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01-04-2018 | PHASE II STUDIES

A phase II study of tipifarnib and gemcitabine in metastatic breast cancer

Authors: Clinton Yam, Rashmi K. Murthy, Vicente Valero, Janio Szklaruk, Girish S. Shroff, Carol J. Stalzer, Aman U. Buzdar, James L. Murray, Wei Yang, Gabriel N. Hortobagyi, Stacy L. Moulder, Banu Arun

Published in: Investigational New Drugs | Issue 2/2018

Summary

Background Tipifarnib is an orally active, competitive inhibitor of farnesyltransferase which has shown encouraging signs of activity either alone or when combined with other agents. Clinical studies of tipifarnib in combination with anti-estrogen therapy have yielded disappointing results. In contrast, tipifarnib appears to be synergistic in combination with anthracycline based chemotherapy. Here we report the results of the first prospective phase II trial evaluating the efficacy of the novel combination of tipifarnib and gemcitabine in the treatment of metastatic breast cancer. Patients and Methods 30 postmenopausal women with metastatic breast cancer were treated on a 21-day cycle with tipifarnib 300 mg PO twice daily from days 1 through 14. Gemcitabine was administered intravenously at a dose of 1000 mg/m² on days 1 and 8. Patients were treated until disease progression or unacceptable toxicity. Results There was one complete response and four partial responses yielding an objective response rate of 16.7%. Median progression-free survival and overall survival was 2.5 months (95% confidence interval: 1.6–5.7 months) and 13.1 months (95% confidence interval: 9.1–20.6 months), respectively. 40% of patients experienced grade 4 neutropenia in this study. Conclusion The combination of tipifarnib and gemcitabine is not well tolerated with high rates of myelosuppression and is not more effective than gemcitabine monotherapy in the treatment of metastatic breast cancer.

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Title: A phase II study of tipifarnib and gemcitabine in metastatic breast cancer
Authors: Clinton Yam
Rashmi K. Murthy
Vicente Valero
Janio Szklaruk
Girish S. Shroff
Carol J. Stalzer
Aman U. Buzdar
James L. Murray
Wei Yang
Gabriel N. Hortobagyi
Stacy L. Moulder
Banu Arun
Publication date: 01-04-2018
Publisher: Springer US
Published in: Investigational New Drugs / Issue 2/2018
Print ISSN: 0167-6997
Electronic ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-018-0564-2

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