Background
Phase III RCT (GORTEC 2000-01) of 220 patients with operable, untreated stage III/IV larynx or hypopharynx invasive squamous cell carcinoma requiring total laryngectomy. Larynx-preservation induction strategy comparing two regimens. This is the long-term (5- and 10-yr) follow-up report.
Interventions and follow up
Arm A (TPF): docetaxel 75 mg/m2 D1, cisplatin 75 mg/m2 D1, 5-FU 750 mg/m2/d by 24-h continuous infusion x5d
Arm B (PF): cisplatin 100 mg/m2 D1 plus 5-FU 1000 mg/m2/d by 24-h continuous infusion x5d
Post-induction: patients with CR/PR plus recovered laryngeal motility received RTx 3-7 wk after last chemotherapy; non-responders underwent total laryngectomy with neck dissection and adjuvant RTx +/- chemo
Primary endpoint: larynx preservation rate (LPR) and overall response (OR)
mFollow up: >105 months (long-term analysis)
Arm B (PF): cisplatin 100 mg/m2 D1 plus 5-FU 1000 mg/m2/d by 24-h continuous infusion x5d
Post-induction: patients with CR/PR plus recovered laryngeal motility received RTx 3-7 wk after last chemotherapy; non-responders underwent total laryngectomy with neck dissection and adjuvant RTx +/- chemo
Primary endpoint: larynx preservation rate (LPR) and overall response (OR)
mFollow up: >105 months (long-term analysis)
Results
3-yr LPR: 70.3% vs 57.5% (TPF vs PF); difference 12.8%; P=.03
5-yr LPR: 74.0% vs 58.1%
10-yr LPR: 70.3% vs 46.5%; P=.01
OR: 80.0% vs 59.2%; difference 20.8%; P=.002
5-yr OS: 50.9% vs 41.9%; HR 1.08, 95% CI 0.71-1.63
10-yr OS: 30.2% vs 23.5%; HR 1.07, 95% CI 0.74-1.57 (no significant OS difference)
5-yr LPR: 74.0% vs 58.1%
10-yr LPR: 70.3% vs 46.5%; P=.01
OR: 80.0% vs 59.2%; difference 20.8%; P=.002
5-yr OS: 50.9% vs 41.9%; HR 1.08, 95% CI 0.71-1.63
10-yr OS: 30.2% vs 23.5%; HR 1.07, 95% CI 0.74-1.57 (no significant OS difference)
Adverse events
Treatment-related deaths: 5 patients died of acute toxicity during induction – 3 in TPF (2 diarrhea/dehydration, 1 GI bleed) and 2 in PF (1 AKI, 1 infection)
Grade 4 hematologic (TPF vs PF): neutropenia 31.5% vs 17.6%; febrile neutropenia 10.9% vs 5.8%; thrombocytopenia 1.8% vs 7.8%
Other grade 3-4: stomatitis 4.6% vs 7.8%; creatinine elevation 0% vs 2.0%
Grade 4 hematologic (TPF vs PF): neutropenia 31.5% vs 17.6%; febrile neutropenia 10.9% vs 5.8%; thrombocytopenia 1.8% vs 7.8%
Other grade 3-4: stomatitis 4.6% vs 7.8%; creatinine elevation 0% vs 2.0%
Conclusions
In advanced larynx and hypopharynx carcinoma, TPF induction chemotherapy was superior to PF for larynx preservation and overall response, with durable LPR benefit at 10 years and no OS difference. Larynx preservation can be achieved in a higher proportion of patients with TPF induction.
Key Limitations
Modest sample size (n=220) underpowered to detect OS differences; open-label design; predates routine HPV/p16 stratification and modern IMRT and immunotherapy; toxic deaths during induction underscore patient-selection importance.
Clinical Context
Supports TPF as the preferred induction backbone over PF for larynx-preservation candidates, building on the earlier GORTEC 2000-01 primary report. ESMO larynx-preservation guidance recognizes induction TPF followed by RT as an option for organ preservation in advanced larynx/hypopharynx cancer.