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TIMP-1 is significa...
TIMP-1 is significantly associated with objective response and survival in metastatic colorectal cancer patients receiving combination of irinotecan, 5-fluorouracil, and folinic acid
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Sørensen, Nanna M (author)
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Byström, Per (author)
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Christensen, Ib J (author)
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- Berglund, Åke (author)
- Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,GI
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Nielsen, Hans Jørgen (author)
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Brünner, Nils (author)
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- Glimelius, Bengt (author)
- Karolinska Institutet,Uppsala universitet,Institutionen för onkologi, radiologi och klinisk immunologi,GI
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(creator_code:org_t)
- 2007
- 2007
- English.
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In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:14, s. 4117-4122
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http://www.ncbi.nlm....
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Purpose: Tissue inhibitor of metalloproteinase-1 (TIMP-1) is known to protect cells against apoptosis. We raised the hypothesis that elevated tumor tissue levels and thereby plasma levels of TIMP-1 would predict resistance to apoptosis-inducing chemotherapy. Experimental Design: Ninety patients with metastatic colorectal cancer were included in the study. Plasma TIMP-1 and serum carcinoembryonic antigen (CEA) were measured in samples obtained before the first cycle of chemotherapy. Results: Analysis of best objective response (complete or partial response versus stable or progressive disease) showed that patients with low plasma TIMP-1 had higher probability of obtaining an objective response [odds ratio (OR), 3.5; 95% confidence interval (95% CI), 1.4-8.5, P = 0.007]. CEA treated as a continuous variable was also a statistically significant predictor of no response (OR, 1.3; 95% CI, 1.0-1.7, P = 0.02, area under the curve 0.66) but much less so. Plasma TIMP-1 was the only significant covariate in a multivariable analysis of best objective response (OR, 3.6; 95% CI, 1.4-9.5; P = 0.001). Plasma TIMP-1 scored as a continuous variable on the log scale (loge) was significantly associated with overall survival [OS; hazard ratio (HR), 3.8; 95% CI, 2.4-5.9; P < 0.0001] and with time to progression (TTP; HR, 1.5; 95% CI, 1.0-2.3; P = 0.048). Multivariable analysis showed that plasma TIMP-1 was significant for OS when including routine clinical baseline covariates (HR, 3.5; 95% CI, 2.1-5.8; P < 0.0001). A multivariable analysis including TTP instead of OS showed that only plasma TIMP-1 was retained in the model (HR, 1.5). CEA was not significantly associated with TTP or OS when TIMP-1 was included in the model. Conclusion: This study shows that plasma TIMP-1 levels are significantly and independently associated with objective response, TTP, and OS in patients with metastatic colorectal cancer receiving combination chemotherapy.
Keyword
- metastatic colorectal cancer
- plasma TIMP-1
- chemoresistance
- prognosis
- MEDICINE
- MEDICIN
Publication and Content Type
- ref (subject category)
- art (subject category)
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