Effects of amifostine (WR-2721, ethyol) on tumor growth and pharmacology of cytotoxic drugs in human xenotransplanted neuroblastomas.

Amifostine was developed as a radio- and chemoprotective agent. It has shown protection against whole-body irradiation, and myelo- and nephrotoxicity of cytotoxic agents both in experimental and clinical studies. Some experimental trials revealed an influence of amifostine on tumor growth or the activity of cytotoxic drugs under certain circumstances. Therefore, it was the aim of our work to evaluate the pharmacological potential of amifostine in a preclinical in vivo situation with human xenotransplanted neuroblastomas. Human neuroblastoma cells (IMR5-75 and Kelly) were grown s.c. as xenografts in nude mice to palpable sizes (approximately 4 x 5 mm). Then the animals received 200 mg/kg amifostine i.p. and were treated 30 min later with one of the following cytotoxic drugs: cyclophosphamide, doxorubicin, cisplatin, ifosfamide, vincristine and etoposide. Amifostine as the only treatment did not influence the growth of the neuroblastomas IMR5-75 and Kelly. We observed no side effects of the compound itself. In no case did amifostine interact significantly with the antitumor effect of any cytostatic used in combination. However, amifostine mitigated the body weight loss induced by vicristine and the leukopenia induced by cyclophosphamide, cisplatin or ifosfamide, respectively. The side effects of the remaining cytostatics were--if observed at all--unchanged. We conclude that amifostine did not influence the tumor growth of xenotransplanted neuroblastomas and did not reduce the antineoplastic activity of the tested cytostatic drugs. Further investigation of amifostine as a protectant from side effects of chemotherapy in a clinical setting is warranted.