Schedule-dependent therapeutic efficacy of the combination of gemcitabine and cisplatin in head and neck cancer xenografts

Gemcitabine and cisplatin are both drugs with proven clinical activity in various tumour types, have no overlapping toxic side-effects and are different with respect to cellular metabolism. We, therefore, performed an in vivo study to determine the efficacy of the combination of these two drugs using two human head and neck squamous cell carcinoma xenograft lines, subcutaneously growing in athymic nude mice. 100 mg/kg gemcitabine was given intraperitoneally on days 0, 3, 6 and 9 and 4 mg/kg cisplatin intravenously on days 0 and 6. In one tumour line, the combination treatment resulted in better effects than those observed when the drugs were administered individually. In the other cell line, addition of cisplatin did not increase the moderate effect of gemcitabine. Experiments with single dose injections of both drugs showed adverse effects when the interval was extended to 24 h. These data are of potential interest for clinical application, and suggest that the drugs should be administered either simultaneously or with a short time interval in which cisplatin should precede gemcitabine.