Does chemotherapy have a role in the management of patients with advanced head and neck cancer? Early Results from the UK Head and Neck (UKHAN) Trial

The role of chemotherapy in advanced squamous cell carcinoma of the head and neck remains controversial. Radical radiotherapy alone, or following neoadjuvant (induction) or given simultaneously with chemotherapy has been subjected to trials but no reliable conclusions reached. The UKHAN trial was designed in 1990 to evaluate the effect of adding chemotherapy (CT) to standard radical treatment with radiotherapy (RT) alone or surgical excision followed by RT in the treatment of advanced head and neck cancer. It was recognised from the outset that the trial needed to recruit large numbers of patients - 1,000 patients for 90% power. Consultation in the UK led to the conclusion that chemotherapy needed to be given on an outpatient basis. Eligible patients had advanced squamous cell carcinoma of the head and neck (stage II û IV) but no evidence of distant metastases and were fit to receive any of the treatments. After giving consent patients were randomised to one of four arms: [1] RT alone. [2] RT with 2 courses of simultaneous CT administered days 1 & 14 of RT (SIM CT). [3] RT with 2 courses of subsequent CT administered 14 & 28 days after completion of RT (SUB CT). [4] RT with both SIM CT and SUB CT (4 courses). Patients referred following surgery were randomised only to arms [1] & [2]. Centres chose either single agent methotrexate or combination VBMF (vincristine, bleomycin, methotrexate and 5-fluorouracil). Between January 1990 and study closure in July 2000 971 patients were entered. The current analysis included the first 947 patients who had been followed for at least six months (median follow-up was 3.5 years). Patients randomised to SIM CT demonstrated increased complete clinical responses, six months from randomisation, (73% vs 69% non-significant) and improved event-free survival (RR = 0.77, 95% CI 0.64-0.93, p<0.02). No advantage has been shown for patients randomised to SUB CT. Overall survival was not shown to differ between the groups. These results confirm those from the meta-analyses which demonstrated that synchronous chemoradiation improves outcome for patients with squamous head and neck cancer.