Combination chemotherapy for choroidal melanoma: ex vivo sensitivity to treosulfan with gemcitabine or cytosine arabinoside.
Combination chemotherapy for choroidal melanoma: ex vivo sensitivity to treosulfan with gemcitabine or cytosine arabinoside.
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DOI：
10.1038/sj.bjc.6690237
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发表时间：
1999-03
影响因子：
8.8
通讯作者：
Plowman, PN
中科院分区：
文献类型：
--
作者：
Neale, MH;Myatt, N;Cree, IA;Kurbacher, CM;Foss, AJE;Hungerford, JL;Plowman, PN
通过化学疗法治疗脉络膜黑色素瘤通常不成功，据报道，含达卡巴嗪 (DTIC) 的方案的反应率低于 1%，而对皮肤黑色素瘤的反应率为 20% 或更高。最近，我们报道了几种细胞毒性药物在基于 ATP 的肿瘤化学敏感性测定 (ATP-TCA) 中对抗原发性脉络膜黑色素瘤的活性。在这项研究中，我们使用相同的方法来检查脉络膜黑色素瘤对我们早期研究建议的组合的敏感性。对来自 36 个摘除眼睛的肿瘤材料进行了针对一系列单一药物和组合的测试，这些药物在之前的研究中显示出一些活性。三硫丹与吉西他滨或阿糖胞苷的组合分别在 70% 和 86% 的病例中显示出一致的活性。紫杉醇也具有活性，特别是与三硫丹（47%）或米托蒽醌（33%）联合使用时。在三硫丹+胞嘧啶类似物的组合中添加紫杉醇几乎没有增加敏感性。对于三硫丹+阿糖胞苷，进一步的序列和计时实验表明，同时给药产生最大的抑制作用，如果在三硫丹后24小时给予胞嘧啶类似物，则抑制作用轻微丧失。在三硫丹给药前 24 小时给予胞嘧啶类似物，在任何浓度下产生的抑制作用都显着降低。虽然我们迄今为止还无法研究脉络膜黑色素瘤患者的转移性肿瘤，但曲硫丹与吉西他滨或阿糖胞苷的组合显示出针对原发性肿瘤组织的离体活性。临床试验正在进行中。 © 1999 癌症研究运动
Treatment of choroidal melanoma by chemotherapy is usually unsuccessful, with response rates of less than 1% reported for dacarbazine (DTIC)-containing regimens which show 20% or more response rates in skin melanoma. Recently, we reported the activity of several cytotoxic agents against primary choroidal melanoma in an ATP-based tumour chemosensitivity assay (ATP-TCA). In this study, we have used the same method to examine the sensitivity of choroidal melanoma to combinations suggested by our earlier study. Tumour material from 36 enucleated eyes was tested against a battery of single agents and combinations which showed some activity in the previous study. The combination of treosulfan with gemcitabine or cytosine arabinoside showed consistent activity in 70% and 86% of cases, respectively. Paclitaxel was also active, particularly in combination with treosulfan (47%) or mitoxantrone (33%). Addition of paclitaxel to the combination of treosulfan + cytosine analogue added little increased sensitivity. For treosulfan + cytosine arabinoside, further sequence and timing experiments showed that simultaneous administration gave the greatest suppression, with minor loss of inhibition if the cytosine analogue was given 24 h after the treosulfan. Administration of cytosine analogue 24 h before treosulfan produced considerably less inhibition at any concentration. While we have so far been unable to study metastatic tumour from choroidal melanoma patients, the combination of treosulfan with gemcitabine or cytosine arabinoside shows activity ex vivo against primary tumour tissue. Clinical trials are in progress. © 1999 Cancer Research Campaign
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影响因子：
2.3
作者：
Kurbacher, CM;Cree, IA;Andreotti, PE
通讯作者：
Andreotti, PE
影响因子：
8.8
作者：
Foss, AJE;Dolin, PJ
通讯作者：
Dolin, PJ
影响因子：
2.3
作者：
Myatt, N;Cree, IA;Plowman, PN
通讯作者：
Plowman, PN
影响因子：
--
作者：
CANTORE, M;FIORENTINI, G;SMERIERI, F
通讯作者：
SMERIERI, F
影响因子：
8.4
作者：
Proebstle, TM;Scheibenbogen, C;Keilholz, U
通讯作者：
Keilholz, U