Standard cisplatin/infusional 5-fluorouracil (PF) vs docetaxel (T) plus PF (TPF) as neoadjuvant chemotherapy for nonresectable locally advanced squamous cell carcinoma of the head andneck (LA-SCCHN): a phase III trial of the EORTC Head and Neck Cancer Group (EORTC #24971)

Abstract

5508 Background: Data from 5 phase II studies support the notion that T may add to the efficacy of PF in LA-SCCHN (Posner et al. ASCO 20: 203b, 2001). Based on our phase I-II experience with TPF (Schrijvers et al. Ann Oncol 15: 638, 2004), we undertook a phase III trial comparing TPF with PF in such patients (pts). Methods: Eligible pts included nonresectable LA-SCCHN (excluding nasopharynx, nasal & paranasal cavities), measurable disease, adequate organ function, WHO performance status (PS) 0–1, age 18–70 yrs, signed informed consent. Stratification included primary tumor site and institution. Treatment arms were: Arm 1 (PF): P 100 mg/m2 day (d) 1, then F 1000 mg/m2 CI d1–5 q 21 d; Arm 2 (TPF): T 75 mg/m2 d1, P 75 mg/m2 d1, then 5-FU 750 mg/m2 CI d1–5 q 21 d. Planned treatment included 4 cycles unless progression (PD), unacceptable toxicity or pt refusal. Thereafter (interval 4–7 wks), all pts received protocol defined radiotherapy (RT: conventional, accelerated/ hyperfractionated) unless PD after cycle 1 or 2. Surgery before RT (neck dissection) or 3 months (mo) after RT (residual disease) was permitted. The planned sample size of 348 pts and 260 events had 85% power to detect a hazard ratio (HR) of 0.67 (median 10 vs 15 mo) for the primary endpoint of progression-free survival (PFS), using a 5% 2-sided test. Results: 358 pts were accrued (181 to PF and 177 to TPF). Pt/tumor characteristics (age, sex, PS, primary site, T&N stage) were well balanced. After a median follow-up of 32 mo, TPF demonstrated significantly superior PFS (HR 0.72; [95% CI 0.56;0.91]; p=0.006), overall survival (HR 0.73; [95% CI 0.57; 0.94]; p=0.016) and response rate (RR: 67.8% vs 53.6%; p=0.007), while the PF arm showed greater grade 3–4 nausea (7.3% vs 0.6%), vomiting (5.0% vs 0.6%) and stomatitis (11.2% vs 4.6%) and more toxic deaths (5.5% vs 2.3%). Conclusions: TPF (→RT) is superior to PF (→RT) in terms of RR, PFS, OS and is better tolerated. No significant financial relationships to disclose.