Phase II evaluation of temozolomide in metastatic choroidal melanoma
Phase II evaluation of temozolomide in metastatic choroidal melanoma
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DOI：
10.1097/00008390-200306000-00013
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发表时间：
2003-06-01
影响因子：
2.2
通讯作者：
Ring, S
中科院分区：
文献类型：
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作者：
Bedikian, AY;Papadopoulos, N;Ring, S
替莫唑胺（Temodar）已证明对黑色素瘤的临床活性与静脉注射达卡巴嗪（DTIC）相当。I期临床研究表明，替莫唑胺的低剂量长期给药允许递送比5天剂量方案更高的剂量强度。替莫唑胺在胃肠道吸收后水解为其活性代谢物单甲基三氮烯咪唑甲酰胺（MTIC），而DTIC在肝脏中代谢为MTIC之前无活性。鉴于此，当其来源是替莫唑胺而不是DTIC时，较高浓度的MTIC将在第一次通过期间通过肝脏。为了确定替莫唑胺的这些特征是否会转化为比DTIC更高的反应率，我们在葡萄膜黑色素瘤转移到肝脏的患者中进行了替莫唑胺的II期临床试验。替莫唑胺口服给药，起始剂量为75 mg/m2/天，每4周一次，持续21天。14例患者入组试验。未观察到完全或部分缓解。2例患者病情稳定。治疗耐受性良好。我们的结论是，像DTIC，替莫唑胺在本试验中研究的剂量和时间表是无效的葡萄膜起源的转移性黑色素瘤的控制。
Temozolomide (Temodar) has demonstrated clinical activity against melanoma equivalent to that of intravenous dacarbazine (DTIC). Phase I clinical studies have shown that low dose chronic administration of temozolomide permits the delivery of higher dose intensities than a 5 day dose schedule. Temozolomide is hydrolysed to its active metabolite monomethyltriazenoimidazole carboxamide (MTIC) upon absorption from the gastrointestinal tract, while DTIC is inactive until it is metabolized in the liver to MTIC. In view of this, a higher concentration of MTIC will pass through the liver during the first pass when its source is temozolomide rather than DTIC. To determine if these characteristics of temozolomide will translate into a higher response rate than that achieved with DTIC, we conducted a phase II clinical trial of temozolomide in patients with uveal melanoma metastatic to the liver. Temozolomide was administered orally at a starting dose of 75 mg/m(2) per day for 21 days every 4 weeks. Fourteen patients were enrolled in the trial. No complete or partial responses were observed. Stabilization of disease was achieved in two patients. The treatments were well tolerated. We conclude that, like DTIC, temozolomide at the dose and schedule studied in this trial is not effective for the control of metastatic melanoma of uveal origin.