The ex vivo chemosensitivity profile of choroidal melanoma
The ex vivo chemosensitivity profile of choroidal melanoma
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DOI：
10.1097/00001813-199709000-00004
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发表时间：
1997-09-01
影响因子：
2.3
通讯作者：
Plowman, PN
中科院分区：
文献类型：
--
作者：
Myatt, N;Cree, IA;Plowman, PN
葡萄膜黑色素瘤有很高的死亡率，对现有的化疗反应很差。因此，我们已经检查了葡萄膜黑色素瘤细胞毒性药物的敏感性，使用离体化疗敏感性测定，以确定是否有一些尚未用于这种肿瘤的药物可能具有活性。应用ATP-TCA肿瘤药敏试验（ATP-TCA），对28例原发性葡萄膜黑色素瘤标本进行了9种细胞毒药物多稀释度的疗效测定。（丝裂霉素C组9例中的3例，顺铂组15例中的1例，曲舒凡组15例中的7例），阿糖胞苷组（16例中的7例），紫杉醇组（5例中的1例）和阿霉素组（16例中的2例）。没有肿瘤对替莫唑胺或5-氟尿嘧啶敏感，14个肿瘤中只有1个对长春新碱敏感。在测试的五种肿瘤中，曲舒凡与阿糖胞苷的组合导致了三种肿瘤细胞抑制作用的增强。含有紫杉醇与阿霉素或顺铂的组合显示出一定的活性，但没有达到100%的抑制，并且结果与紫杉醇单独使用获得的结果相似。葡萄膜黑色素瘤显示出对细胞毒性药物的敏感性的相当大的异质性，对大多数药物具有相当大的耐药性，与临床经验相匹配。结果表明，阿糖胞苷或吉西他滨加曲舒凡可能是一个积极的组合。临床试验将很快开始。AIP-TCA的使用提供了一种测试多种药物和组合的方法，这种方法在罕见肿瘤如葡萄膜黑色素瘤中是不可能的。
Uveal melanoma has a high mortality rate and responds poorly to existing chemotherapy. We have therefore examined the sensitivity of uveal melanoma to cytotoxic agents using an ex vivo chemosensitivity assay to determine whether some agents which have not been used for this tumor might have activity. An ATP-based tumor chemosensitivity assay (ATP-TCA) was used to determine the effect of nine cytotoxic drugs at multiple dilutions in 28 primary uveal melanoma specimens, Evaluable assay results from up to 16 tumors with each drug showed variable sensitivity to alkylating agents (three of nine with mitomycin C, one of 15 with cisplatin and seven of 15 with treosulfan), cytosine arabinoside (seven of 16), paclitaxel (one of five) and doxorubicin (two of 16). No tumors were sensitive to temozolomide, or 5-fluorouracil, and only one of 14 to vincristine. The combination of treosulfan with cytosine arabinoside resulted in enhanced tumor cell inhibition in three of five tumors tested. Combinations containing paclitaxel combined with doxorubicin or cisplatin showed some activity, but none achieved 100% inhibition and the results were similar to those obtained with paclitaxel alone, Uveal melanoma shows considerable heterogeneity of sensitivity to cytotoxic drugs, with considerable resistance to most agents, matching clinical experience. The results suggest that cytosine arabinoside or gemcitabine plus treosulfan may be an active combination. Clinical trials will commence shortly. The use of the AIP-TCA provides a method of testing multiple agents and combinations in a way which would be otherwise impossible in rare tumors such as uveal melanoma.