When is Cisplatin + 5-Fluorouracil (5FU)/Docetaxel used in head and neck cancer?

When to Use Cisplatin + 5FU/Docetaxel in Head and Neck Cancer

Cisplatin + 5-Fluorouracil + Docetaxel (TPF regimen) is primarily indicated as induction chemotherapy for locally advanced squamous cell carcinoma of the head and neck (SCCHN) in patients with good performance status (PS 0-1), though this remains a category 3 recommendation with significant controversy regarding its role compared to concurrent chemoradiation alone. 1, 2, 3

Primary Indication: Induction Chemotherapy for Locally Advanced Disease

Patient Selection Criteria

• Performance status 0-1 is essential for TPF induction therapy 1
• Locally advanced disease (Stage III-IV) that is technically resectable but where organ preservation is desired 1, 2
• Patients with T4a tumors who decline surgery may be considered for induction chemotherapy 1

The Induction Chemotherapy Controversy

• Major disagreement exists among guideline panels about whether TPF induction followed by radiotherapy or chemoradiation should be used, reflected in the NCCN category 3 recommendation 1
• TPF shows superior response rates, disease-free survival, and overall survival compared to the older cisplatin/5-FU doublet (PF regimen) 1, 2
• However, no clear advantage in overall survival has been demonstrated when adding TPF induction before concurrent chemoradiation compared to concurrent chemoradiation alone 1
• Approximately 3 times as many patients were excluded from efficacy assessments on induction arms in randomized trials, suggesting potential toxicity concerns 1

Standard TPF Dosing Regimen

• Docetaxel 75 mg/m² day 1, Cisplatin 75-100 mg/m² day 1,5-FU 750-1000 mg/m²/day continuous infusion days 1-5, repeated every 3 weeks for 3 cycles 3, 4, 5
• Must be followed by definitive local therapy (radiotherapy or concurrent chemoradiation) 1
• Prophylactic antibiotics and G-CSF are recommended for all patients receiving TPF 3

Secondary Indication: Recurrent/Metastatic Disease

First-Line Palliative Treatment

• Cisplatin or carboplatin + 5-FU + cetuximab is the preferred category 1 regimen for recurrent/metastatic non-nasopharyngeal SCCHN, improving median survival to 10.1 months versus 7.4 months with platinum/5-FU alone 1, 2, 6
• Cisplatin or carboplatin + taxane (docetaxel or paclitaxel) is an alternative combination regimen 1, 2
• Cisplatin + 5-FU without cetuximab shows higher response rates but no survival benefit compared to single agents 1

Patient Selection for Palliative Therapy

• Good performance status (PS 0-1) required for combination regimens 1
• PS 2-3 patients should receive less intensive regimens or single-agent therapy 1, 2

Critical Caveats and Pitfalls

Toxicity Concerns

• All TPF regimens cause significant toxicity: grade 3-4 neutropenia (42-78%), febrile neutropenia (4-15%), mucositis (24%), diarrhea, peripheral neuropathy, and sodium-wasting nephropathy 4, 7, 5
• Treatment-related mortality of 4% has been reported with TPF induction 5
• Close monitoring by an experienced multidisciplinary team is mandatory 1

Feasibility After Induction

• High-dose cisplatin (100 mg/m² every 21 days × 3) may not be feasible for many patients after TPF induction 1
• Uncertainty exists about which concurrent regimen should follow induction (weekly cisplatin, taxanes, cetuximab, or combinations) 1
• Risk that efficacy gains from induction may be offset by less effective or poorly tolerated subsequent concurrent therapy 1

Age Considerations

• Patients over 65 years show significantly lower dose intensity but similar progression-free survival, requiring careful dose modification 5

When NOT to Use TPF

• Concurrent chemoradiation with high-dose cisplatin alone remains the standard category 1 treatment for locally advanced disease in patients with PS 0-1 1, 2
• Early-stage disease (T1-2, N0-1) does not require induction chemotherapy 1
• Patients with PS 2-3 should not receive TPF 1
• Prior radiotherapy or poor organ function are relative contraindications 3