Neurotoxicity in a phase I trial of continuous-infusion cisplatin with hyperfractionated radiotherapy for locally advanced head and neck cancer

Background. Both twice daily fractionated radiotherapy and concurrent cisplatin with once-daily radiotherapy have been shown to improve local disease control in patients with head and neck cancer. The objective of this phase I trial was to determine the maximum tolerated dose of cisplatin which could be given as a continuous infusion concurrent with twice-daily radiotherapy to patients with locally advanced head and neck cancer. Methods. Patients were treated with radiotherapy at doses of 110 cGy twice daily for 5 days per week to a total dose of 7040-7590 cGy. Concurrent with radiotherapy, patients received continuous-infusion cisplatin for 5 days per week. Groups of 3-6 patients were treated with doses of 1-3 mg/m(2)/day. Results. Central nervous system toxicity became dose-limiting. At 1 mg/m(2), 2 mg/m(2), and 3 mg/m(2) confusion was observed and one patient had a seizure. At 3 mg/m(2), another patient suffered severe sensory and motor neuropathy. Despite bulky tumors, 12 of the 14 patients had an objective response and 3 achieved a complete response. Conclusions. The combination of twice-daily fractionated radiotherapy and concurrent cisplatin by continuous infusion is severely toxic and achieves results similar to less toxic programs. It is not recommended for further investigation or therapy.