A Phase II, Open-Label, Single-Arm trial to evaluate the combination of cetuximab plus taxotere, cisplatin, and 5-flurouracil (C-TPF) as an induction regimen in patients with unresectable squamous cell carcinoma of the head and neck (SCCHN)
Mené sur 50 patients atteints d'un carcinome épidermoïde non résécable de la tête et du cou (âge médian : 54 ans ; durée médiane de suivi : 40,7 mois), cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse objective, et la toxicité d'un traitement comportant une chimiothérapie d'induction par docétaxel-cisplatine-fluorouracile en combinaison avec le cétuximab, puis une radiothérapie accélérée en combinaison avec une radiothérapie concomitante de type boost et le cétuximab
Purpose : Despite treatment, prognosis of unresectable squamous cell carcinoma of the head and neck (SCCHC) is adverse. Cetuximab has proven to increase the clinical activity of radiotherapy and chemotherapy in patients with locoregional advanced disease with an acceptable toxicity profile. We designed a phase II trial to evaluate the efficacy of TPF plus cetuximab (C-TPF) as an induction regimen in patients with unresectable SCCHN. Methods and Materials : A single arm phase II trial was conducted. Eligible patients included those with untreated unresectable SCCHC, WHO performance status 0-1, age 18-70 yrs. Treatment consisted of four 21-day cycles of TPF (docetaxel 75mg/m2 d1, cisplatin 75mg/m2 d1, 5-fluorouracil 750mg/m2/d d1-5) and cetuximab at 250 mg/ m² weekly (loading dose 400 mg/ m²). Prophylactic G-CSF and antibiotic support were given. After induction, sequential accelerated radiotherapy with concomitant boost (69.9 Gy) and weekly cetuximab were delivered in the absence of disease progression. The primary endpoint was objective response rate (ORR) to C-TPF. Results : Fifty patients were enrolled across eight centers. Median age 54 years; all stage IV; oropharynx and hypopharynx were the most common primary sites. 82% received 4 cycles of C-TPF and 86% started sequential treatment based on radiotherapy and cetuximab. ORR after C-TPF was 86% (95% CI, 73% to 94%) and 24% were complete (CR). With a median follow-up of 40.7 months, median overall survival (OS) was 40.7 months. The 2-year actuarial locoregional control (LRC) rate was 57%. The most common drug-related grade 3/4 toxicities during induction were neutropenia (24%), neutropenic fever (24%), and diarrhea (20%).There were three treatment-related deaths (6%). Conclusions : C-TPF yields high ORR and CR as induction treatment in unresectable SCCHN. However, hematologic toxicity is too high to recommend this regimen at the current dose.
http://www.redjournal.org/article/S0360-3016%2815%2926584-4/abstract