, {Edith A.} and Molin Wang and Sledge, {George W.}",

note = "Funding Information: The study was coordinated and conducted by the ECOG, and the North Central Cancer Treatment Group (NCCTG) also participated. The trial was reviewed, approved, and sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute (ClinicalTrials.gov, identifier NCT00077363, E1103). The local institutional review board at each participating institution approved the protocol. All patients gave written, informed consent. Funding Information: 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.",

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Li, T, Guo, M, Gradishar, WJ, Sparano, JA, Perez, EA, Wang, M & Sledge, GW 2012, '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 Research and Treatment, vol. 134, no. 1, pp. 345-352. https://doi.org/10.1007/s10549-012-2071-z

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). / Li, Tianhong; Guo, Mengye; Gradishar, William J. et al.
In: Breast Cancer Research and Treatment, Vol. 134, No. 1, 07.2012, p. 345-352.

Research output: Contribution to journal › Article › peer-review

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AB - 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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Li T, Guo M, Gradishar WJ, Sparano JA, Perez EA, Wang M 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 Research and Treatment. 2012 Jul;134(1):345-352. doi: 10.1007/s10549-012-2071-z

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)

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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