Doxorubicin is a cornerstone anthracycline chemotherapy drug widely used in oncology, known for its potent antitumor activity but also for its dose-limiting cardiotoxicity.
Pharmacological Class
- Anthracycline antibiotic (antineoplastic agent)
Mechanism of Action
- DNA intercalation → disrupts replication and transcription.
- Inhibits topoisomerase II → prevents DNA repair and replication.
- Generates free radicals → causes oxidative damage to DNA and cell membranes.
- Cell-cycle nonspecific, but most active in rapidly dividing cells.
Oncology Indications
- Breast cancer (e.g., part of AC regimen: doxorubicin + cyclophosphamide)
- Lymphomas (e.g., CHOP regimen)
- Leukemias
- Sarcomas (soft tissue, bone)
- Ovarian, bladder, and other solid tumors
Adult Dosing Examples (typical IV dosing)
- Single-agent: 60–75 mg/m² IV every 21 days
- Combination regimens: 40–60 mg/m² IV every 21 days
- Cumulative lifetime dose limit: ~450–550 mg/m² (lower if prior mediastinal radiation or other risk factors) to reduce risk of irreversible cardiomyopathy.
Pediatric Dosing
- 30 mg/m² IV on day 1, every 3 weeks, or protocol-specific dosing.
- Cumulative dose limit also applies.
Formulations
- Conventional doxorubicin hydrochloride (red solution; “red devil” nickname)
- Liposomal doxorubicin (e.g., Doxil®, Caelyx®) — altered PK, reduced cardiotoxicity, but more hand-foot syndrome.
Adverse Effects
Acute:
- Myelosuppression (dose-limiting)
- Nausea, vomiting (moderate emetogenic potential)
- Mucositis, alopecia
- Red-orange urine discoloration (harmless but notable for patient counseling)
Chronic:
- Cardiotoxicity (dilated cardiomyopathy, heart failure)
- Secondary malignancies (AML/MDS)
- Potent vesicant → can cause severe tissue necrosis; manage with dexrazoxane or cold packs.
Key Clinical Considerations for Oncology Pharmacists
- Cardiac monitoring: Baseline LVEF (echocardiogram or MUGA) before starting; repeat if cumulative dose increases or symptoms develop.
- Cumulative dose awareness: Track across lifetime and across regimens.
- Drug interactions: Avoid concurrent use with other cardiotoxic agents when possible (e.g., trastuzumab).
- Vesicant precautions: Central line preferred for administration.
- Dexrazoxane may be used:
- As a cardioprotective agent in metastatic breast cancer patients receiving high cumulative doses.
- For extravasation management.