Based on the TAX 324 study published in NEJM, the following represents a comprehensive treatment protocol for TPF (docetaxel, cisplatin, fluorouracil) induction chemotherapy for locally advanced squamous cell carcinoma of the head and neck.

https://www.nejm.org/doi/full/10.1056/NEJMoa070956

Pre-Treatment Assessment Parameters

1. Baseline Evaluation:

  • Complete history and physical examination
  • Performance status assessment (WHO/ECOG ≤1 required)
  • Baseline audiometry
  • Nutritional assessment; consider prophylactic PEG placement
  • Dental evaluation and necessary interventions

2. Laboratory Tests:

  • Complete blood count with differential
  • Comprehensive metabolic panel including:
      • Renal function (creatinine clearance ≥60 mL/min)
      • Liver function tests (AST, ALT, bilirubin ≤1.5× ULN)
      • Electrolytes including magnesium, calcium, and phosphate
      • Baseline albumin level

3. Imaging Studies:

  • CT or MRI of head and neck
  • CT of chest
  • PET-CT (optional, for baseline staging)

TPF Chemotherapy Regimen

Repeat cycle every 21 days for 3 cycles:

1. Day 1:

  • Docetaxel 75 mg/m² IV over 1 hour
  • Followed by cisplatin 100 mg/m² IV over 1-3 hours
  • Begin fluorouracil 1000 mg/m²/day as continuous IV infusion

2. Days 2-4:

  • Continue fluorouracil 1000 mg/m²/day as continuous IV infusion (total 4-day infusion)

 

Pre-Medications

1. Docetaxel Pre-Medications (start 12-24 hours prior to docetaxel):

  • Dexamethasone 8 mg PO BID for 3 days starting 1 day before chemotherapy
  • Diphenhydramine 25-50 mg IV 30 minutes before docetaxel
  • Ranitidine 50 mg IV (or equivalent H2 blocker) 30 minutes before docetaxel

2. Cisplatin Pre-Medications:

  • Ondansetron 16 mg IV or palonosetron 0.25 mg IV day 1
  • Dexamethasone 20 mg IV day 1 (can be integrated with docetaxel premedication)
  • Aprepitant 125 mg PO day 1, followed by 80 mg PO days 2-3
  • Olanzapine 5-10 mg PO day 1 (optional for high-risk patients)

 

IV Hydration Protocol

1. Pre-Cisplatin Hydration:

  • Normal saline 1000-1500 mL with 20 mEq KCl and 2 g magnesium sulfate over 2-3 hours

2. Post-Cisplatin Hydration:

  • Normal saline 1000-1500 mL with 20 mEq KCl and 2 g magnesium sulfate over 2-3 hours
  • Continue IV hydration for 24-48 hours if outpatient administration not feasible

3. Mannitol Diuresis (optional):

  • Mannitol 12.5-25 g IV before cisplatin

 

Supportive Care Medications

1. Prophylactic Antibiotics:

  • Ciprofloxacin 500 mg PO BID (or levofloxacin 500 mg daily) starting day 5 of each cycle for 10 days

2. G-CSF Support (consider for high-risk patients):

  • Pegfilgrastim 6 mg SC once on day 6, or
  • Filgrastim 5 μg/kg SC daily starting day 5 until ANC recovery

3. Home Antiemetic Regimen:

  • Days 1-4: Dexamethasone 8 mg PO BID (tapering schedule)
  • Days 2-3: Aprepitant 80 mg PO daily
  • Days 1-7: Ondansetron 8 mg PO Q8H PRN or 8 mg ODT Q12H PRN
  • PRN: Prochlorperazine 10 mg PO/IV Q6H or metoclopramide 10-20 mg PO/IV Q6H
  • PRN: Olanzapine 5-10 mg PO daily for breakthrough nausea
  • PRN: Lorazepam 0.5-1 mg PO/IV Q6H for anticipatory nausea/anxiety

 

Laboratory Monitoring

1. Before Each Cycle:

  • CBC with differential (ANC ≥1,500/μL, platelets ≥100,000/μL required)
  • Comprehensive metabolic panel
  • Magnesium, calcium, phosphate levels
  • Creatinine clearance calculation

2. During Treatment:

  • CBC weekly during cycles
  • Electrolytes twice weekly when receiving cisplatin
  • Liver function tests weekly for first cycle, then before each subsequent cycle

 

Dose Modifications

1. Hematologic Toxicities:

  • Grade 4 neutropenia lasting >7 days: Reduce docetaxel to 60 mg/m²
  • Febrile neutropenia: Reduce docetaxel to 60 mg/m²
  • Grade 4 thrombocytopenia: Reduce cisplatin and fluorouracil by 25%

2. Non-Hematologic Toxicities:

  • Grade 3-4 mucositis: Reduce fluorouracil by 25%
  • Creatinine clearance 40-59 mL/min: Reduce cisplatin to 75 mg/m²
  • Creatinine clearance <40 mL/min: Consider carboplatin substitution
  • Grade 2 neuropathy: Reduce cisplatin by 25%
  • Grade 3 neuropathy: Discontinue cisplatin

 

Post-Induction Therapy

As per the TAX 324 protocol, 3-8 weeks after the third cycle of induction chemotherapy, patients should proceed to:

  • Chemoradiotherapy with weekly carboplatin (AUC 1.5)
  • Definitive radiotherapy (70-74 Gy to primary tumor, 60-74 Gy to involved nodes, ≥50 Gy to uninvolved nodes)