Phase II study of induction chemotherapy followed by concomitant chemoradiotherapy in advanced head and neck cancer: clinical response and organ/function preservation.

We planned to conduct a trial of induction chemotherapy followed by concomitant chemoradiotherapy with the goal of organ-function preservation in advanced head and neck cancer patients with the response rate and local control of disease as primary endpoints and the assessment of toxicity as secondary endpoint. The overall treatment plan consisted of 3 cycles, each q. 28 days, of induction chemotherapy with cisplatin, 5-FU, leucovorin and interferon alpha2b (PFL-IFN), followed by response evaluation and local therapy with concomitant chemoradiotherapy with 5-FU, hydroxyurea and concomitant radiotherapy (FHX). The evaluation of clinical response was performed during the 2nd week after the 3rd cycle of induction chemotherapy and FHX was initiated 28 days after the 3rd cycle of induction chemotherapy. Hydroxyurea was administered orally at doses of 1 g every 12 h x 11, 5-FU was administered on days 1 through 5 at 800 mg/m2/d for 5 days. Daily fraction of radiotherapy were administered at 2.0 Gy on days 1 through 5. FHX cycles were repeated every 14 days until completion of radiotherapy. Total radiotherapy doses consisted of 70 Gy. Seventeen patients (mean age 56.53 years, range 40-73, male/female 15/2, site: oral cavity 6, 35.29%; oropharynx 3, 17.6%; hypopharynx 3, 17.65%; larynx 2, 11.76%; paranasal sinuses 2, 11.76%; salivary glands 1, 5.88%; ECOG PS 0/1: 10/7, stage: III/IV 3/14) were enrolled from January 1998 to August 1998. All 17 patients initiated induction chemotherapy on this protocol. Twelve patients were analyzed for response (5 patients were not evaluable): 2/12 (16.7%) patients achieved a CR and 10/12 (83.3%) achieved a PR for an ORR of 100%. Concomitant chemoradiotherapy was administered on protocol to 10 patients: 4 patients (40%) had CR, 3 patients (30%) had PR >/=70% for an ORR of 70%, 1 patient (10%) had SD and 2 patients (20%) had PD. As for local therapy, according to treatment plan, of the 8 eligible patients who completed chemoradiotherapy, the 4 patients with CR were submitted to random biopsies, which resulted histologically negative, the 3 patients with PR >/=70% underwent conservative organ-preserving surgery, the patient with SD underwent salvage surgery, preserving voice. Thus, organ-preservation was achieved in all 8 patients at the completion of all therapy: 4 patients had no surgical procedure and 3 patients only conservative surgery. Overall, after completion of all therapy, 6/8 (75%) patients were rendered disease-free. Both induction chemotherapy and concomitant chemoradiotherapy resulted in significant toxicity, which consisted mainly of mucositis and thrombocytopenia. In conclusion, in the present study we have achieved a good clinical response and an optimal organ preservation, at the cost of a severe toxicity.