A phase III placebo-controlled study in advanced head and neck cancer using intratumoural cisplatin/epinephrine gel

Patients with recurrent or refractory head and neck squamous cell carcinoma received cisplatin/epinephrine injectable gel or placebo gel injected directly into the clinically dominant tumour. The double-blind phase III trial comprised of up to 6 weekly treatments over 8 weeks, 4 weekly evaluation visits, and then monthly follow-up; open-label dosing began as needed after three blinded treatments. Tumour response was defined as complete (100% regression) or partial (50–99% regression) sustained for ⩾28 day, and patient benefit as attainment of palliative or preventive goals prospectively selected by investigators and patients. With cisplatin/epinephrine gel, 25% (14 out of 57) of tumours responded (16% complete regression, 9% partial regression), vs 3% (one out of 35, complete regression) with placebo (P=0.007). Patient benefit was positively associated with target tumour response in the blinded period among cisplatin/epinephrine gel recipients (P=0.024): 43% (six out of 14) of responders benefited, vs 12% (five out of 43) of non-responders. The most frequent adverse event was pain during injection and the next most frequent was local cytotoxic effects consistent with the gel's mode of action. Systemic adverse events typical of intravenous cisplatin were uncommon. Intratumoural therapy with cisplatin/epinephrine gel provided safe, well-tolerated, effective palliative treatment for patients with locally advanced head and neck squamous cell carcinoma, who lack other satisfactory treatment options

Oral uracil-tegafur: an alternative to intravenous 5-fluorouracil?

The fluoropyrimidines have been used in the treatment of a number of tumour types over the past 40 years. Particular attention has focused on the use of 5-fluorouracil (5-FU) in colorectal cancer for which, until recently, there has been a lack of other effective chemotherapy. In an attempt to optimise the efficacy of fluoropyrimidines, a number of approaches have been used. These include alternative methods of iv. scheduling, the use of co-factors and the development of oral compounds. The aim of oral agents is to satisfy patient preference while maintaining the efficacy of sustained drug exposure seen with prolonged or continuous infusions of iv. 5-FU. One such oral compound is uracil-tegafur (UFT), which combines tegafur (ftorafur, a 5-FU prodrug) and uracil in a 1:4 molar ratio. UFT first entered Phase I trials in Japan over 20 years ago but has only recently received significant exposure in Phase II and III trials. Results from a number of Phase III studies in Europe and in the US are now becoming available. With UFT recently approved for colorectal cancer in many European countries, although not in the US, it is timely to review the current situation and future prospects for this agent