Randomized phase III trial comparing induction chemotherapy using cisplatin (P) fluorouracil (F) with or without docetaxel (T) for organ preservation in hypopharynx and larynx cancer. Preliminary results of GORTEC 2000–01

Abstract

5506 Background: Induction chemotherapy (CT) with PF followed by RT in case of objective response is an alternative to total laryngectomy (TL) for patients with locally advanced larynx (L) and hypopharynx (H) cancer. Data have suggested that T may add to the efficacy of PF. The objective of this trial was to determine whether the addition of T to PF could increase the L preservation rate. Methods: Patients with L and H cancer for whom surgical procedure required TL were randomized to receive PF or TPF. Inclusion criteria were: adequate organ function, WHO PS 0 or 1, age from 18 to 70, signed informed consent. Treatment arms were PF = P 100 mg/m2/d1 and F: 1000 mg/m2 continuous infusion (CI) d1 to 5, TPF = T: 75 mg/m2/d1, P: 75mg/m2/d1 and F: 750mg/m2 CI d1 to 5 for 3 cycles with 21 days interval. Patients with complete or partial response and who recovered normal L mobility received RT to 70 Gy. Non responders underwent TL followed by RT. The primary endpoint was 3-year larynx preservation rate. To detect an absolute difference of 15% the sample size was 210. Results: 220 patients were randomized (108 to PF, 112 to TPF). Patients characteristics (age, sex, PS, primary site, TN) were well balanced. The TPF arm showed greater grade 3–4 alopecia (19% vs 2%) and neutropenia (57% vs 35%) while the PF arm showed greater grade 3–4 mucositis (9% vs 4%) and febrile neutropenia (6% vs 2%).Compliance to CT was better in the TPF. The specified treatment was delivered in 81.2% of patients in the TPF vs 67.4%. The overall response rate (T and N) was 82.8% in the TPF vs 60.8% (p = 0.0013). 60.6% of patients achieved a complete endoscopic response vs 46.7%. L preservation was offered for 80% of patients in the TPF vs 57.6%. A high hemoglobin level (>14 gr/l) and a compliance to treatment >80% are associated with a better response rate. With a median follow up of 35 months the 3-year actuarial L preservation rate is 73% following TPF vs 63% using the PF regimen. Conclusion: In advanced L and H cancer, TPF demonstrated significantly superior overall response rate compared to the PF regimen. The TPF is better tolerated and preliminary results suggest that L preservation could be achieved for a higher proportion of patients. No significant financial relationships to disclose.