Bedikian Agop Y, Papadopoulos Nicholas, Plager Carl, Eton Omar, Ring Sigrid
The University of Texas M.D. Anderson Cancer Center, Department of Melanoma Medical Oncology, Houston, Texas 77030, USA.
Melanoma Res. 2003 Jun;13(3):303-6. doi: 10.1097/00008390-200306000-00013.
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/m2 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.
替莫唑胺（泰道）已显示出对黑色素瘤的临床活性与静脉注射达卡巴嗪（氮烯咪胺）相当。I期临床研究表明，低剂量长期给予替莫唑胺比5天给药方案能实现更高的剂量强度。替莫唑胺从胃肠道吸收后会水解为其活性代谢物单甲基三嗪咪唑甲酰胺（MTIC），而达卡巴嗪在肝脏代谢为MTIC之前是无活性的。鉴于此，当MTIC的来源是替莫唑胺而非达卡巴嗪时，更高浓度的MTIC在首过效应期间会通过肝脏。为了确定替莫唑胺的这些特性是否会转化为比达卡巴嗪更高的缓解率，我们对转移性至肝脏的葡萄膜黑色素瘤患者进行了替莫唑胺的II期临床试验。替莫唑胺口服给药，起始剂量为每天75mg/m²，每4周给药21天。14名患者入组该试验。未观察到完全或部分缓解。2名患者病情稳定。治疗耐受性良好。我们得出结论，与达卡巴嗪一样，本试验中所研究剂量和给药方案的替莫唑胺对控制葡萄膜源性转移性黑色素瘤无效。
