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

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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