Randomized study of a short course of weekly cisplatin with or without amifostine in advanced head and neck cancer

Background: Cisplatin is one of the most active cytotoxic agents available for the treatment of patients with head and neck cancer. In a previous phas e II study with weekly administration of cisplatin, a response rate of 51% was achieved. However, only in a minority of the patients the planned high dose intensity of 80 mg/m(2)/week could be reached because of toxicity, mai nly thrombocytopenia and ototoxicity. Amifostine is a cytoprotective drug t hat can diminish the toxicity of alkylating agents and platinum compounds. Therefore the effect of amifostine on toxicity and activity of weekly cispl atin was investigated in a randomized study. Patients and methods: Patients with locally advanced, recurrent or metastat ic head and neck cancer were eligible. Patients were randomized to weekly c isplatin 70 mg/m(2) for six cycles preceded by amifostine 740 mg/m(2), or c isplatin only. Cisplatin was administered in hypertonic saline (3% NaCl) as a one-hour infusion; amifostine was administered as a 15-minute infusion d irectly before the administration of cisplatin. Results: Seventy-four patients were entered in the study. The median number of cisplatin administrations was 6 (range 2-6), equal in both arms. In bot h treatment arms the median dose intensity of cisplatin achieved was the pl anned 70 mg/m(2)/week. In the cisplatin only arm 6 out of 206 cycles were c omplicated by thrombocytopenia grade 3 or 4 versus 1 of 184 cycles in the a mifostine arm (P = 0.035). Hypomagnesaemia grade 2 + 3 was significantly le ss observed in the amifostine arm (P = 0.04). Neurotoxicity analyzed by ser ial vibration perception thresholds (VPT) showed a diminished incidence of subclinical neurotoxicity in the amifostine arm (P = 0.03). No protective e ffect on renal and ototoxicity could be shown. Hypotension was the main sid e effect of amifostine but only of relevance in one patient. The antitumor activity of cisplatin was preserved as 63% of the evaluable patients in the amifostine arm responded compared to 50% of the evaluable patients in the cisplatin alone arm. Conclusion: Our study indicated that in combination with weekly administere d cisplatin amifostine reduced the risk of thrombocytopenia, hypomagnesemia as well as subclinical neurotoxicity, but did not result in a higher dose intensity of cisplatin. Addition of amifostine did not compromise the antit umor effect of cisplatin.