## Cetuximab as Alternative to Cisplatin in Concurrent Chemoradiation ### Clinical Context: Cisplatin-Ineligible Patients **Key Point:** Cetuximab (anti-EGFR monoclonal antibody) is the preferred alternative to cisplatin-based concurrent chemoradiation in patients with locally advanced oral cavity carcinoma who are cisplatin-ineligible [cite:Harrison 21e Ch 89]. ### Indications for Cetuximab - Renal impairment (eGFR <60 mL/min) — cisplatin contraindicated - Severe hearing loss or peripheral neuropathy — cisplatin ototoxic and neurotoxic - Cardiac dysfunction — cisplatin cardiotoxic - Poor performance status or advanced age ### Mechanism - Monoclonal antibody against EGFR (epidermal growth factor receptor) - Blocks ligand binding and receptor dimerization - Enhances radiosensitivity when combined with external beam radiation ### Dosing in Concurrent Chemoradiation - **Loading dose**: 400 mg/m² IV over 2 hours (week 1) - **Weekly maintenance**: 250 mg/m² IV over 1 hour (weeks 2–7 during radiation) - Total duration: 7–8 weeks concurrent with daily radiation ### Evidence Base **High-Yield:** The BONNER trial (2006) demonstrated that cetuximab + radiation improved 3-year overall survival (55% vs. 45%) compared to radiation alone in locally advanced head-and-neck cancers, establishing cetuximab as a standard alternative when cisplatin is contraindicated. ### Advantages Over Cisplatin Alternative - **Renal-safe**: No nephrotoxicity; safe in CKD - **No ototoxicity or peripheral neuropathy** - **Predictable toxicity profile**: Primarily skin rash (acneiform), diarrhea, infusion reactions **Clinical Pearl:** Acneiform rash occurs in ~80% of patients and correlates with better outcomes; prophylactic doxycycline or minocycline (100 mg BD) is recommended to minimize severity.
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