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.