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.

Journal Article (Journal Article;Multicenter Study)

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.

Full Text

Duke Authors

Cited Authors

  • Alva, A; Slovin, S; Daignault, S; Carducci, M; Dipaola, R; Pienta, K; Agus, D; Cooney, K; Chen, A; Smith, DC; Hussain, M

Published Date

  • April 2012

Published In

Volume / Issue

  • 30 / 2

Start / End Page

  • 749 - 757

PubMed ID

  • 21049281

Pubmed Central ID

  • PMC3175265

Electronic International Standard Serial Number (EISSN)

  • 1573-0646

Digital Object Identifier (DOI)

  • 10.1007/s10637-010-9573-5


  • eng

Conference Location

  • United States