Dorr R T
Arizona Cancer Center, Tucson 85724.
Blood Rev. 1990 Mar;4(1):41-60. doi: 10.1016/0268-960x(90)90015-k.
The foregoing sections have reviewed the experimental studies and clinical anecdotes describing potential pharmacologic antidotes to extravasations of vesicant anticancer agents. Numerous prior reviews have also suggested specific antidotes or very conservative, non-pharmacologic approaches. Many antidotal approaches to extravasation have not been experimentally validated and thus, few 'antidotes' share a rationale which is founded on positive experimental and clinical studies. However, using this criteria, a few active antidotes can be distilled from the literature. These are outlined in Table 6. These antidotes include isotonic (1/6 M) sodium thiosulfate for mechlorethamine (and optionally for cisplatin), hyaluronidase for the vinca alkaloids (and optionally for epipodophyllotoxins such as etoposide), and cooling with very topical DMSO and low dose hydrocortisone for the anthracyclines. For the alkylating agent mitomycin C, topical DMSO has been effective experimentally but has not yet received clinical validation, at least in published studies. Nonetheless, the severity of mitomycin C ulcerations and the documented safety of topical DMSO in the small series of doxorubicin extravasation patients argues for its use when mitomycin extravasates in the clinic. Furthermore, except for DMSO, all of these extravasation antidotes are listed in the official FDA-approved package inserts for each vesicant agent. Thus, the inserts for vincristine and vinblastine specify hyaluronidase, for doxorubicin, glucocorticosteroids, and for mechlorethamine, sodium thiosulfate. New studies are clearly needed to clarify the role of topical DMSO with anthracyclines and mitomycin C. In addition, efforts should be made to begin clinical development of radical dimers such as DHM3 which can directly inactivate quinone-containing vesicants like doxorubicin and mitomycin C. Although the incidence of chemotherapy extravasation may be lessened with vascular access devices, it nonetheless, continues to comprise a serious and highly litigious area of oncology practice. This commands continued extravasation intervention studies and diligent prevention when ever possible.
上述各节回顾了描述针对刺激性抗癌药物外渗的潜在药理学解毒剂的实验研究和临床轶事。许多先前的综述也提出了具体的解毒剂或非常保守的非药理学方法。许多外渗解毒方法尚未经过实验验证，因此，很少有“解毒剂”具有基于积极实验和临床研究的理论依据。然而，按照这一标准，可以从文献中提炼出一些有效的解毒剂。这些总结在表6中。这些解毒剂包括用于氮芥（也可用于顺铂）的等渗（1/6M）硫代硫酸钠、用于长春花生物碱（也可用于依托泊苷等表鬼臼毒素）的透明质酸酶，以及用于蒽环类药物的局部使用二甲基亚砜（DMSO）和低剂量氢化可的松进行冷敷。对于烷化剂丝裂霉素C，局部使用DMSO在实验中有效，但至少在已发表的研究中尚未得到临床验证。尽管如此，丝裂霉素C溃疡的严重性以及在小系列多柔比星外渗患者中记录的局部使用DMSO的安全性，支持在临床中丝裂霉素外渗时使用它。此外，除了DMSO之外，所有这些外渗解毒剂都列在FDA官方批准的每种刺激性药物的包装说明书中。因此，长春新碱和长春碱的说明书中指定了透明质酸酶，多柔比星的说明书中指定了糖皮质激素，氮芥的说明书中指定了硫代硫酸钠。显然需要新的研究来阐明局部使用DMSO对蒽环类药物和丝裂霉素C的作用。此外，应该努力开始对像DHM3这样的自由基二聚体进行临床开发，其可以直接使含醌的刺激性药物如多柔比星和丝裂霉素C失活。尽管使用血管通路装置可能会降低化疗外渗的发生率，但它仍然是肿瘤学实践中一个严重且极易引发诉讼的领域。这就要求持续进行外渗干预研究，并尽可能地进行勤勉预防。
