title: A phase Ib study of preoperative lapatinib, paclitaxel, and gemcitabine combination therapy in women with HER2 positive early breast cancer.
abstract: 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/m(2)) and gemcitabine (1,000 or 1,200 mg/m(2)) 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/m(2) 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.
authors: Center for Breast Cancer, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do, 410-769, Korea.
authors: In Hae
authors: IH
authors: Park
authors: Keun Seok
authors: KS
authors: Lee
authors: Han-Sung
authors: HS
authors: Kang
authors: Seok Won
authors: SW
authors: Kim
authors: Seeyoun
authors: S
authors: Lee
authors: So-Youn
authors: SY
authors: Jung
authors: Youngmee
authors: Y
authors: Kwon
authors: Kyung Hwan
authors: KH
authors: Shin
authors: Kyounglan
authors: K
authors: Ko
authors: Byung-Ho
authors: BH
authors: Nam
authors: Jungsil
authors: J
authors: Ro
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000601:surgery; D015331:Cohort Studies; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077341:Lapatinib; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D000077341:Lapatinib; D017239:Paclitaxel; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; D000093542:Gemcitabine