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 i n the last 2 weeks of radiation therapy in patients with previously untreat ed advanced squamous cell cancer of the head and neck region. Twenty-eight patients, all but two having UICC stage IV disease, were treat ed 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 da ys 1-5 of weeks 6 and 7 of a conventionally fractionated course of radiothe rapy. 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 complet e response rate of 71% (95% confidence interval (CI) 51-87%). The median fa ilure-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 y ears 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 fi rst or subsequent failure. The median overall survival of the whole group w as 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 co nfluent mucositis and 11 (39%) developed patchy mucositis. The median durat ion of mucositis for these 27 patients was 1.5 months. Seventeen patients ( 61%) required nutritional support for a median duration of 1.4 months. Four teen patients (50%) had grade three skin reactions, and 12 (43%) had one or more other significant (Grade 3) toxicities, predominantly infective. Grad e 3 late toxicity has been observed in three patients to date (three xerost omia, including one with severe depression), and one patient had chronic ul ceration of the oral tongue (grade 4). This chemoradiation regimen achieved an excellent complete response rate an d good locoregional control at 2 years in patients with a poor initial prog nosis. Acute toxicity was significant but manageable. The regimen offers an alternative to surgery and postoperative radiation therapy in locally adva nced head and neck cancer. (C) 2000 Elsevier Science Ireland Ltd. All right s reserved.