Definition:
Antitumor chemotherapeutics (chemotherapy) are drugs used to treat cancer by targeting rapidly dividing cells, interfering with DNA/RNA synthesis, mitosis, or cell metabolism.
Classification
- Antimetabolites:
- Azacitidine
- Fludarabine
- 5-Fluorouracil (5-FU)
- Methotrexate
- Antitumor Antibiotics:
- Bleomycin
- Doxorubicin
- Epirubicin
- Mitoxantrone
- Alkylating Agents:
- Busulfan
- Dacarbazine
- Lomustine
- Melphalan
- Microtubule Inhibitors:
- Docetaxel
- Vincristine
- Vinorelbine
Pharmacodynamics
- Antimetabolites: Mimic purines/pyrimidines → disrupt DNA/RNA synthesis in S phase → faulty replication → apoptosis
- Antitumor Antibiotics: Intercalate into DNA → inhibit topoisomerase II → block replication/transcription → DNA breaks
- Alkylating Agents: Alkylate DNA → form cross-links → DNA strand breakage → inhibit replication/transcription → cell death
- Microtubule Inhibitors:
- Taxanes (e.g., Docetaxel): Stabilize microtubules → block depolymerization
- Vinca alkaloids (e.g., Vincristine): Inhibit microtubule assembly ⤷ Both arrest cells in metaphase → mitotic arrest → apoptosis
Side Effects
- Common:
- Nausea, vomiting
- Hair loss (alopecia)
- Fatigue
- Myelosuppression → anemia, infections, bleeding
- Rare/Severe:
- Cardiotoxicity (e.g., doxorubicin)
- Nephrotoxicity, hepatotoxicity
- Neurotoxicity (e.g., vincristine → peripheral neuropathy)
- Secondary malignancies
- Severe hypersensitivity reactions
Drug Interactions
- ↑ bleeding risk with warfarin
- CYP450 inducers (e.g., phenytoin) ↓ drug efficacy
- CYP450 inhibitors (e.g., erythromycin) ↑ drug toxicity
- ↑ nephrotoxicity with aminoglycosides
- ↑ infection risk with other immunosuppressants