Temozolomide for the treatment of brain metastases associated with metastatic melanoma: A phase II study
Temozolomide for the treatment of brain metastases associated with metastatic melanoma: A phase II study
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DOI：
10.1200/jco.2004.11.044
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发表时间：
2004-06-01
影响因子：
45.3
通讯作者：
Rankin, EM
中科院分区：
文献类型：
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作者：
Agarwala, SS;Kirkwood, JM;Rankin, EM
目的.替莫唑胺是一种耐受性良好的口服烷化剂，在CNS中具有活性。进行了一项多中心、开放标签、II期研究，以评估替莫唑胺在不需要立即放疗的转移性黑色素瘤（MM）脑转移患者中的安全性和疗效。患者和方法。符合条件的患者经组织学证实患有MM至脑部，且既往未接受过针对脑转移瘤的放疗或放射外科手术。既往未接受治疗的患者接受替莫唑胺200 mg/m2/d × 5天，既往接受治疗的患者接受150 mg/m2/d × 5天，每28天一次。治疗持续1年或直至疾病进展或不可接受的毒性。在151例入组患者中，117例既往未接受过全身化疗，34例既往接受过MM化疗。在既往未接受过治疗的患者中，25%的患者有4处以上脑病变，8例（7%）达到客观缓解（1例完全缓解，7例部分缓解），34例（29%）脑转移瘤病情稳定。中位总生存期为3.5个月。在既往接受过治疗的患者中，21%的患者有4个以上的脑病变，1个有部分缓解，6个（18%）脑转移瘤病情稳定。中位总生存期为2.2个月，替莫唑胺耐受性良好，4例（3%）患者因不良事件停药。3/4级血液学毒性包括血小板减少（3%）、中性粒细胞减少（2%）和白细胞减少（1%）。头痛（9%）和呕吐（8%）是最常见的非血液学3/4级不良事件。替莫唑胺耐受性良好，并在治疗MM脑转移瘤中表现出活性。需要进一步评价替莫唑胺联合治疗。(C)2004年，美国临床肿瘤学会。
Purpose. Temozolomide is a well-tolerated oral alkylating agent with activity in the CNS. A multicenter, open-label, phase II study was conducted to assess the safety and efficacy of temozolomide in patients with brain metastases from metastatic melanoma (MM) who did not require immediate radiotherapy. Patients and Methods. Eligible patients had histologically confirmed MM to the brain, and no prior radiotherapy or radiosurgery for brain metastases. Previously untreated patients received temozolomide at 200 mg/m(2)/d X 5 days, previously treated patients received 150 mg/m(2)/d X 5 days every 28 days. Treatment continued for 1 year or until disease progression or unacceptable toxicity.Results. Of 151 patients enrolled, 117 had received no prior systemic chemotherapy, and 34 had received prior chemotherapy for MM. Among previously untreated patients, 25% had more than four brain lesions, eight (7%) achieved an objective response (one complete and seven partial), and 34 (29%) had stable disease in brain metastases. Median overall survival was 3.5 months. Among previously treated patients, 21% had more than four brain lesions, one had a partial response, and six (18%) had stable disease in brain metastases. Median overall survival was 2.2 months, Temozolomide was well tolerated, with four (3%) patients discontinuing because of adverse events. Grade 3/4 hematologic toxicities included thrombocytopenia (3%), neutropenia (2%), and leukopenia (1 %. Headache (9%) and vomiting 8%) were the most common nonhematologic grade 3/4 adverse events.Conclusion. Temozolomide was well tolerated and demonstrated activity in the treatment of brain metastases from MM. Further evaluation of temozolomide combination therapy is warranted. (C) 2004 by American Society of Clinical Oncology.