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 concomi tant chemoradiotherapy with the goal of organ-function preservation in adva nced head and neck cancer patients with the response rate and local control of disease as primary endpoints and the assessment of toxicity as secondar y endpoint. The overall treatment plan consisted of 3 cycles, each q. 28 da ys, of induction chemotherapy with cisplatin, 5-FU leucovorin and interfero n alpha 2b (PFL-IFN), followed by response evaluation and local therapy wit h concomitant chemoradiotherapy with 5-FU, hydroxyurea and concomitant radi otherapy (FHX). The evaluation of clinical response was performed during th e 2nd week after the 3rd cycle of induction chemotherapy and FHX was initia ted 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/m(2)/d for 5 days. Daily fraction of radiothe rapy were administered at 2.0 Gy on days 1 through 5. FHX cycles were repea ted every 14 days until completion of radiotherapy. Total radiotherapy dose s 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%; hypop harynx 3, 17.65%; larynx 2, 11.76%; paranasal sinuses 2, 11.76%; salivary g lands 1, 5.88%; ECOG PS 0/1: 10/7, stage: III/IV 3/14) were enrolled from J anuary 1998 to August 1998. All 17 patients initiated induction chemotherap y 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 adminis tered on protocol to 10 patients: 4 patients (40%) had CR, 3 patients (30%) had PR greater than or equal to 70% for an ORR of 70%, 1 patient (10%) had SD and 2 patients (20%) had PD. As for local therapy, according to treatme nt plan, of the 8 eligible patients who completed chemoradiotherapy, the 4 patients with CR were submitted to random biopsies, which resulted histolog ically negative, the 3 patients with PR greater than or equal to 70% underw ent conservative organ-preserving surgery, the patient with SD underwent sa lvage surgery, preserving voice. Thus, organ-preservation was achieved in a ll 8 patients at the completion of all therapy: 4 patients had no surgical procedure and 3 patients only conservative surgery. Overall, after completi on of all therapy, 6/8 (75%) patients were rendered disease-free. Both indu ction chemotherapy and concomitant chemoradiotherapy resulted in significan t toxicity, which consisted mainly of mucositis and thrombocytopenia. In co nclusion, in the present study we have achieved a good clinical response an d an optimal organ preservation, at the cost of a severe toxicity.