The development, pharmacology, safety, efficacy, and dosage and administration 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
monoclonal 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 metastatic
breast cancer (MBC), response rates have ranged from 12% to 23% for single-agent
trastuzumab and from 25% to 62% for
trastuzumab plus
chemotherapy.
Trastuzumab increased time to
disease progression and survival time when administered in combination with
chemotherapy. The National Comprehensive
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.
Trastuzumab is administered weekly, with an initial i.v. dose of 4 mg/kg followed by weekly doses of 2 mg/kg. Most clinical trials continued treatment until
disease progression occurred. Adverse effects include infusion-related reactions manifested by
fever and
chills, exacerbation of
chemotherapy-induced gastrointestinal 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.