Summary
We conducted a phase I trial to determine the feasible dose for lapatinib, a dual HER2/EGFR tyrosine kinase inhibitor, with paclitaxel and gemcitabine as a neoadjuvant treatment in HER2 positive patients. In this phase I dose-escalation study, cohorts of 3–6 HER2-positive operable breast cancer patients received lapatinib (1,000 mg/day or 1,250 mg/day PO) with paclitaxel (80 mg/m2) and gemcitabine (1,000 or 1,200 mg/m2) on days 1 and 8 every 21 days to determine the tolerable dosages. Among 13 patients enrolled, 12 (stage III; n = 11: stage II; n = 1) completed treatment and one withdrew consent. The recommended doses were 1000-mg/day lapatinib, 80-mg/m2 paclitaxel, and 1,000-mg/m2 gemcitabine. One patient developed dose-limiting grade 3 hepatotoxicity; 3 experienced dose-limiting grade 4 neutropenia. No notable decline in left ventricle ejection fraction occurred. Eight patients achieved clinical partial response and four achieved clinical complete response (CR). Three patients (25%) achieved both tumor and nodal pathologic CR, 5 (42%) achieved tumor pathologic CR, and 6 (50%) underwent breast-conserving surgery. No relationship between lapatinib dose intensity and tumor response was apparent. Median follow-up was 16.2 (range, 6.5–20.7) months. Lapatinib plus paclitaxel and gemcitabine was tolerable with no overlapping toxicity.
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Acknowledgements
We are grateful to the National Cancer Center for supporting this study under grant number 0910320. We would also like to acknowledge all participating patients, research coordinators, and the GSK for providing lapatinib.
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The authors declared that they have no conflicting interests.
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Park, I.H., Lee, K.S., Kang, HS. et al. A phase Ib study of preoperative lapatinib, paclitaxel, and gemcitabine combination therapy in women with HER2 positive early breast cancer. Invest New Drugs 30, 1972–1977 (2012). https://doi.org/10.1007/s10637-011-9759-5
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DOI: https://doi.org/10.1007/s10637-011-9759-5