A 2-year-old girl with bilateral retinoblastoma (Group C in both eyes) is being planned for systemic chemotherapy. Which drug is the first-line agent for intra-arterial chemotherapy (IAC) in this scenario?

Explanation

## Intra-Arterial Chemotherapy (IAC) in Bilateral Retinoblastoma **Key Point:** Melphalan is the preferred agent for intra-arterial chemotherapy (IAC) in retinoblastoma because of its superior local delivery, high response rates, and ability to preserve vision in bilateral disease. ### Indications for IAC Intra-arterial chemotherapy is increasingly used for: - **Bilateral retinoblastoma** (to avoid bilateral enucleation or EBRT) - **Advanced intraocular disease** (Group C–E per International Classification) - **Chemotherapy-resistant tumors** after systemic chemoreduction - **Salvage therapy** before enucleation ### Why Melphalan for IAC? | Feature | Melphalan | Carboplatin | Cisplatin | | --- | --- | --- | --- | | **Route** | Intra-arterial (ophthalmic artery) | Systemic or intra-arterial | Systemic or intra-arterial | | **Local concentration** | Extremely high (100–1000× systemic) | Moderate | Moderate | | **Response rate** | 70–90% in Group C–D | 50–70% | 40–60% | | **Nephrotoxicity** | Minimal (local delivery) | Low | High (systemic) | | **Ototoxicity** | Minimal | Minimal | Significant (systemic) | | **Standard use** | **First-line IAC agent** | Adjunct or systemic | Adjunct or systemic | **High-Yield:** Melphalan achieves **globe salvage in 60–80% of eyes** with advanced retinoblastoma when delivered intra-arterially, making it the preferred agent for bilateral disease and chemotherapy-resistant tumors. ### Mechanism of IAC Advantage Intra-arterial delivery via the ophthalmic artery: 1. Delivers drug directly to the tumor vascular bed 2. Achieves 100–1000× higher intraocular concentrations than IV 3. Minimizes systemic toxicity (nephrotoxicity, ototoxicity) 4. Allows repeated cycles without cumulative organ damage **Clinical Pearl:** In bilateral retinoblastoma, sequential IAC to each eye (alternating every 3–4 weeks) can preserve both globes and vision, avoiding the devastating morbidity of bilateral enucleation or whole-brain radiotherapy in a young child. ### Typical IAC Protocol - **Agent:** Melphalan 0.4 mg/kg (max 10 mg) per eye - **Frequency:** Every 3–4 weeks - **Cycles:** 3–6 cycles depending on response - **Consolidation:** Followed by laser, cryotherapy, or brachytherapy as needed