title: High plasma TIMP-1 and serum CEA levels during combination chemotherapy for metastatic colorectal cancer are significantly associated with poor outcome.
abstract: OBJECTIVE
  To evaluate whether combination chemotherapy leads to early changes in plasma TIMP-1 and serum carcinoembryonic antigen (CEA) levels in patients with metastatic colorectal cancer (mCRC), and whether such changes relate to subsequent objective response, time to progression (TTP) and overall survival.
  
  
  METHODS
  Eighty-eight patients with mCRC were included. Blood samples were collected before initiation and after 2, 4 and 6 weeks of treatment with an irinotecan-5-fluorouracil combination. Plasma TIMP-1 and serum CEA levels were determined by validated ELISA platforms. The first response evaluation was performed after 8 weeks of chemotherapy.
  
  
  RESULTS
  Median plasma TIMP-1 and serum CEA levels did not change significantly during 6 weeks of treatment. High plasma TIMP-1 and high serum CEA levels before treatment and at weeks 2, 4 and 6 were related to poor objective response. Moreover, high levels of plasma TIMP-1 before treatment and at weeks 2 and 4 were significantly associated with short TTP, while high levels of serum CEA at week 4 were significantly associated with short TTP. Finally, high levels of plasma TIMP-1 before and during treatment were significantly associated with poor overall survival; p < 0.0001 in all 4 determinations. A similar association between serum CEA and overall survival could only be demonstrated before treatment.
  
  
  CONCLUSIONS
  Median plasma TIMP-1 or serum CEA levels do not change significantly during the first 6 weeks of chemotherapy for mCRC. The results indicate that plasma TIMP-1 in particular and serum CEA may be valuable biomarkers even in samples collected during treatment with chemotherapy.
authors.affiliation: Department of Oncology and Pathology, Karolinska Institutet, Stockholm, Sweden. bahirhadi@hotmail.com
authors.forename: Bahir
authors.initials: B
authors.lastname: Aldulaymi
authors.forename: Per
authors.initials: P
authors.lastname: Byström
authors.forename: Ake
authors.initials: A
authors.lastname: Berglund
authors.forename: Ib J
authors.initials: IJ
authors.lastname: Christensen
authors.forename: Nils
authors.initials: N
authors.lastname: Brünner
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Nielsen
authors.forename: Bengt
authors.initials: B
authors.lastname: Glimelius
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood*; D002272:Carcinoembryonic Antigen / Q000097:blood*; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D013548:Sweden; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D019715:Tissue Inhibitor of Metalloproteinase-1