Radiation with concurrent late chemotherapy intensification ('chemoboost') for locally advanced head and neck cancer

The aim of this study was to review our experience with a treatment regimen that combined conventionally fractionated radiation therapy (70 Gy over 7 weeks) with chemotherapy (cisplatin and fluorouracil), given concurrently in the last 2 weeks of radiation therapy in patients with previously untreated advanced squamous cell cancer of the head and neck region. Twenty-eight patients, all but two having UICC stage IV disease, were treated at the Peter MacCallum Cancer Institute between November 1995 and April 1998. Planned chemotherapy consisted initially of continuous infusion at 10 mg/m(2) per day of cisplatin and 400 mg/m(2) per day of fluorouracil on days 1-5 of weeks 6 and 7 of a conventionally fractionated course of radiotherapy. After the first 14 patients, the dose of fluorouracil was reduced to 360 mg/m(2) per day because of acute toxicity. Twenty patients had a complete response to chemoradiation, giving a complete response rate of 71% (95% confidence interval (CI) 51-87%). The median failure-free survival was estimated to be 12.3 months (CI, 5.8- > 35.2 months). The estimated cumulative incidences of the sites of first failure at 2 years were 41% (CI, 22-60%) for locoregional relapse (or persistent disease) and 16% (CI, 2-30%) for distant metastases. Altogether an estimated 25% of patients (CI, 7-43%) developed distant metastases by 2 years, either as first or subsequent failure. The median overall survival of the whole group was estimated to be 23.5 months (CI, 16.5- > 36.8 months), with an estimated 50% surviving at 2 years (CI, 29-71%). Sixteen patients (57%) developed confluent mucositis and 11 (39%) developed patchy mucositis. The median duration of mucositis for these 27 patients was 1.5 months. Seventeen patients (61%) required nutritional support for a median duration of 1.4 months. Fourteen patients (50%) had grade three skin reactions, and 12 (43%) had one or more other significant (Grade 3) toxicities, predominantly infective. Grade 3 late toxicity has been observed in three patients to date (three xerostomia, including one with severe depression), and one patient had chronic ulceration of the oral tongue (grade 4). This chemoradiation regimen achieved an excellent complete response rate and good locoregional control at 2 years in patients with a poor initial prognosis. Acute toxicity was significant but manageable. The regimen offers an alternative to surgery and postoperative radiation therapy in locally advanced head and neck cancer. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.