Could the addition of Cetuximab to conventional radiotherapy improve organ preservation in those patients with locally-advanced larynx cancer and who respond to induction chemotherapy ? An organ preservation TTCC phase II study
Mené sur 93 patients atteints d'un carcinome du larynx de stade III à IVA (durée médiane de suivi : 53,7 mois), cet essai multicentrique de phase II évalue l'efficacité, du point de vue des taux actuariels de survie avec larynx fonctionnel, de survie sans laryngectomie et de survie globale à 3 ans, et la toxicité d'une chimiothérapie d'induction par docétaxel-cisplatine-fluorouracile suivie d'une radiothérapie en combinaison avec le cétuximab
Background : Induction chemotherapy (IC) with docetaxel/cisplatin/fluorouracil (TPF) is superior to platinum/fluorouracil (PF) in organ preservation. Bioradiotherapy (BRT) is superior to radiotherapy (RT) alone in the loco-regional control of locally advanced head and neck tumors. The aim of our study was to evaluate the efficacy and safety of IC followed by BRT to achieve functional larynx preservation. Patients and Methods : The current study was a phase II, open-label, multicenter study of patients with stage III and IVA laryngeal carcinoma and candidates for total laryngectomy (TL). Main objective: survival with functional larynx (SFL) rate at 3 years. Critical value to consider study positive: SFL >59%. Patients received 3 cycles of IC with TPF and those who responded received conventional BRT with cetuximab. In patients with residual nodal disease after BRT, neck dissection was planned 2 months after BRT. Patients who did not respond to IC underwent TL + neck dissection + RT. Results : A total of 93 patients started TPF. Responses to IC on larynx target lesion: 37 (40%) patients showed a complete response; 38 (41%) patients showed a partial response; 8 (9%) patients showed stabilization (SD); 2 (2%) patients showed progressive disease and 8 (9%) patients were not evaluated (2 deaths, 5 adverse events (AEs), and 1 lost follow-up). Seventy-three (78%) patients received BRT: 72 as per protocol, but 1 with only SD. Median follow-up was 53.7 months. Three-year actuarial rates: SFL: 70% (95% CI: 60-79%); laryngectomy-free survival: 72% (95% CI: 61-81%); overall survival: 78% (95% CI: 63-82%). The acute toxicity observed during both IC and BRT was as expected, with only 1 toxicity-related death (local bleeding) during BRT. Conclusions : According to this protocol, the SFL rate was clearly higher than the critical value with acceptable levels of toxicity. The role of cetuximab added to radiotherapy in patients with stage III and IVA laryngeal cancer who respond to TPF could improve functional larynx preservation. A phase III trial is warranted.