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 language | English (US) |
|---|---|
| Pages (from-to) | 3611-3616 |
| Number of pages | 6 |
| Journal | Clinical Cancer Research |
| Volume | 13 |
| Issue number | 12 |
| DOIs | |
| State | Published - Jun 15 2007 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
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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 journal › Article
}
TY - JOUR
T1 - Potential applications for circulating tumor cells expressing the insulin-like growth factor-I receptor
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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34250783291&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34250783291&partnerID=8YFLogxK
U2 - 10.1158/1078-0432.CCR-07-0268
DO - 10.1158/1078-0432.CCR-07-0268
M3 - Article
C2 - 17575225
AN - SCOPUS:34250783291
VL - 13
SP - 3611
EP - 3616
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 12
ER -