Recommended Chemotherapy for Concurrent Chemoradiation in Head and Neck Cancer
High-dose cisplatin at 100 mg/m² administered intravenously every 3 weeks (on days 1,22, and 43) is the preferred Category 1 chemotherapy regimen for concurrent chemoradiation therapy in head and neck cancer. 1
Primary Treatment Setting (Definitive CCRT)
Single-agent cisplatin 100 mg/m² every 3 weeks is the standard regimen for patients receiving definitive concurrent chemoradiation, delivering 2-3 cycles depending on the radiation fractionation scheme (typically 70 Gy in 7 weeks at 2.0 Gy/fraction). 1, 2
- This regimen achieved superior laryngeal preservation rates (88% at 2 years) compared to induction chemotherapy (74%) or radiation alone (69%) in the landmark RTOG 91-11 trial, with sustained benefit at 10-year follow-up. 1
- The regimen is specifically recommended for locally advanced disease including T3-T4 tumors and N2-N3 nodal involvement. 1, 2
- IMRT is the preferred radiation technique to minimize dose to critical structures (salivary glands, temporal lobes, auditory structures). 2, 3
Postoperative Setting (Adjuvant CCRT)
Concurrent single-agent cisplatin at 100 mg/m² every 3 weeks for 3 doses is recommended for high-risk postoperative patients with extracapsular nodal extension and/or positive surgical margins. 1
- This recommendation is based on two pivotal trials (EORTC 22931 and RTOG 9501) demonstrating improved locoregional control and survival with postoperative chemoradiation versus radiation alone. 1, 2
- Radiation dose is typically 60-66 Gy at 2.0 Gy/fraction to high-risk regions. 3
- Treatment should begin as soon as possible after surgery, ideally within 6 weeks. 3, 4
Alternative Regimens
While other regimens exist, they are not preferred:
- Weekly cisplatin (40 mg/m² weekly): Increasingly used in practice with emerging evidence of non-inferiority for disease outcomes and reduced toxicity. 5, 6 However, this lacks the robust prospective validation of the three-weekly regimen and is not designated as Category 1 by NCCN guidelines. 1
- Carboplatin plus 5-FU: The GORTEC 99-02 trial used standard fractionation plus 3 cycles of carboplatin/5-FU, showing efficacy. 1 However, cisplatin remains preferred due to superior activity. 7
- Cetuximab: FDA-approved for combination with radiation in locally advanced SCCHN, but not considered equivalent to cisplatin-based regimens for most patients. 8
Critical Implementation Considerations
Cumulative cisplatin dose threshold: A minimum cumulative dose of 200 mg/m² is generally regarded as necessary for beneficial anti-tumor effect. 5, 7 Approximately 40% of patients fail to receive all three cycles of high-dose cisplatin, making compliance monitoring essential. 5
Toxicity profile: High-dose cisplatin carries significant toxicity burden including:
- Grade 3/4 mucositis (33%), dermatitis (41%), dysphagia (15%) 6
- Hematologic suppression, renal impairment (3%), nausea/vomiting 6, 9
- Cardiopulmonary arrest risk requiring electrolyte monitoring (magnesium, potassium, calcium) 8
- Treatment-related mortality (reported 3/30 patients in stage IV disease) 9
Patient selection is critical: Not all patients can tolerate concurrent therapy. 2 Stage IV unresectable disease showed particularly high toxicity rates with prolonged treatment times (median 63 days) and frequent treatment breaks. 9 Aggressive supportive care including antiemetics, hydration, nutritional support, and close monitoring is mandatory. 1, 2
Common Pitfalls to Avoid
- Inadequate supportive care: Chemoradiation requires an experienced multidisciplinary team with substantial supportive care infrastructure. 1
- Dose reductions without cause: Maintain the 100 mg/m² dose unless specific toxicities mandate reduction per protocol. 1
- Delayed treatment initiation: In the postoperative setting, delays beyond 6 weeks compromise outcomes. 3, 4
- Ignoring cumulative dose: If a patient cannot complete at least 200 mg/m² cumulative cisplatin, consider alternative strategies early. 5, 7