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Tolerability of and adherence to combination oral therapy with gefitinib and capecitabine in metastatic breast cancer

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Abstract

Purpose: This phase I study explored gefitinib (G) and capecitabine (C) in metastatic breast cancer (MBC). Methods: Sequential cohorts (n = 3) received G and escalating C on a 14 day on/7 day off schedule, with a validation cohort (n = 10) at the maximum tolerated dose (MTD). Dose limiting toxicity (DLT) was defined in cycle 1. The primary endpoint was safety; secondary endpoints included response and adherence. Results: About 19 patients were treated for a median of 5 cycles. No patients in sequential cohorts experienced DLT; C MTD was 2,000 mg/m2/day when paired with daily G 250 mg. In the validation cohort, four experienced serious toxicities, including diarrhea, mucositis, and palmarplantar dysesthesia. At the MTD, 6 (46%) required a C dose reduction, and 3 (23%) came off study for toxicity. One partial response was observed (8%, 95% CI 0.2–38.5%); five had stable disease >24 weeks (26, 95% CI 9–51%). Patients missed few drug doses, with the suggestion of overadherence to therapy. Conclusions: In this phase I study of G and C in MBC, a C MTD was identified, and significant toxicity was observed. About 8% demonstrated a response, with 26% maintaining stable disease. The possibility of overadherence, as suggested in this study, may have implications for other trials of oral antineoplastic therapy.

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Acknowledgments

We thank AstraZeneca for providing gefitinib and support for the clinical trial.

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Authors and Affiliations

  1. Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Mayer 224, Boston, MA, 02115, USA

    E. L. Mayer

  2. Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, MA, 02115, USA

    A. H. Partridge, R. S. Gelman, H. J. Burstein & E. P. Winer

  3. Yale University, New Haven, CT, USA

    L. N. Harris

  4. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, 02215, USA

    S. T. Schumer

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  1. E. L. Mayer
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Correspondence to E. L. Mayer.

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Mayer, E.L., Partridge, A.H., Harris, L.N. et al. Tolerability of and adherence to combination oral therapy with gefitinib and capecitabine in metastatic breast cancer. Breast Cancer Res Treat 117, 615–623 (2009). https://doi.org/10.1007/s10549-009-0366-5

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