What is the typical dose of doxorubicin (anthracycline antibiotic) for a patient with breast cancer?

Doxorubicin Dosing for Breast Cancer

For adjuvant treatment of early breast cancer, doxorubicin is dosed at 60 mg/m² IV every 3 weeks for 4 cycles when used in the AC (doxorubicin-cyclophosphamide) regimen, or 50 mg/m² IV every 3 weeks for 6 cycles when used in the TAC (docetaxel-doxorubicin-cyclophosphamide) regimen. 1

Adjuvant Setting (Early Breast Cancer)

Standard AC Regimen

• Doxorubicin 60 mg/m² IV on day 1 + cyclophosphamide 600 mg/m² IV on day 1, repeated every 21 days for 4 cycles 1, 2
• This is typically followed by sequential taxane therapy (paclitaxel 80 mg/m² weekly for 12 weeks or paclitaxel 175 mg/m² every 3 weeks for 4 cycles) 1
• The AC-followed-by-taxane approach is a Category 1 (highest level) NCCN recommendation for high-risk disease 1, 3

Dose-Dense AC Regimen

• Doxorubicin 60 mg/m² IV + cyclophosphamide 600 mg/m² IV every 14 days (not 21 days) for 4 cycles with mandatory G-CSF support 1
• Followed by paclitaxel 175 mg/m² every 14 days for 4 cycles 1
• This dose-dense schedule provides superior outcomes compared to standard 3-week intervals 3

TAC Regimen

• Doxorubicin 50 mg/m² IV + docetaxel 75 mg/m² IV + cyclophosphamide 500 mg/m² IV every 21 days for 6 cycles 1, 3
• Requires mandatory G-CSF support with all cycles 1, 3
• This is a preferred NCCN regimen but uses a lower doxorubicin dose per cycle 1

Metastatic Setting

Single-Agent Doxorubicin

• 60-75 mg/m² IV every 3 weeks produces objective response rates of 30-47% 1
• Alternative: 20 mg/m² IV weekly for patients requiring dose attenuation 1
• NCCN classifies single-agent doxorubicin as a "preferred" chemotherapy option for metastatic disease 1

Liposomal Doxorubicin

• 50 mg/m² IV every 4 weeks (note the longer interval compared to conventional doxorubicin) 1
• Produces equivalent efficacy to conventional doxorubicin 60 mg/m² every 3 weeks but with significantly reduced cardiotoxicity (7% vs 26%, HR 3.16) 1
• Trade-off: higher rates of palmar-plantar erythrodysesthesia (48% vs 2%) and mucositis (23% vs 13%) 1

Critical Cumulative Dose Limits

Maximum Lifetime Doses

• The recommended maximum cumulative dose is 400-550 mg/m² for conventional doxorubicin 1
• Risk of heart failure increases exponentially: 5% at 400 mg/m², 26% at 550 mg/m², and 48% at 700 mg/m² 1
• For two-drug regimens (like AC), cumulative doxorubicin should not exceed 240 mg/m² 1, 3
• For three-drug regimens, cumulative doxorubicin should be ≥240 mg/m² but not exceed 550 mg/m² 1

High-Risk Thresholds Requiring Cardioprotection

• Cumulative doxorubicin ≥250 mg/m² or epirubicin ≥600 mg/m² warrants cardioprotective strategies 1, 2
• At ≥250 mg/m², there is a 4.5-fold increased risk of heart failure compared to no anthracycline exposure 1
• Cardiac dysfunction risk is 9% at 250 mg/m², 18% at 350 mg/m², and 38% at 450 mg/m² 1

Cardiac Monitoring Requirements

Baseline and During Treatment

• Obtain baseline echocardiogram with LVEF assessment before initiating doxorubicin 2
• Mandatory cardiac monitoring after cumulative doxorubicin 240 mg/m² in high-risk patients 2
• Reassess cardiac function at 3,6, and 9 months when using trastuzumab-containing regimens 1

Criteria to Stop Treatment

• Discontinue if LVEF decreases by ≥10 percentage points to a value <50%, confirmed on repeat assessment after 3 weeks 2
• Stop immediately if clinical heart failure develops 2
• Never give trastuzumab concurrently with anthracyclines due to severe cardiotoxicity risk 1

Cardioprotective Strategies for High Cumulative Doses

When planning cumulative doxorubicin ≥250 mg/m²:

• Consider dexrazoxane as a cardioprotectant 2
• Use continuous infusion rather than bolus administration 2
• Switch to liposomal doxorubicin formulations (50 mg/m² every 4 weeks) 1, 2

Long-Term Surveillance

• Assess LVEF at 6 months post-treatment, then annually for 2-3 years, then every 3-5 years for life 1
• High-risk patients (those receiving >300 mg/m² or with underlying cardiovascular disease) require more frequent monitoring 1
• Any cardiovascular event during follow-up mandates more stringent surveillance 1

Common Pitfalls to Avoid

• Do not use weekly doxorubicin schedules in the adjuvant setting—the evidence base supports every-3-week dosing at 60 mg/m² 1
• Do not exceed 240 mg/m² cumulative dose in AC regimens (4 cycles × 60 mg/m² = 240 mg/m²) 1, 3
• Never co-administer anthracyclines with trastuzumab except in specific neoadjuvant protocols 1
• Do not use TAC regimen without G-CSF support—febrile neutropenia risk is unacceptably high 1, 3
• Patients who received adjuvant anthracyclines can be retreated with anthracycline-based regimens for metastatic disease if relapse occurred >12 months after completion, respecting cumulative dose limits 2