Maximum Dose of Trastuzumab
The maximum single dose of trastuzumab is 8 mg/kg given intravenously as a loading dose, followed by maintenance doses of 6 mg/kg every 3 weeks. 1, 2
Standard Dosing Regimens
Trastuzumab can be administered using two evidence-based dosing schedules, both of which are recommended by the American Society of Clinical Oncology (ASCO) and the National Comprehensive Cancer Network (NCCN):
Every-3-Week Regimen (Higher Individual Doses)
- Loading dose: 8 mg/kg IV (this is the maximum single dose) 3, 1, 2
- Maintenance dose: 6 mg/kg IV every 3 weeks 3, 1, 2
- This regimen is continued for 1 year of total treatment 3
Weekly Regimen (Lower Individual Doses)
- Loading dose: 4 mg/kg IV 3, 1, 2
- Maintenance dose: 2 mg/kg IV weekly 3, 1, 2
- This regimen is also continued for 1 year of total treatment 3
Important Clinical Considerations
Both regimens achieve therapeutic serum concentrations, but the every-3-week schedule delivers the highest single dose at 8 mg/kg. The weekly regimen achieves steady-state trough concentrations of approximately 64.9 μg/mL, while the every-3-week regimen achieves approximately 47.3 μg/mL. 4
Subcutaneous Formulation
- A fixed dose of 600 mg subcutaneously every 3 weeks is an alternative that has demonstrated non-inferiority to intravenous administration 5
- This formulation actually achieves higher trough concentrations (69.0 μg/mL) compared to standard IV dosing 5
Cardiac Monitoring Requirements
Mandatory cardiac monitoring is required at baseline, 3,6, and 9 months due to cardiotoxicity risk, particularly when combined with anthracyclines. 3, 1 Cardiac events occur more frequently with longer treatment duration (5.7% at 12 months vs 1.9% at 6 months). 6
Duration of Therapy
The standard treatment duration is 1 year (52 weeks). 3, 6 A trial comparing 6 months versus 12 months failed to demonstrate non-inferiority of the shorter duration, confirming that 12 months remains the standard of care despite higher cardiac event rates. 6