A phase Ib study of preoperative lapatinib, paclitaxel, and gemcitabine combination therapy in women with HER2 positive early breast cancer

초록

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/m 2 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. © 2011 Springer Science+Business Media, LLC.

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