Potential applications for circulating tumor cells expressing the insulin-like growth factor-I receptor.

Abstract

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.

• Authors: Johann S de Bono, Gerhardt Attard, Alex Adjei, Michael N Pollak, Peter C Fong, Paul Haluska, Luisa Roberts, Carrie Melvin, Madeline Repollet, David Chianese, Mark Connely, Leon W M M Terstappen, Antonio Gualberto
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 13 Issue 12 Pg. 3611-6 (Jun 15 2007) ISSN: 1078-0432 [Print] United States
• PMID: 17575225 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• Receptor, IGF Type 1

Topics

• Antibodies, Monoclonal (therapeutic use)
• Antineoplastic Agents (therapeutic use)
• Fluorescent Antibody Technique
• Humans
• Immunologic Techniques
• Neoplasms (drug therapy, metabolism)
• Neoplastic Cells, Circulating (metabolism)
• Receptor, IGF Type 1 (metabolism)
• Treatment Outcome