A phase II study of bortezomib in the treatment of metastatic malignant melanoma
A phase II study of bortezomib in the treatment of metastatic malignant melanoma
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DOI：
10.1002/cncr.21108
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发表时间：
2005-06-15
期刊：
影响因子：
6.2
通讯作者：
Erlichman, C
中科院分区：
文献类型：
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作者：
Markovic, SN;Geyer, SM;Erlichman, C
背景硼替佐米是一种蛋白酶体抑制剂，具有可控的临床毒性和抗黑色素瘤活性的实验室证据。因此，它被认为是转移性黑色素瘤患者的临床试验。转移性黑色素瘤且血液学、肾和肝功能良好的患者接受硼替佐米治疗（1.5 mg/m2静脉推注，每周两次，每3周一次，共2周）。符合条件的患者年龄≥ 18岁，东部肿瘤协作组体能状态评分为0-1。本研究的主要目的是评估这些患者18周无疾病进展生存率和硼替佐米的耐受性。本研究旨在治疗45例患者。由于临床疗效不足的早期证据，在计划的中期分析时关闭。入组了27例患者，中位年龄为56岁（范围：32-77岁）。对治疗无重大临床应答。仅6例患者（22%）病情稳定。在这6例患者中，4例在4个周期的治疗后仍然稳定，但由于毒性而从研究中移除。至疾病进展的中位时间为1.5个月（95%置信区间[95% CI]，1.4-1.6），中位总生存期为14.5个月（95% CI，9-22）。在硼替佐米治疗失败后，大多数患者继续进行其他临床试验。26例患者可评价毒性。1例患者因其他原因退出研究，无法返回接受周期评价，因此从未接受评价。在26例患者中，未报告4/5级治疗相关毒性（使用美国国家癌症研究所通用毒性标准[版本2.0]）。11例患者（42%）发生3级毒性（认为至少可能与治疗相关），包括感觉神经病变、血小板减少症、便秘、疲乏、肠梗阻、腹痛和感染（不伴中性粒细胞减少）。患者接受的中位治疗周期数为2个（范围：1 - 6个治疗周期）。2例患者（7%）在1个治疗周期内因不良事件发生1次给药延迟，6例患者（22%）发生剂量降低。单药硼替佐米，每周两次，每3周一次，剂量为1.5 mg/m2，未发现对转移性黑色素瘤患者有效。(c)2005年美国癌症协会。
BACKGROUND. Bortezomib is a proteasome inhibitor with manageable clinical toxicity and laboratory evidence of anti-melanoma activity. Therefore, it was considered for clinical testing in patients with metastatic melanoma.METHODS. Patients with metastatic melanoma and adequate hematologic, renal, and hepatic function were treated with bortezomib (a 1.5-mg/m(2) intravenous bolus twice weekly for 2 of every 3 weeks). Eligible patients were age >= 18 years with an Eastern Cooperative Oncology Group performance status of 0-1. The primary goal of the current study was to evaluate the 18-week disease progression-free survival rate and tolerability of bortezomib in these patients.RESULTS. The current study was intended to treat 45 patients. It was closed at the planned interim analysis due to early evidence of insufficient clinical efficacy. Twenty-seven patients with a median age of 56 years (range, 32-77 years) were accrued. There were no major clinical responses to treatment. Only 6 patients (22%) achieved stable disease. Of these 6 patients, 4 were still stable after 4 cycles of treatment, but were removed from the study due to toxicity. The median time to disease progression was 1.5 months (95% confidence interval [95% CI], 1.4-1.6) with a median overall survival of 14.5 months (95% CI, 9-22). Having failed bortezomib, most patients proceeded to other clinical trials. Twenty-six patients were evaluable for toxicity. One patient was removed from the study for other reasons and could not return for the cycle evaluation and thus was never evaluated. Of the 26 patients, no Grade 4/5 treatment-related toxicities (using the National Cancer Institute Common Toxicity Criteria [version 2.0]) were reported. Eleven patients (42%) had Grade 3 toxicities (believed to be at least possibly related to treatment), including sensory neuropathy, thrombocytopenia, constipation, fatigue, ileus, abdominal pain, and infection without neutropenia. The median number of treatment cycles patients received was two (range, one to six treatment cycles). Two patients (7%) had 1 dose delay and 6 patients (22%) had dose reductions during 1 treatment cycle due to adverse events.CONCLUSIONS. Single-agent bortezomib, administered twice weekly X 2 weeks, every 3 weeks at a dose of 1.5 mg/m(2), was not found to be effective in the treatment of patients with metastatic melanoma. (c) 2005 American Cancer Society.