A phase II study of tipifarnib and gemcitabine in metastatic breast cancer
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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.
KeywordsMetastatic breast cancer Tipifarnib Gemcitabine Phase II trial
This work was supported in part by the National Institutes of Health/National Cancer Institute (N01-CM-2011-00039). Tipifarnib was provided by the National Cancer Institute (NCI) under a Clinical Trials Agreement (CTA) with Johnson & Johnson Pharmaceutical Research and Development LLC.
Compliance with ethical standards
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Conflict of interest
The authors declare no relevant potential conflicts of interest.
Informed consent was obtained from all individual participants included in the study.
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