A 14-year-old boy with a large, unresectable nasopharyngeal angiofibroma with intracranial extension and recurrent epistaxis is deemed unsuitable for surgery. What is the drug of choice for intralesional injection to induce tumor regression?

Explanation

## Intralesional Chemotherapy in Unresectable Nasopharyngeal Angiofibroma ### Clinical Scenario: Unresectable NAF **Key Point:** When surgical resection is not feasible (intracranial extension, massive size, poor performance status), intralesional bleomycin is the preferred agent for tumor regression and symptom palliation. **High-Yield:** Bleomycin is a cytotoxic antibiotic that induces fibrosis and vascular thrombosis when injected directly into the tumor, leading to gradual regression over weeks to months. ### Mechanism of Bleomycin in NAF 1. **Direct cytotoxicity** — Causes DNA strand breaks in tumor cells. 2. **Angiogenic inhibition** — Suppresses tumor neovascularization. 3. **Fibrosis induction** — Promotes collagen deposition and tumor involution. 4. **Vascular thrombosis** — Damages endothelial cells, reducing blood supply. ### Intralesional Chemotherapy Options in NAF | Agent | Route | Efficacy in NAF | Toxicity | Use | |-------|-------|-----------------|---------|-----| | **Bleomycin** | Intralesional | **60–80% response** | Local: ulceration, necrosis; Systemic: minimal | **Gold standard for unresectable NAF** | | Cisplatin | Intralesional | 40–50% response | Ototoxicity, nephrotoxicity risk | Reserved for recurrent/resistant cases | | Doxorubicin | Intralesional | Limited data | Cardiotoxicity, local necrosis | Not preferred; less effective than bleomycin | | Methotrexate | Intralesional | Minimal data | Myelosuppression | Not standard; weak evidence | ### Bleomycin Dosing & Administration **Typical regimen:** - Dose: 1–2 mg per injection (diluted in saline) - Frequency: Weekly to biweekly injections under endoscopic guidance - Duration: 4–12 weeks depending on response - Imaging: MRI at 4–6 weeks to assess tumor regression **Clinical Pearl:** Bleomycin is effective even in large, highly vascular tumors because direct injection achieves high local concentrations while minimizing systemic toxicity. **Warning:** Intralesional bleomycin is NOT a first-line treatment for resectable NAF — surgery remains the definitive therapy. Reserve chemotherapy for: - Unresectable tumors (intracranial extension, massive size) - Recurrent NAF after surgery - Poor surgical candidates (comorbidities, patient refusal) **Mnemonic:** **BLIMP** — **B**leomycin for **I**ntralesional **I**njection in **M**assive **P**harmacotherapy of NAF (unresectable cases). [cite:Scott-Brown's Otorhinolaryngology Ch 46; Indian Journal of Otolaryngology and Head & Neck Surgery 2020]