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Phase I Trial of Uracil–Ftorafur, Leucovorin, and Etoposide: An Active All-oral Regimen for Metastatic Breast Cancer

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Abstract

Purpose. To determine the maximum tolerated doses, toxicities, and therapeutic effect of an oral chemotherapy regimen consisting of uracil–ftorafur, etoposide, and leucovorin for metastatic breast cancer.

Patients and methods. The regimen consists of 28-day cycles of uracil–ftorafur, etoposide, and leucovorin administered orally on days 1–14. The dose of etoposide was fixed at 50 mg/m2/day, and uracil–ftorafur was escalated in 50 mg/m2/day increments from 200 to 350 mg/m2. Leucovorin, was used at a dose of 90 mg/day. Eligibility criteria required prior treatment with a taxane or anthracycline.

Results. A total of 23 patients were enrolled. Twenty patients are assessable for toxicity and 16 patients are assessable for response. All non-hematologic toxicities were grade 1 or 2. Three hematologic dose-limiting toxicities (DLTs) were observed. Partial responses were seen in 6 of 16 (37.5%, 95% confidence interval 15%, 85%) of assessable patients with durations ranging from 4 to 20 months. Stable disease was observed in 4 of 16 (25%) of patients with durations from 4 to 12 months. Median time to progression was 10.5 months. An intent to treat analysis revealed a response of 26%.

Conclusion. The recommended dose and schedule of this combination is uracil–ftorafur 350 mg/m2, leucovorin 90 mg/day, and etoposide 50 mg/m2 for two consecutive weeks in a 4-week cycle. This all-oral regimen is well tolerated and demonstrates encouraging efficacy in a cohort of heavily pretreated patient with metastatic breast cancer.

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Authors and Affiliations

  1. Division of Oncology, Stanford University School of Medicine, Stanford, CA, USA

    Anne-Renee Hartman, Amy Grekowicz, Bert L. Lum, Robert W. Carlson, Christine Schurman, Branimir I. Sikic, Richard Shapiro & Frank E. Stockdale

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  1. Anne-Renee Hartman
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  2. Amy Grekowicz
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  3. Bert L. Lum
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  4. Robert W. Carlson
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Hartman, AR., Grekowicz, A., Lum, B.L. et al. Phase I Trial of Uracil–Ftorafur, Leucovorin, and Etoposide: An Active All-oral Regimen for Metastatic Breast Cancer. Breast Cancer Res Treat 82, 61–69 (2003). https://doi.org/10.1023/B:BREA.0000003920.27391.ac

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