Phase II study of temozolomide and thalidomide in patients with metastatic melanoma in the brain: high rate of thromboembolic events (CALGB 500102).
Phase II study of temozolomide and thalidomide in patients with metastatic melanoma in the brain: high rate of thromboembolic events (CALGB 500102).
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替莫唑胺和沙利度胺治疗脑转移性黑色素瘤患者的 II 期研究：血栓栓塞事件发生率高 (CALGB 500102)。
DOI：
10.1002/cncr.22239
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发表时间：
2006
期刊：
影响因子：
6.2
通讯作者：
CancerandLeukemiaGroupB
中科院分区：
文献类型：
--
作者：
Krown,SusanE;Niedzwiecki,Donna;Hwu,Wen-Jen;Hodgson,Lydia;Houghton,AlanN;Haluska,FrankG;CancerandLeukemiaGroupB
背景初步研究表明，延长剂量的替莫唑胺联合沙利度胺对转移性黑色素瘤患者是安全且有效的，因此经常使用这种口服疗法。为了证实这些观察结果，该组合在黑色素瘤脑转移患者的多中心 II 期试验中进行了测试。方法符合条件的患者患有黑色素瘤脑转移，伴或不伴全身转移。主要终点是脑转移的缓解率。患者接受替莫唑胺治疗，剂量为 75 mg/m2/天，持续 6 周，周期之间休息 2 周，并接受沙利度胺（对于年龄 <70 岁的患者，剂量增加至 400 mg/天；对于年龄 ≥ 70 岁的患者，剂量增加至 200 mg/天）。 2 阶段设计要求前 21 名患者获得 ≥3 次缓解，然后再在第二阶段招募 29 名额外患者。 结果 16 名符合条件的患者被招募。没有观察到客观反应。中位生存期为 23.9 周。 7名患者因肿瘤进展而退出； 7例在第1周期因不良事件被移除，包括过敏反应（1例患者）、严重疲劳（1例患者）、猝死（1例患者）和血栓栓塞事件（3例患者肺栓塞和1例患者深静脉血栓）；当研究暂停并随后结束时，2 名患者退出。基线特征和毒性之间无法建立关联。 结论 发生致命或可能危及生命的不良事件的患者比例很高（0.31，95%置信区间，0.11-0.59），并且缺乏客观反应使得进一步的累积不太可能证明该方案的有效性。除非开发出安全有效的方法来预防血栓形成，否则这些观察结果对使用这种组合治疗黑色素瘤脑转移几乎没有提供支持。癌症 2006。© 2006 美国癌症协会。
BACKGROUNDPreliminary studies suggesting that extended‐dose temozolomide with thalidomide is safe and active in patients with metastatic melanoma have led to frequent use of this oral regimen. To confirm these observations the combination was tested in a multicenter Phase II trial in patients with melanoma brain metastases.METHODSEligible patients had melanoma brain metastases, with or without systemic metastases. The primary endpoint was response rate in brain metastases. Patients received temozolomide at a dose of 75 mg/m2/day for 6 weeks with a 2‐week rest between cycles, and thalidomide (escalated to 400 mg/day for patients age <70 years or to 200 mg/day for patients age ≥70 years). A 2‐stage design required ≥3 responses in the first 21 patients before enrolling 29 additional patients in the second stage.RESULTSSixteen eligible patients were enrolled. No objective responses were observed. The median survival was 23.9 weeks. Seven patients withdrew because of tumor progression; 7 were removed during Cycle 1 because of adverse events, including allergic reaction (1 patient), severe fatigue (1 patient), sudden death (1 patient), and thromboembolic events (pulmonary embolism in 3 patients and deep vein thrombosis in 1 patient); 2 patients withdrew when the study was suspended and subsequently closed. No associations could be established between baseline characteristics and toxicity.CONCLUSIONSThe proportion of patients with lethal or potentially life‐threatening adverse events was high (0.31, 95% confidence interval, 0.11–0.59), and the absence of objective responses made it unlikely that further accrual would demonstrate the efficacy of the regimen. These observations provide little support for the use of this combination for melanoma brain metastases unless safe and effective methods to prevent thrombosis are developed. Cancer 2006. © 2006 American Cancer Society.