TPF Induction Chemotherapy in Head and Neck Cancer

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)