Amifostine does not alter the antitumor activity of cisplatin in a pre-clinical model of testicular cancer

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Abstract

Testicular germ cell tumors are so exquisitely sensitive to cisplatin that the majority of patients with this cancer are now cured with modern platinum-based chemotherapy. In contrast to some other tumor types, testicular germ cell tumors are known to express alkaline phosphatases (ALP). Amifostine is an aminothiol pro-drug which is rapidly dephosphorylated by ALP at the cell surface of healthy tissues and which exerts a clinically proven protective effect against chemotherapy associated toxicity. The aim of this pre-clinical study was to assess the potential of amifostine to protect platinum-sensitive non-seminomatous germ cell tumor (NSGCT) nude mouse xenografts established from an ALP-positive embryonal carcinoma (EC) cell line, from the cytotoxicity of cisplatin when both were administered at their individual maximally tolerated doses (MTD). The %T/C values calculated at day 30 for nude mice carrying H12.1 NSGCT xenografts treated with amifostine alone, amifostine plus cisplatin or cisplatin alone were, respectively, 93, 3 or 3%. Mean tumor volumes were not significantly different between mice treated with the combination versus cisplatin alone at day 14 or 30. The results of this study revealed no evidence of tumor protection by amifostine, confirming previous results in other tumor types.

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