Randomized phase II trial of matrix metalloproteinase inhibitor COL-3 in AIDS-related Kaposi's sarcoma: An AIDS Malignancy Consortium study
Randomized phase II trial of matrix metalloproteinase inhibitor COL-3 in AIDS-related Kaposi's sarcoma: An AIDS Malignancy Consortium study
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DOI：
10.1200/jco.2005.04.2614
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发表时间：
2006-03-20
影响因子：
45.3
通讯作者：
Aboulafia, DM
中科院分区：
文献类型：
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作者：
Dezube, BJ;Krown, SE;Aboulafia, DM
目的基质金属蛋白酶（MMPs）在Kaposi肉瘤（KS）细胞中表达增高，与肿瘤转移有关。在MMP抑制剂COL-3治疗艾滋病相关KS患者的I期试验中，药物耐受性良好，观察到KS消退，与无应答者相比，应答者的MMP-2水平显著降低。本试验的目的是延长这些初步observations.Patients和方法，这是一个随机，平行组，II期研究。COL-3以两种剂量（A组接受50 mg，B组接受100 mg）中的一种口服给药，每日一次给患有AIDS相关KS的患者。抗逆转录病毒治疗是允许的，但不是必需的。获得系列肿瘤评估和MMPs的血浆水平。研究终点为进行性KS和复发性剂量限制性毒性。结果75例患者接受A组137例和B组38例。57例患者（76%）既往接受过KS治疗。33例患者（44%）有超过50处KS病变。A组的缓解率为41%，显著高于预定目标率20%（95% CI 25%-58%; P = 0.003）; B组的缓解率为29%（P =无显著性）。MMP-2和MMP-9血浆水平从基线到治疗后的最低值显著下降（MMP-2，P <0.001; MMP-9，P = 0.001）。最常见的不良反应是光敏反应和皮疹。结论COL-3 50 mg/d治疗AIDS相关KS有效且耐受性好。COL-3是治疗这种机会性AIDS肿瘤的一种有前途的药物。
Purpose Matrix metalloproteinases (MMPs) are involved in tumor metastasis and are overexpressed in Kaposi's sarcoma (KS) cells. In a phase I trial of the MMP inhibitor COL-3 in patients with AIDS-related KS, the drug was well tolerated, KS regression was observed, and MMP-2 levels decreased significantly in responders compared with nonresponders. The aim of this trial was to extend these initial observations.Patients and Methods This was a randomized, parallel-group, phase II study. COL-3 was administered orally once daily at one of two doses (group A received 50 mg and group B received 100 mg) to patients with AIDS-related KS. Antiretroviral therapy was permitted but not required. Serial tumor assessments and plasma levels of MMPs were obtained. Study end points were progressive KS and recurrent dose-limiting toxicity.Results Seventy-five patients received 137 in group A and 38 in group B. Fifty-seven patients (76%) had received prior KS therapy. Thirty-three patients (44%) had more than 50 KS lesions. The response rate in group A was 41%, which was significantly greater than the prespecified target rate of 20% (95% CI 25% to 58%; P = .003); the response rate of group B was 29% (P = not significant). There were significant declines in MMP-2 and MMP-9 plasma levels from baseline to minimum value with treatment (MMP-2, P < .001; MMP-9, P = .001). The most common adverse events were photosensitivity and rash.Conclusion COL-3 when administered as 50 mg/d, is both active and well tolerated in the treatment of AIDS-related KS. COL-3 is a promising agent for the treatment of this opportunistic neoplasm of AIDS.