Pharmacology and therapeutic use of trastuzumab in breast cancer

The development, pharmacology, safety, efficacy, and dosage and administrat ion of trastuzumab are reviewed. The discovery of HER2 gene amplification in up to 30% of women with breast cancer led to the development of trastuzumab, a humanized recombinant monoc lonal antibody directed against the HER2-receptor protein on breast cancer cells. In large, multicenter trials of trastuzumab as a single agent or in combination with chemotherapy as first-line or second-line therapy for meta static breast cancer (MBC), response rates have ranged from 12% to 23% for single-agent trastuzumab and from 25% to 62% for trastuzumab plus chemother apy. Trastuzumab increased time to disease progression and survival time wh en administered in combination with chemotherapy. The National Comprehensiv e Cancer Network guidelines for the treatment of breast cancer now include Trastuzumab and paclitaxel as an option for patients with MBC or recurrent breast cancer in which the HER2-receptor protein is overexpressed. Trastuzu mab is administered weekly, with an initial i.v, dose of 4 mg/kg followed b y weekly doses of 2 mg/kg. Most clinical trials continued treatment until d isease progression occurred. Adverse effects include infusion-related react ions manifested by fever and chills, exacerbation of chemotherapy-induced g astrointestinal toxicity and myelosuppression, and cardiotoxicity. Trastuzumab, either as a single agent or in combination with chemotherapy, can be an effective therapeutic option for MBC patients who overexpress the HER2-receptor protein and has changed the standard of care.