A randomized phase III multicenter trial of neoadjuvant docetaxel plus cisplatin and 5-fluorouracil (TPF) versus neoadjuvant PF in patients with locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN). Final analysis of EORTC 24971

Abstract

5516 Background: So far, the Wayne State regimen combining 100 mg/m2 cisplatin on day 1 and 1000 mg/m2/d continuous infusion 5-fluorouracil over 5 days (PF), is the gold standard in advanced SCCHN. Improvement of PF induction chemotherapy by adding a taxane has been suggested from phase II studies and 2 randomized phase III trials. We now report the final analysis of EORTC 24971. Methods: Eligible were patients (pts) with unresectable stage III/IV SCCHN (no distant metastases), 18 to 70 yrs of age, PS≤1, and adequate hematologic, renal and hepatic function. Pts were stratified by primary disease site (oral cavity, oropharynx, hypopharynx, larynx) and treatment center and randomized to PF (as above) or TPF (T 75 mg/m2/1h, P 75 mg/m2/1h, both d1, F 750 mg/m2/d, d1–5) q 3 wks, for 4 cycles unless progression (PD) or unacceptable toxicity, or refusal. Thereafter (interval 4–7 wks), all pts not in PD received radiotherapy (RT: conventional [66–70 Gy], accelerated [max. 70 Gy] / hyperfractionated [max. 74 Gy]). Surgery was allowed before RT (neck) or 3 months after RT (primary, neck). Primary endpoint was progression-free survival (PFS), and 348 pts and 260 events were needed to detect a 50% increase in median PFS (10 vs 15 mo) with 85% power. Results: Between April 1999 and March 2002, 358 pts were accrued (181 PF, 177 TPF). At a median follow-up (FUP) of 32 mo, PFS was significantly improved with TPF (HR 0.72, p = 0.0071; median 8.2 vs 11.0 mo). A 51 mo median FUP showed an overall survival (OS) benefit with TPF (HR 0.71, p = 0.0052; median 14.2 vs 18.6 mo). Estimated 3-yr survival rates are 23.9% (95% CI: 17.9%;30.5%) for PF and 36.5% (29.3%;43.6%) for TPF. Response rate also favored TPF (53.6% vs 67.8%, p = 0.006). There was more severe (G3+4) leucopenia (41.6% vs 22.9%) and neutropenia (76.9% vs 52.5%) with TPF, and more severe thrombocytopenia with PF (17.9% vs 5.2%). Severe alopecia occured more with TPF (55.5% vs 11.7%); hearing loss (2.8% vs 0%) and toxic death (7.8% vs 3.7%) more with PF. Conclusions: TPF (→ RT) is superior to PF (→ RT) for PFS, OS (including long-term), response rate, and is better tolerated. [Table: see text]