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Clinical Cancer Research 13, 3611-3616, June 15, 2007. doi: 10.1158/1078-0432.CCR-07-0268
© 2007 American Association for Cancer Research

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Cancer Therapy: Clinical

Potential Applications for Circulating Tumor Cells Expressing the Insulin-Like Growth Factor-I Receptor

Johann S. de Bono1, Gerhardt Attard1, Alex Adjei2, Michael N. Pollak3, Peter C. Fong1, Paul Haluska2, Luisa Roberts4, Carrie Melvin4, Madeline Repollet5, David Chianese5, Mark Connely5, Leon W.M.M. Terstappen5 and Antonio Gualberto4

Authors' Affiliations: 1 Royal Marsden NHS Foundation Trust, London, United Kingdom; 2 Mayo Clinic, Rochester, Minnesota; 3 McGill University and Lady Davis Research Institute, Montreal, Quebec, Canada; 4 Pfizer Global Research & Development, New London, Connecticut; and 5 Immunicon Corporation, Huntingdon Valley, Pennsylvania

Requests for reprints: Johann S. de Bono, Section of Medicine, Institute of Cancer Research, Royal Marsden Hospital, Downs Road, Sutton, Surrey SM2 5PT, United Kingdom. Phone: 44-20-8722-4028; Fax: 44-20-8642-7979; E-mail: johann.de-bono{at}icr.ac.uk.

Purpose: To detect insulin-like growth factor-IR (IGF-IR) on circulating tumor cells (CTC) as a biomarker in the clinical development of a monoclonal human antibody, CP-751,871, targeting IGF-IR.

Experimental Design: An automated sample preparation and analysis system for enumerating CTCs (CellTracks) was adapted for detecting IGF-IR–positive CTCs with a diagnostic antibody targeting a different IGF-IR epitope to CP-751,871. This assay was used in three phase I trials of CP-751,871 as a single agent or with chemotherapy and was validated using cell lines and blood samples from healthy volunteers and patients with metastatic carcinoma.

Results: There was no interference between the analytic and therapeutic antibodies. Eighty patients were enrolled on phase I studies of CP-751,871, with 47 (59%) patients having CTCs detected during the study. Before treatment, 26 patients (33%) had CTCs, with 23 having detectable IGF-IR–positive CTCs. CP-751,871 alone, and CP-751,871 with cytotoxic chemotherapy, decreased CTCs and IGF-IR–positive CTCs; these increased toward the end of the 21-day cycle in some patients, falling again with retreatment. CTCs were commonest in advanced hormone refractory prostate cancer (11 of 20). Detectable IGF-IR expression on CTCs before treatment with CP-751,871 and docetaxel was associated with a higher frequency of prostate-specific antigen decline by >50% (6 of 10 versus 2 of 8 patients). A relationship was observed between sustained decreases in CTC counts and prostate-specific antigen declines by >50%.

Conclusions: IGF-IR expression is detectable by immunofluorescence on CTCs. These data support the further evaluation of CTCs in pharmacodynamic studies and patient selection, particularly in advanced prostate cancer.




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Clin. Cancer Res.Home page
P. Haluska, H. M. Shaw, G. N. Batzel, D. Yin, J. R. Molina, L. R. Molife, T. A. Yap, M. L. Roberts, A. Sharma, A. Gualberto, et al.
Phase I Dose Escalation Study of the Anti Insulin-Like Growth Factor-I Receptor Monoclonal Antibody CP-751,871 in Patients with Refractory Solid Tumors
Clin. Cancer Res., October 1, 2007; 13(19): 5834 - 5840.
[Abstract] [Full Text] [PDF]




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Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
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Annual Meeting Education Book Cell Growth & Differentiation
Copyright © 2007 by the American Association for Cancer Research.