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Updated: May 21, 2026
Percutaneous Hepatic Perfusion (PHP) with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver
Published on: July 31, 2016
A randomized phase II study of cilengitide (EMD 121974) in patients with metastatic melanoma
Kevin B Kim1, Victor Prieto, Richard W Joseph
1Department of Melanoma Medical Oncology, MD Anderson Cancer Center, The University of Texas, Houston, Texas 77030, USA. kkim@mdanderson.org
Abstract:
Cilengitide (EMD 121974) is a selective inhibitor of integrins αvβ3 and αvβ5. The αvβ3 promotes the proliferation of tumor-associated endothelial cells and potentially the survival of melanoma cells. We conducted a randomized phase II trial in patients with metastatic melanoma to evaluate the clinical efficacy of cilengitide. Patients with stage IV or unresectable stage III melanoma who were either chemonaive or who had previously received one systemic therapy were enrolled. Patients were randomly assigned to either 500 or 2000 mg of cilengitide administered intravenously twice weekly. The primary aim of this study was to determine the progression-free survival rate at 8 weeks. Tumor samples and blood samples were collected for pharmacodynamic and pharmacokinetic studies. Twenty-nine patients were enrolled, of whom 26 were treated (14 at 500 mg and 12 at 2000 mg). Among those treated, only three were progression free at 8 weeks: two in the 500 mg arm and one in the 2000 mg arm. One patient in the 2000 mg arm showed a prolonged partial response after an initial 28% enlargement of her target lesions. The treatment was well tolerated without clinically significant adverse events. The sole responder and one of two patients with stable disease had no αvβ3 expression at baseline. Overall, αvβ3 expression was decreased by day 8 of the treatment (P=0.05). Cilengitide was well tolerated by patients in both the treatment arms but had minimal clinical efficacy as a single-agent therapy for metastatic melanoma, and the efficacy was not related to baseline αvβ3 expression.
Insights
Cilengitide, an integrin inhibitor, showed minimal clinical efficacy in metastatic melanoma patients. The drug was well-tolerated but did not significantly improve progression-free survival at 8 weeks.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Cilengitide selectively inhibits integrins αvβ3 and αvβ5.
- Integrin αvβ3 is implicated in tumor angiogenesis and melanoma cell survival.
- Metastatic melanoma remains a significant clinical challenge requiring novel therapeutic strategies.
Purpose of the Study:
- To evaluate the clinical efficacy of cilengitide in patients with metastatic melanoma.
- To determine the progression-free survival rate at 8 weeks as the primary endpoint.
- To explore the relationship between αvβ3 expression and treatment response.
Main Methods:
- A randomized phase II trial was conducted in patients with stage IV or unresectable stage III metastatic melanoma.
- Patients received either 500 mg or 2000 mg of cilengitide intravenously twice weekly.
- Pharmacodynamic and pharmacokinetic studies were performed using tumor and blood samples.
Main Results:
- Only 3 out of 26 treated patients were progression-free at 8 weeks (2 in the 500 mg arm, 1 in the 2000 mg arm).
- One patient in the 2000 mg arm achieved a prolonged partial response.
- The sole responder and one patient with stable disease lacked baseline αvβ3 expression. αvβ3 expression decreased during treatment (P=0.05).
Conclusions:
- Cilengitide was well-tolerated as a single-agent therapy for metastatic melanoma.
- The drug demonstrated minimal clinical efficacy in this patient population.
- Treatment efficacy did not correlate with baseline αvβ3 integrin expression.
