title: Paclitaxel, carboplatin, and trastuzumab in a neo-adjuvant regimen for HER2-positive breast cancer.
abstract: To evaluate a nonanthracycline-containing regimen consisting of 24 weekly administrations of paclitaxel, carboplatin, and trastuzumab as neo-adjuvant therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Patients with stage II or III breast cancer, including inflammatory disease, with HER2 overexpression (immunohistochemistry and/or fluorescent in situ hybridization) were treated with 24 weekly administrations of paclitaxel 70 mg/m(2) , carboplatin AUC = 3 mg/mL/minute, and trastuzumab 2 mg/kg (loading dose 4 mg/kg). In cycles 7, 8, 15, 16, 23, and 24, only trastuzumab was given. The primary end point was pathologic complete response (pCR) in both breast and axilla. Of 61 evaluable patients, 61% had stage II disease and 75% were node-positive. The median NRI (Neoadjuvant Response Index, a measure of the degree of downstaging by chemotherapy) of all patients was 0.86. Twenty-seven (44%) had a NRI of 1.0, which corresponds to pCR in breast and lymph nodes. The most commonly reported grade 3/4 toxicities were neutropenia (72%) and thrombocytopenia (36%). Dose reduction was necessary in 51% of the patients. A weekly carboplatin-paclitaxel-trastuzumab neo-adjuvant regimen is highly active in HER2-positive breast cancer with an acceptable toxicity profile. A multicenter phase 2 trial has recently reached its accrual target and will serve as a basis for a subsequent randomized phase 3 study comparing this regimen to a similar regimen preceded by anthracyclines.
authors.affiliation: Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands. g.sonke@nki.nl
authors.forename: Gabe S
authors.initials: GS
authors.lastname: Sonke
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Mandjes
authors.forename: Marjo J
authors.initials: MJ
authors.lastname: Holtkamp
authors.forename: Margaret
authors.initials: M
authors.lastname: Schot
authors.forename: Erik
authors.initials: E
authors.lastname: van Werkhoven
authors.forename: Jelle
authors.initials: J
authors.lastname: Wesseling
authors.forename: Marie-Jeanne
authors.initials: MJ
authors.lastname: Vrancken Peeters
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Rodenhuis
authors.forename: Sabine C
authors.initials: SC
authors.lastname: Linn
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012074:Remission Induction; D013921:Thrombocytopenia / Q000139:chemically induced; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D016190:Carboplatin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human
keywords: breast cancer; chemotherapy; neo-adjuvant; trastuzumab