Plasma TIMP-1 levels and treatment outcome in patients treated with XELOX for metastatic colorectal cancer — Ann Oncol

Ann Oncol (2011) 22 (2): 369-375.
doi: 10.1093/annonc/mdq354
First published online: July 19, 2010

Plasma TIMP-1 levels and treatment outcome in patients treated with XELOX for metastatic colorectal cancer

C. Frederiksen*†, C. Qvortrup2,3,†, I. J. Christensen4, B. Glimelius5,6, Å. Berglund5,6, B. V. Jensen7, S. E. Nielsen8, N. Keldsen9, H. J. Nielsen1, N. Brünner10 and P. Pfeiffer2,3


+ Author Affiliations
1Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre
2Department of Oncology, Odense University Hospital, Odense
3Institute of Clinical Research, University of Southern Denmark, Odense
4The Finsen Laboratory, Rigshospitalet, Copenhagen Biocenter, Copenhagen, Denmark
5Department of Oncology, Radiology and Clinical Immunology, Uppsala University, Uppsala
6Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden
7Department of Oncology, Herlev University Hospital, Herlev
8Department of Oncology, Hillerød Hospital, Hillerød
9Department of Oncology, Herning Hospital, Herning
10Institute of Veterinary Disease Biology, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark


*Correspondence to: Dr C. Frederiksen, Department of Surgical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Kettegaards Allé 30, 2650 Hvidovre, Denmark. Tel: +45-2986-0064; Fax: +45-3632-3760; E-mail: frederiksen@dadlnet.dk

Received November 10, 2009.
Revision received May 21, 2010.
Accepted May 25, 2010.


Abstract
Background: The aim was to evaluate the association between plasma tissue inhibitor of metalloproteinase-1 (TIMP-1) and serum carcinoembryonic antigen (CEA) levels and outcome in patients with metastatic colorectal cancer (mCRC) receiving XELOX (combination chemotherapy with capecitabine and oxaliplatin) as first-line treatment.

Patients and methods: One hundred and twenty patients were included. Blood samples were collected before treatment and 3 weeks later before the next treatment cycle. Plasma TIMP-1 and serum CEA levels were correlated to treatment outcome.

Results: No significant associations between baseline TIMP-1 or CEA levels and best response to treatment or progression-free survival (PFS) could be demonstrated. In contrast, high baseline plasma TIMP-1 levels were associated with poor overall survival (OS), P = 0.008, hazard ratio (HR) = 1.80 [95% confidence interval (CI): 1.17–2.78]. Furthermore, increase in TIMP-1 levels from baseline to immediately before the second cycle of chemotherapy had a significant negative effect on survival (P = 0.03, HR = 1.30, 95% CI: 1.02–1.65) while a decrease in TIMP-1 was significantly associated with a higher objective response rate (P = 0.03).

Conclusions: Both high baseline and subsequent increase in TIMP-1 levels were associated with shorter OS in patients with mCRC receiving XELOX as first-line treatment, whereas baseline TIMP-1 levels were not associated with response or PFS following XELOX treatment.

Plasma TIMP-1 levels and treatment outcome in patients treated with XELOX for metastatic colorectal cancer — Ann Oncol