Carboplatin Overview
- Class: Platinum-based alkylating agent
- Mechanism of Action:
Carboplatin forms intra- and inter-strand DNA crosslinks by binding to nucleophilic sites (mainly N7 of guanine), disrupting DNA synthesis and function, leading to apoptosis.
Indications (Selected):
- Ovarian cancer (FDA-approved)
- Also used off-label for:
Dosing:
- Calvert Formula (Preferred): Dose (mg)=Target AUC×(GFR+25)text{Dose (mg)} = text{Target AUC} times (text{GFR} + 25)
- AUC target typically ranges from 4–6 for combination therapy, 6–7.5 for monotherapy.
- GFR estimation can use Cockcroft-Gault or measured creatinine clearance.
- Note: GFR often capped at 125 mL/min to reduce risk of overexposure.
- Important: Always confirm baseline renal function, as carboplatin clearance is highly dependent on renal function.
Toxicities:
- Hematologic (dose-limiting):
- Thrombocytopenia (most prominent)
- Neutropenia, anemia
- Nadir ~21 days post-treatment, recovery by ~28 days
- Non-Hematologic:
- Nausea and vomiting (moderate emetogenic risk)
- Hypersensitivity reactions (risk increases after multiple cycles; may require desensitization)
- Less nephrotoxicity, neurotoxicity, and ototoxicity compared to cisplatin
Drug Interactions:
- Nephrotoxic agents: May increase toxicity (e.g., aminoglycosides, NSAIDs)
- Myelosuppressive agents: May enhance hematologic toxicity
Supportive Care Considerations:
- Antiemetic prophylaxis: Based on moderate emetogenic risk guidelines
- CBC monitoring: Prior to each cycle; delay/reduce dose if prolonged cytopenias
- Renal function monitoring: Especially important for accurate dosing
Other Notes:
- Formulation: Solution for injection; stable for short time after reconstitution
- Administration: IV over 15–60 minutes; can be given as part of many combination regimens
- Handling: Follow cytotoxic handling precautions