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

Ann Oncol. 2011 Feb;22(2):369-75. doi: 10.1093/annonc/mdq354. Epub 2010 Jul 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Capecitabine
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / pathology
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Female
  • Fluorouracil / analogs & derivatives
  • Fluorouracil / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Oxaloacetates
  • Survival Analysis
  • Tissue Inhibitor of Metalloproteinase-1 / blood*
  • Treatment Outcome

Substances

  • Oxaloacetates
  • Tissue Inhibitor of Metalloproteinase-1
  • Deoxycytidine
  • Capecitabine
  • Fluorouracil

Supplementary concepts

  • XELOX