Haddad Tufia, Qin Rui, Lupu Ruth, Satele Daniel, Eadens Matthew, Goetz Matthew P, Erlichman Charles, Molina Julian
Division of Medical Oncology, Mayo Clinic, 200 First Street S.W., Rochester, MN, 55905, USA.
Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
Cancer Chemother Pharmacol. 2017 Jun;79(6):1221-1227. doi: 10.1007/s00280-017-3322-9. Epub 2017 May 5.
Cilengitide is a potent and selective inhibitor of the integrins αvβ3 and αvβ5. The primary objective of this phase I clinical trial was to establish the maximum tolerated dose and determine safety/tolerability of cilengitide in combination with paclitaxel in patients with advanced solid tumors. Secondary objectives included the evaluation of the preliminary clinical outcomes.
Patients with advanced solid tumors experiencing disease progression on standard treatment were assigned to two different dose levels of cilengitide (2000 mg intravenously once or twice weekly) in combination with fixed-dose, weekly paclitaxel (90 mg/m intravenously).
Twelve evaluable patients were treated per protocol. A single dose limiting toxicity (DLT) of grade 4 neutropenia was observed at the starting dose level of once weekly cilengitide. There were no grade ≥3 adverse events that occurred with >10% frequency. One patient achieved a partial response to therapy. Five patients experienced stable disease as best response, 3 of which discontinued study participation due to progressive, peripheral neuropathy.
Cilengitide in combination with paclitaxel was well tolerated. Antitumor activity was observed. The recommended phase II dose is twice weekly cilengitide (2000 mg) with weekly paclitaxel (90 mg/m). Further studies evaluating drugs that target this pathway are warranted.
西仑吉肽是一种有效的整合素αvβ3和αvβ5选择性抑制剂。该I期临床试验的主要目的是确定最大耐受剂量，并确定西仑吉肽联合紫杉醇用于晚期实体瘤患者的安全性/耐受性。次要目的包括评估初步临床疗效。
标准治疗后疾病进展的晚期实体瘤患者被分配至两种不同剂量水平的西仑吉肽（静脉注射2000mg，每周一次或两次）联合固定剂量的每周一次紫杉醇（静脉注射90mg/m）治疗。
按照方案共治疗了12例可评估患者。在每周一次西仑吉肽的起始剂量水平观察到1例4级中性粒细胞减少的剂量限制性毒性（DLT）。未发生频率>10%的≥3级不良事件。1例患者治疗后获得部分缓解。5例患者最佳疗效为疾病稳定，其中3例因进行性周围神经病变而停止参与研究。
西仑吉肽联合紫杉醇耐受性良好。观察到抗肿瘤活性。推荐的II期剂量为每周两次西仑吉肽（2000mg）联合每周一次紫杉醇（90mg/m）。有必要进一步开展评估靶向该途径药物的研究。
