TY - JOUR
T1 - TIMP-1 Is Significantly Associated with Objective Response and Survival in Metastatic Colorectal Cancer Patients Receiving Combination of Irinotecan, 5-Fluorouracil, and Folinic Acid
AU - Sørensen, Nanna M
AU - Byström, Per
AU - Christensen, Ib Jarle
AU - Berglund, Åke
AU - Nielsen, Hans Jørgen
AU - Brünner, Nils
AU - Glimelius, Bengt
PY - 2007
Y1 - 2007
N2 - Purpose: Tissue inhibitor of metalloproteinase-1 (TIMP-1) is known to protect cells againstapoptosis.We raisedth e hypothesis that elevatedtu mor tissue levels and thereby plasma levelsof TIMP-1wouldp redict resistance to apoptosis-inducing chemotherapy.Experimental Design: Ninety patients with metastatic colorectal cancer were included in thestudy. PlasmaTIMP-1and serum carcinoembryonic antigen (CEA) were measured in samplesobtainedbef ore the first cycle of chemotherapy.Results: Analysis of best objective response (complete or partial response versus stable orprogressive disease) showed that patients with low plasmaTIMP-1had higher probability ofobtaining an objective response [odds ratio (OR), 3.5; 95% confidence interval (95% CI),1.4-8.5,P =0.007].CEAtreatedas a continuous variablewas also a statistically significantpredictorofno response (OR,1.3; 95%CI,1.0-1.7, P = 0.02, areaunder the curve 0.66) butmuchless so.PlasmaTIMP-1was the only significant covariate in a multivariable analysis of best objectiveresponse (OR, 3.6; 95%CI,1.4-9.5; P = 0.001). PlasmaTIMP-1scoredas a continuous variable onthe log scale (loge) was significantly associatedwith overall survival [OS; hazardr atio (HR), 3.8;95% CI, 2.4-5.9; P < 0.0001] andw ith time to progression (TTP; HR, 1.5; 95% CI, 1.0-2.3; P =0.048). Multivariable analysis showedthat plasmaTIMP-1was significant for OS when includingroutine clinical baseline covariates (HR, 3.5; 95% CI, 2.1-5.8; P < 0.0001). A multivariable analysisincludingTTP instead of OS showed that only plasmaTIMP-1was retained in the model (HR,1.5).CEA was not significantly associatedw ith TTP or OS when TIMP-1was included in the model.Conclusion: This study shows that plasmaTIMP-1 levels are significantly and independentlyassociatedw ith objective response,TTP, and OS in patients with metastatic colorectal cancerreceiving combination chemotherapy.
AB - Purpose: Tissue inhibitor of metalloproteinase-1 (TIMP-1) is known to protect cells againstapoptosis.We raisedth e hypothesis that elevatedtu mor tissue levels and thereby plasma levelsof TIMP-1wouldp redict resistance to apoptosis-inducing chemotherapy.Experimental Design: Ninety patients with metastatic colorectal cancer were included in thestudy. PlasmaTIMP-1and serum carcinoembryonic antigen (CEA) were measured in samplesobtainedbef ore the first cycle of chemotherapy.Results: Analysis of best objective response (complete or partial response versus stable orprogressive disease) showed that patients with low plasmaTIMP-1had higher probability ofobtaining an objective response [odds ratio (OR), 3.5; 95% confidence interval (95% CI),1.4-8.5,P =0.007].CEAtreatedas a continuous variablewas also a statistically significantpredictorofno response (OR,1.3; 95%CI,1.0-1.7, P = 0.02, areaunder the curve 0.66) butmuchless so.PlasmaTIMP-1was the only significant covariate in a multivariable analysis of best objectiveresponse (OR, 3.6; 95%CI,1.4-9.5; P = 0.001). PlasmaTIMP-1scoredas a continuous variable onthe log scale (loge) was significantly associatedwith overall survival [OS; hazardr atio (HR), 3.8;95% CI, 2.4-5.9; P < 0.0001] andw ith time to progression (TTP; HR, 1.5; 95% CI, 1.0-2.3; P =0.048). Multivariable analysis showedthat plasmaTIMP-1was significant for OS when includingroutine clinical baseline covariates (HR, 3.5; 95% CI, 2.1-5.8; P < 0.0001). A multivariable analysisincludingTTP instead of OS showed that only plasmaTIMP-1was retained in the model (HR,1.5).CEA was not significantly associatedw ith TTP or OS when TIMP-1was included in the model.Conclusion: This study shows that plasmaTIMP-1 levels are significantly and independentlyassociatedw ith objective response,TTP, and OS in patients with metastatic colorectal cancerreceiving combination chemotherapy.
M3 - Journal article
VL - 13
SP - 4117
EP - 4122
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 14
ER -