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Investigational New Drugs

, Volume 30, Issue 2, pp 749–757 | Cite as

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

  • Ajjai Alva
  • Susan Slovin
  • Stephanie Daignault
  • Michael Carducci
  • Robert DiPaola
  • Ken Pienta
  • David Agus
  • Kathleen Cooney
  • Alice Chen
  • David C. Smith
  • Maha Hussain
PHASE II STUDIES

Summary

Background: Integrins mediate invasion and angiogenesis in prostate cancer bone metastases. We conducted a phase II study of Cilengitide, a selective antagonist of αvβ3 and αvβ5 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.

Keywords

EMD 121974 Cilengitide Non-metastatic castration resistant prostate cancer 

Notes

Acknowledgement

Cancer Therapy Evaluation Program (CTEP), PC051382, PC051375, Prostate Cancer Foundation (PCF) N008367, Veridex (formerly Immunicon Corp.)

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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Ajjai Alva
    • 1
    • 7
  • Susan Slovin
    • 2
  • Stephanie Daignault
    • 1
  • Michael Carducci
    • 3
  • Robert DiPaola
    • 4
  • Ken Pienta
    • 1
  • David Agus
    • 5
  • Kathleen Cooney
    • 1
  • Alice Chen
    • 6
  • David C. Smith
    • 1
  • Maha Hussain
    • 1
  1. 1.University of Michigan Comprehensive Cancer CenterAnn ArborUSA
  2. 2.Memorial Sloan-Kettering Cancer CenterNew YorkUSA
  3. 3.The Sidney Kimmel Comprehensive Cancer CenterJohns Hopkins School of MedicineBaltimoreUSA
  4. 4.The Cancer Institute of New JerseyNew BrunswickUSA
  5. 5.University of Southern CaliforniaLos AngelesUSA
  6. 6.National Cancer InstituteBethesdaUSA
  7. 7.Baylor College of MedicineHoustonUSA

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