Paclitaxel, carboplatin, and trastuzumab in a neo-adjuvant regimen for HER2-positive breast cancer.
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.
['Sonke|Gabe S|GS|', 'Mandjes|Ingrid A|IA|', 'Holtkamp|Marjo J|MJ|', 'Schot|Margaret|M|', 'van Werkhoven|Erik|E|', 'Wesseling|Jelle|J|', 'Vrancken Peeters|Marie-Jeanne|MJ|', 'Rodenhuis|Sjoerd|S|', 'Linn|Sabine C|SC|']
D000328:Adult D000368:Aged D061067:Antibodies, Monoclonal, Humanized D000971:Antineoplastic Combined Chemotherapy Protocols D001943:Breast Neoplasms D016190:Carboplatin D005260:Female D006801:Humans D008875:Middle Aged D020360:Neoadjuvant Therapy D009503:Neutropenia D017239:Paclitaxel D018719:Receptor, ErbB-2 D012074:Remission Induction D013921:Thrombocytopenia D000068878:Trastuzumab D016896:Treatment Outcome
trastuzumab neo-adjuvant breast cancer chemotherapy