ABSTRACT
PURPOSE: To evaluate the efficacy and safety of induction chemotherapy (IC) followed by bioradiotherapy (BRT) to achieve functional larynx preservation in the setting of locally advanced head and neck tumors. METHODS AND MATERIALS: This was a phase 2, open-label, multicenter study of patients with stage III and IVA laryngeal carcinoma who were candidates for total laryngectomy. The primary endpoint was the rate of survival with functional larynx (SFL) at 3 years, with a critical value to consider the study positive of SFL >59%. Patients received 3 cycles of IC with TPF (docetaxel, cisplatin, and 5-fluorouracil), 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 total laryngectomy plus neck dissection and radiation therapy. RESULTS: A total of 93 patients started TPF. Responses to IC on larynx target lesion were as follows: 37 patients (40%) showed a complete response; 38 patients (41%) showed a partial response; 8 patients (9%) showed stabilization; 2 patients (2%) showed progressive disease, and 8 patients (9%) were not evaluated (2 deaths, 5 adverse events, and 1 lost to follow-up). Seventy-three patients (78%) received BRT: 72 as per protocol, but 1 with only stable disease. Median follow-up was 53.7 months. Three-year actuarial rates were as follows: SFL: 70% (95% confidence interval [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 use of cetuximab added to radiation therapy in patients with stage III and IVA laryngeal cancer who respond to TPF could improve functional larynx preservation. A phase 3 trial is warranted.
