Phase II study of induction chemotherapy followed by concomitant chemoradiotherapy in advanced head and neck cancer: Clinical outcome, toxicity and organ/function preservation

The purpose of the study was to assess response rate, clinical outcome, org an/function preservation and toxicity in head and neck cancer patients trea ted with induction chemotherapy followed by concomitant chemoradiotherapy a nd, when necessary, limited surgery. The study design was a phase II nonran domized trial in hospitalized patients setting. The treatment plan consiste d of 3 cycles of induction chemotherapy with cisplatin, fluorouracil (5-FU) , leucovorin and interferon alpha 2b (PFL-IFN) followed by 7 cycles of 5-FU , hydroxyurea and concomitant radiation for 5 days (FHX) for a total radiat ion dose of 70 Gy. Surgical resection was performed, when necessary, with t he intent to spare organ/function. Seventeen patients were treated at one i nstitution. Three patients had stage III and 14 patients stage IV disease. Twelve patients were analyzed for response to PFL-IFN: 2/12 (16.7%) patient s achieved a CR and 10/12 (83.3%) achieved a PR for an ORR of 100%. FHX was administered on protocol to 10 patients: 4 patients (40%) had CR, 3 (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, of the 8 eligible pat ients who completed chemoradiotherapy, the 3 patients with CR were submitte d to random biopsies, results of which were histologically negative, 3 pati ents with PR greater than or equal to 70% underwent conservative organ-pres erving surgery, and 1 patient with PR >70% refused surgery, whereas the pat ient with SD underwent salvage surgery, preserving voice. Thus, organ prese rvation was achieved in all 8 patients at the completion of all therapy: 4 patients had no surgical procedure and 4 patients only conservative surgery . Overall, after completion of all therapy, 5/8 (62.5%) patients were rende red disease-free. The median overall survival time was 23 months, the media n duration of response was 6 months and the median time to progression was 9 months. Both induction chemotherapy and concomitant chemoradiotherapy res ulted in significant toxicity, which consisted mainly of mucositis and thro mbocytopenia. In conclusion, PFL-IFN was very active, producing high ORRs a nd, followed by FHX, resulted in high overall survival rates permitting an optimal organ preservation, at the cost of a severe toxicity.