Fichtner I, Lemm M, Becker M, Berthold F
Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
Anticancer Drugs. 1997 Feb;8(2):174-81. doi: 10.1097/00001813-199702000-00008.
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.
氨磷汀被开发用作一种放射和化学保护剂。在实验和临床研究中，它已显示出对全身辐射以及细胞毒性药物的骨髓和肾毒性具有保护作用。一些实验性试验揭示了在某些情况下氨磷汀对肿瘤生长或细胞毒性药物活性的影响。因此，我们工作的目的是在人异种移植神经母细胞瘤的临床前体内情况下评估氨磷汀的药理潜力。将人神经母细胞瘤细胞（IMR5 - 75和凯利细胞）皮下接种于裸鼠，使其生长至可触及大小（约4×5毫米）。然后给动物腹腔注射200毫克/千克氨磷汀，并在30分钟后用以下细胞毒性药物之一进行治疗：环磷酰胺、多柔比星、顺铂、异环磷酰胺、长春新碱和依托泊苷。仅使用氨磷汀治疗并未影响IMR5 - 75和凯利神经母细胞瘤的生长。我们未观察到该化合物本身的副作用。在任何情况下，氨磷汀与所联合使用的任何细胞抑制剂的抗肿瘤作用均未发生显著相互作用。然而，氨磷汀分别减轻了长春新碱诱导的体重减轻以及环磷酰胺、顺铂或异环磷酰胺诱导的白细胞减少。其余细胞抑制剂的副作用（如果观察到的话）未发生变化。我们得出结论，氨磷汀不影响异种移植神经母细胞瘤的肿瘤生长，也不降低所测试细胞抑制剂的抗肿瘤活性。有必要在临床环境中进一步研究氨磷汀作为化疗副作用保护剂的作用。
