What is the recommended treatment regimen for a patient with laryngeal cancer undergoing high dose concurrent chemoradiation therapy (CCRT), including the number of chemotherapy cycles and specific chemotherapy agents such as cisplatin and 5-fluorouracil?

High-Dose Concurrent Chemoradiation for Laryngeal Cancer: Number of Chemotherapy Cycles

For high-dose concurrent chemoradiation (CCRT) in laryngeal cancer, 3 cycles of cisplatin at 100 mg/m² given every 3 weeks (on days 1,22, and 43) should be administered, as this represents the evidence-based standard that achieved superior larynx preservation rates (88% at 2 years) compared to alternative regimens. 1, 2

Evidence-Based Dosing Regimen

The landmark Intergroup Head and Neck Trial (RTOG 91-11) established the standard concurrent chemoradiation approach for laryngeal preservation 1:

• High-dose cisplatin at 100 mg/m² administered on days 1,22, and 43 concurrent with 70 Gy radiation to the primary site achieved 88% larynx preservation at 2 years and 84% at 5 years 1
• This regimen demonstrated significantly superior locoregional control (78%) compared to induction chemotherapy followed by radiation (61%) or radiation alone (56%) 2
• Three cycles are standard because radiation therapy typically extends 7 weeks, allowing for cisplatin administration at 3-week intervals 1

Why Not 2 Cycles?

The Cleveland Clinic Trial used only 2 cycles of cisplatin/fluorouracil concurrent with radiation, but this achieved inferior outcomes 1:

• Larynx preservation rate of only 29% at 5 years with 2 cycles versus 88% at 2 years with 3 cycles of high-dose cisplatin 1
• The 2-cycle regimen used cisplatin/fluorouracil combination rather than single-agent high-dose cisplatin 1

Cumulative Dose Target

The goal is to achieve a cumulative cisplatin dose of at least 200 mg/m² to optimize outcomes 1:

• Three cycles of 100 mg/m² = 300 mg/m² total, well exceeding the minimum threshold 1
• Achieving optimum cisplatin dose intensity correlates significantly with better disease-free survival, overall survival, and larynx preservation survival 3

Alternative Dosing When High-Dose Not Feasible

If the patient cannot tolerate 100 mg/m² every 3 weeks 1:

• Weekly cisplatin at 40 mg/m² for 7 doses is an acceptable alternative, still targeting cumulative dose ≥200 mg/m² (280 mg/m² total) 1
• This requires 7 administrations rather than 3, but may be better tolerated in patients with borderline performance status 1

Critical Caveats

Treatment completion is challenging but essential 3:

• Only 61.9% of patients in one series achieved optimum doses of both chemotherapy and radiation 3
• Grade 3-4 toxicities occur in 81-82% of patients receiving concurrent chemoradiation versus 61% with radiation alone 2
• Mucosal toxicity with concurrent cisplatin is nearly twice as frequent as other regimens during radiation 2

Patient selection determines success 1:

• Patients with tumor penetration through cartilage into soft tissues are poor candidates for organ preservation and should undergo primary total laryngectomy 1
• Continued cigarette smoking is associated with worse outcomes; patients must abstain throughout treatment 1

Induction Chemotherapy Context

Do not confuse induction with concurrent regimens 1, 4:

• Induction chemotherapy uses 3 cycles of TPF or cisplatin/5-FU administered before radiation, not concurrently 1, 4
• The RTOG 91-11 trial showed concurrent cisplatin was superior to induction followed by radiation for larynx preservation (88% vs 75% at 2 years) 1, 2
• Induction's only established role is selecting patients for organ preservation in those who would otherwise require total laryngectomy 5, 4