Accelerated radiotherapy with carbogen and nicotinamide (ARCON) for laryngeal cancer

Background and purpose: Tumor hypoxia and tumor cell repopulation are known factors determining radiation response. Accelerated radiotherapy as a method to counteract cellular repopulation was combined with carbogen (95% O-2 + 5% CO2) breathing and oral administration of nicotinamide as a means to improve tumor perfusion and oxygenation. The feasibility, toxicity and clinical effectiveness of this approach as a voice-preserving treatment for carcinoma of the larynx was assessed in a prospective study. Patients and methods: Sixty-two patients with stage III-IV laryngeal carcinoma were treated with a schedule of accelerated radiotherapy. The total radiation dose to the primary tumor was 64 Gy and that to the metastatic nodes was 68 Gy delivered in fractions of 2 Gy over 35-37 days. Radiotherapy was combined with carbogen breathing in the initial 11 patients and with both carbogen and nicotinamide administration in the subsequent 51 patients. Results: After a median follow-up of 24 months, the actuarial local control rate at 2 years was 92%. This is higher than any previous report in the literature for this category of patients. Five patients had a local tumor recurrence and underwent laryngectomy. There was one regional recurrence. Including salvage surgery the loco-regional control rate was 100%. Four patients developed distant metastases and died. The actuarial overall survival rate at 2 years was 85%. Toxicity was increased relative to conventional radiotherapy but was considered as acceptable. One patient underwent laryngectomy for radiation-induced cartilage necrosis. Conclusion: These preliminary results indicate that advanced laryngeal cancer can be controlled in a high proportion of patients when treated with accelerated radiotherapy combined with carbogen and nicotinamide. This approach offers excellent possibilities for larynx preservation. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.