Cilengitide（EMD 121974，NSC 707544）在非转移性去势抵抗性前列腺癌患者中的 II 期研究，NCI-6735。由 DOD/PCF 前列腺癌临床试验联盟进行的研究。
Phase II study of cilengitide (EMD 121974, NSC 707544) in patients with non-metastatic castration resistant prostate cancer, NCI-6735. A study by the DOD/PCF prostate cancer clinical trials consortium.
机构信息
University of Michigan Comprehensive Cancer Center, 7314 Cancer Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5946, USA.
出版信息
Invest New Drugs. 2012 Apr;30(2):749-57. doi: 10.1007/s10637-010-9573-5. Epub 2010 Nov 4.
BACKGROUND
Integrins mediate invasion and angiogenesis in prostate cancer bone metastases. We conducted a phase II study of cilengitide, a selective antagonist of α(v)β(3) and α(v)β(5) integrins, in non-metastatic castration resistant prostate cancer with rising PSA.
METHODS
Patients were observed for 4 weeks with PSA monitoring, and then treated with 2,000 mg IV of cilengitide twice weekly until toxicity/progression. PSA, circulating tumor cells (CTCs) and circulating endothelial cells (CECs) were monitored each cycle with imaging performed every three cycles. Primary end point was PSA decline by ≥ 50%. Secondary endpoints were safety, PSA slope, time to progression (TTP), overall survival (OS), CTCs, CECs and gene expression.
RESULTS
16 pts were enrolled; 13 were eligible with median age 65.5 years, baseline PSA 8.4 ng/mL and median Gleason sum 7. Median of three cycles was administered. Treatment was well tolerated with two grade three toxicities and no grade four toxicities. There were no PSA responses; 11 patients progressed by PSA after three cycles. Median TTP was 1.8 months and median OS has not been reached. Median pre- and on-treatment PSA slopes were 1.1 and 1.8 ng/mL/month. Baseline CTCs were detected in 1/9 patients. CTC increased (0 to 1; 2 pts), remained at 0 (2 pts) or decreased (23 to 0; 1 patient) at progression. Baseline median CEC was 26 (0-61) and at progression, 47 (15-148). Low cell counts precluded gene expression studies.
CONCLUSIONS
Cilengitide was well tolerated but had no detectable clinical activity. CTCs are of questionable utility in non-metastatic prostate cancer.
背景
整合素在前列腺癌骨转移中的侵袭和血管生成中起介导作用。我们对非转移性去势抵抗性前列腺癌（伴 PSA 升高）进行了 cilengitide 的 II 期研究，cilengitide 是 α(v)β(3)和 α(v)β(5)整合素的选择性拮抗剂。
方法
患者接受 4 周 PSA 监测，然后每两周接受 2000mg 的 cilengitide 静脉滴注 2 次，直到出现毒性/进展。每个周期监测 PSA、循环肿瘤细胞（CTC）和循环内皮细胞（CEC），每三个周期进行一次影像学检查。主要终点为 PSA 下降≥50%。次要终点为安全性、PSA 斜率、无进展生存期（TTP）、总生存期（OS）、CTC、CEC 和基因表达。
结果
共纳入 16 例患者，13 例符合条件，中位年龄 65.5 岁，基线 PSA 8.4ng/ml，中位 Gleason 评分 7 分。中位治疗周期为 3 个周期。治疗耐受性良好，有 2 例 3 级毒性，无 4 级毒性。无 PSA 反应，11 例患者在 3 个周期后 PSA 进展。中位 TTP 为 1.8 个月，中位 OS 尚未达到。中位治疗前和治疗时 PSA 斜率分别为 1.1 和 1.8ng/ml/月。基线时，9 例患者中有 1 例检测到 CTC。CTC 增加（0 至 1；2 例），在进展时保持在 0（2 例）或减少（23 至 0；1 例）。基线时中位 CEC 为 26（0-61），进展时为 47（15-148）。低细胞计数使基因表达研究无法进行。
结论
cilengitide 耐受性良好，但无明显临床活性。在非转移性前列腺癌中，CTC 的作用尚不确定。
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