Lewis C
Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia.
Drug Saf. 1994 Sep;11(3):153-62. doi: 10.2165/00002018-199411030-00002.
Dose-limiting toxicity secondary to antineoplastic chemotherapy is principally due to the inability of the drugs to differentiate between normal and malignant cells. This results in normal tissue damage, as well as the desired antitumour effect. Toxicity may be acute, as in cisplatin-induced nephrotoxicity or alkylating agent myelotoxicity and haemorrhagic cystitis, or cumulative, as in anthracycline-related cardiac toxicity or cisplatin neurotoxicity. The consequences of this often include serious adverse effects and the inability to deliver adequate dose-intensive therapy against the cancer. Chemoprotective agents have been developed to provide site-specific protection against normal tissue toxicity, without compromising antitumour activity. Several chemoprotective compounds have recently been developed, including dexrazoxane (ICRF-187), amifostine (ethiofos: WR-2721), mesna and ORG-2766. Initial results confirm their promise as selective protective agents, although further randomised trials are required to identify their optimal role when used alone or in combination with other toxicity modifiers, including haematopoietic growth factors, with the ultimate aim being adequate dose escalation of chemotherapy to overcome tumour resistance.
抗肿瘤化疗继发的剂量限制性毒性主要是由于药物无法区分正常细胞和恶性细胞。这导致了正常组织损伤以及预期的抗肿瘤效果。毒性可能是急性的，如顺铂诱导的肾毒性、烷化剂骨髓毒性和出血性膀胱炎，也可能是累积性的，如蒽环类药物相关的心脏毒性或顺铂神经毒性。其后果通常包括严重的不良反应以及无法提供足够的剂量密集型抗癌治疗。已经开发出化学保护剂，以针对正常组织毒性提供位点特异性保护，同时不影响抗肿瘤活性。最近开发了几种化学保护化合物，包括右丙亚胺（ICRF-187）、氨磷汀（乙磺磷：WR-2721）、美司钠和ORG-2766。初步结果证实了它们作为选择性保护剂的前景，不过还需要进一步的随机试验来确定它们单独使用或与其他毒性调节剂（包括造血生长因子）联合使用时的最佳作用，最终目标是充分提高化疗剂量以克服肿瘤耐药性。
