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

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)3611-3616
Number of pages6
JournalClinical Cancer Research
Volume13
Issue number12
DOIs
StatePublished - Jun 15 2007

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Circulating Neoplastic Cells
IGF Type 1 Receptor
Somatomedins
docetaxel
Prostate-Specific Antigen
Prostatic Neoplasms
Accidental Falls
Drug Therapy
Retreatment
Antibodies
figitumumab
Patient Selection
Fluorescent Antibody Technique
Epitopes
Healthy Volunteers
Research Design
Therapeutics
Cell Count
Biomarkers
Monoclonal Antibodies

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Potential applications for circulating tumor cells expressing the insulin-like growth factor-I receptor. / De Bono, Johann S.; Attard, Gerhardt; Adjei, Alex; Pollak, Michael N.; Fong, Peter C.; Haluska, Paul; Roberts, Luisa; Melvin, Carrie; Repollet, Madeline; Chianese, David; Connely, Mark; Terstappen, Leon W M M; Gualberto, Antonio.

In: Clinical Cancer Research, Vol. 13, No. 12, 15.06.2007, p. 3611-3616.

Research output: Contribution to journalArticle

De Bono, JS, Attard, G, Adjei, A, Pollak, MN, Fong, PC, Haluska, P, Roberts, L, Melvin, C, Repollet, M, Chianese, D, Connely, M, Terstappen, LWMM & Gualberto, A 2007, 'Potential applications for circulating tumor cells expressing the insulin-like growth factor-I receptor', Clinical Cancer Research, vol. 13, no. 12, pp. 3611-3616. https://doi.org/10.1158/1078-0432.CCR-07-0268
De Bono, Johann S. ; Attard, Gerhardt ; Adjei, Alex ; Pollak, Michael N. ; Fong, Peter C. ; Haluska, Paul ; Roberts, Luisa ; Melvin, Carrie ; Repollet, Madeline ; Chianese, David ; Connely, Mark ; Terstappen, Leon W M M ; Gualberto, Antonio. / Potential applications for circulating tumor cells expressing the insulin-like growth factor-I receptor. In: Clinical Cancer Research. 2007 ; Vol. 13, No. 12. pp. 3611-3616.
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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.",
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AU - De Bono, Johann S.

AU - Attard, Gerhardt

AU - Adjei, Alex

AU - Pollak, Michael N.

AU - Fong, Peter C.

AU - Haluska, Paul

AU - Roberts, Luisa

AU - Melvin, Carrie

AU - Repollet, Madeline

AU - Chianese, David

AU - Connely, Mark

AU - Terstappen, Leon W M M

AU - Gualberto, Antonio

PY - 2007/6/15

Y1 - 2007/6/15

N2 - 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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