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.
Frederiksen, C., Qvortrup, C., Christensen, I. J., Glimelius, B., Berglund, A., Jensen, B. V., Nielsen, S. E., Keldsen, N., Nielsen, H. J., Brünner, N., & Pfeiffer, P. (2011). Plasma TIMP-1 levels and treatment outcome in patients treated with XELOX for metastatic colorectal cancer. Annals of Oncology, 22(2), 369-375. https://doi.org/10.1093/annonc/mdq354