We compared concurrent combination chemotherapy and radiotherapy with surgery and adjuvant radiotherapy in patients with stage III/IV nonmetastatic squamous cell head and neck cancer. Patients with non-nasopharyngeal and nonsalivary resectable squamous cell head and neck cancer were randomised to receive either surgery followed by adjuvant radiotherapy (60 Gy over 30 fractions) or concurrent combination chemotherapy and radiotherapy (66 Gy in 33 fractions). Combination chemotherapy comprised two cycles of i.v. cisplatin 20 mg m À2 day À1 and i.v. 5-fluorouracil 1000 mg m À2 day À1 , both to run over 96 h given on days 1 and 28 of the radiotherapy. A total of 119 patients were randomised. At a median follow-up of 6 years, there was no significant difference in the 3-year disease-free survival rate between the surgery and concurrent chemoradiotherapy (50 vs 40% respectively). The overall organ preservation rate or avoidance of surgery to primary site was 45%. Those with laryngeal/hypopharyngeal disease subsite had a higher organ-preservation rate than the rest (68 vs 30%). Combination chemotherapy and concurrent irradiation with salvage surgery was not superior to conventional surgery and postoperative radiotherapy for resectable advanced squamous cell head and neck cancer. However, this form of treatment schedule with a view to organ-preservation can be attempted especially for those with laryngeal/hypopharyngeal and possibly oropharyngeal disease subsites. The majority of the patients with squamous cell head and neck cancer (SCHNC) present with locally and/or regionally advanced disease and the use of radical surgery and/or radiotherapy in this setting yield low locoregional control rates and 5-year survival rates not exceeding 40%.The administration of chemotherapy and radiotherapy concurrently makes use of the resultant synergistic activity to improve tumour cell kill. This strategy has found success in anal canal carcinoma, allowing high cure rates while obviating the need for radical surgery. Studies carried out in the 1990s using combination chemotherapy with concurrent radiation in SCHNC have shown this treatment approach to be feasible despite the significantly higher toxicity and have produced encouraging results. Adelstein et al in a phase II trial using cisplatin (CDDP) and 5-fluorouracil (5FU) combination with concurrent split-course radiotherapy have reported a 4-year relapse-free survival of 45% and an overall survival of 49% (Adelstein et al, 1993). This when compared retrospectively with a similar patient population treated with radiation alone was shown to be improved. Adelstein next investigated the use of the same combination regimen concurrently with a continuous course of radiotherapy (Adelstein et al, 1994). In 19 patients treated in this fashion, despite significant toxicity, there were no treatment-related deaths. At a median follow-up of 20 months, the projected Kaplan -Meier estimate of locoregional disease control was 92%, with the projected relapse-free survival of 86%. Of significance...

The Simon two-stage minimax design is a popular statistical design used in Phase II clinical trials. The analysis of the data arising from the design typically involves the use of frequentist statistics. This paper presents an alternative, Bayesian, approach to the design and analysis of Phase II clinical trials. In particular, we consider how a Bayesian approach could have affected the design, analysis and interpretation of two parallel Phase II trials of the National Cancer Centre Singapore, on the activity of gemcitabine in chemotherapy-naïve and in previously treated patients with metastatic nasopharyngeal carcinoma. We begin by explaining the Bayesian methodology and contrasting it with the frequentist approach. We then carry out a Bayesian analysis of the trial results. The conclusions drawn using the Bayesian approach were in general agreement with those obtained from the frequentist analysis. However they had the advantage of allowing for different and potentially more useful interpretations to be made regarding the trial results, as well as for the incorporation of external sources of information. In particular, using a Bayesian trial design, we were able to take into account the results of the parallel trial results when deciding whether to continue each trial beyond the interim stage.

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