Induction TPF in Oral Cavity Cancer
Induction TPF chemotherapy is NOT recommended for oral cavity cancer and does not improve survival compared to upfront surgery followed by adjuvant therapy. 1
Evidence-Based Recommendation
The highest quality guideline evidence explicitly states that outside of a laryngeal-preservation strategy, the role of induction chemotherapy is not recommended for head and neck cancers, including oral cavity tumors. 1 This is a Level I, Grade A recommendation from the EHNS-ESMO-ESTRO 2020 guidelines.
Key Supporting Evidence:
Induction chemotherapy followed by concurrent chemoradiotherapy for non-laryngeal or hypopharyngeal tumors has not been shown to be superior to concurrent chemoradiotherapy alone 1
Primary surgical treatment followed by adjuvant radiotherapy or chemoradiotherapy is the preferred treatment for T3/T4 oral cavity cancers 1, 2
The most recent randomized phase III trial specifically in oral cavity cancer (2013) demonstrated that TPF induction followed by surgery showed no survival benefit compared to upfront surgery (HR 0.977,95% CI 0.634-1.507, P=0.918) 3
Why TPF Fails in Oral Cavity Cancer
Lack of Survival Benefit:
A 2016 meta-analysis of 1,022 patients showed TPF induction before chemoradiotherapy did not improve overall survival (HR 1.010,95% CI 0.84-1.21, p=0.92) or progression-free survival (HR 0.91,95% CI 0.75-1.1, p=0.32) 4
Only 19.4% of patients in this meta-analysis had oral cavity primaries, but the negative results applied across all subsites 4
Substantial Toxicity Without Benefit:
Treatment-related mortality ranges from 9.5% to 15.3% in oral cavity cancer patients receiving TPF 5, 6
38.2% of patients were unable to complete or receive planned definitive therapy after induction TPF in one series 6
The overall toxicity of induction followed by chemoradiotherapy can be substantial, compromising final results 1
Correct Treatment Algorithm for Oral Cavity Cancer
Early Stage Disease (T1-T2, N0-N1):
- Single-modality treatment with surgery or radiotherapy 2
- Conservative surgery (transoral laser microsurgery or transoral robotic surgery) is preferred 2
Locally Advanced Disease (T3-T4 or N2-N3):
- Primary surgical resection followed by risk-adapted adjuvant therapy 1, 2
- Postoperative radiotherapy (58-64 Gy) for: pT3-4 tumors, perineural infiltration, lymphovascular invasion, >1 positive node 1, 2
- Postoperative chemoradiotherapy (66 Gy with cisplatin 100 mg/m² every 3 weeks) for: R1 resection or extracapsular extension 1, 2
Critical Caveats
When TPF IS Indicated:
- TPF is the standard induction regimen ONLY for laryngeal or hypopharyngeal cancer in organ-preservation strategies 1
- TPF is FDA-approved for induction treatment of locally advanced squamous cell carcinoma of the head and neck, but this does not mean it improves outcomes in oral cavity primaries 7
Populations at Highest Risk:
- Low socioeconomic status patients have 15.3% mortality during therapy with TPF 6
- Patients with Karnofsky performance status <80 have significantly higher mortality (P=0.04) 6
- Elderly patients (≥65 years) experience higher rates of diarrhea, infection, peripheral edema, and stomatitis with TPF 7
Common Pitfall to Avoid:
Do not extrapolate laryngeal preservation data to oral cavity cancer—the biology and treatment paradigms are fundamentally different. Oral cavity cancers require surgical extirpation as the primary modality, and delaying surgery with ineffective induction chemotherapy increases morbidity and mortality without improving outcomes. 1, 3