Impact of pre-angiogenic factors on the treatment effect of bevacizumab in patients with metastatic colorectal cancer


Dirican A., KÜÇÜKZEYBEK Y., ALACACIOĞLU A., Varol U., AKSUN S., Bayoglu I. V., ...More

MEDICAL ONCOLOGY, vol.31, no.4, 2014 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 31 Issue: 4
  • Publication Date: 2014
  • Doi Number: 10.1007/s12032-014-0905-8
  • Journal Name: MEDICAL ONCOLOGY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Keywords: Bevacizumab, Metastatic colorectal cancer, Endothelin-1, Asymmetric dimethylarginine, ENDOTHELIAL GROWTH-FACTOR, COOPERATIVE-ONCOLOGY-GROUP, ASYMMETRICAL DIMETHYLARGININE, CARCINOEMBRYONIC ANTIGEN, 1ST-LINE TREATMENT, ZIBOTENTAN ZD4054, TUMOR-GROWTH, PHASE-III, FLUOROURACIL, OXALIPLATIN
  • Dokuz Eylül University Affiliated: Yes

Abstract

Endothelin-1 (ET-1) and asymmetric dimethylarginine (ADMA) play a major role in tumor growth and metastasis. Our aim was to determine whether there is any association between these endothelial parameters and tumor markers with the clinical outcome of bevacizumab-treated metastatic colorectal cancer (mCRC) patients in terms of response and survival. Pretreatment serum levels of ET-1, ADMA, carcinoembryonic antigen (CEA), and carbohydrate antigen (CA) 19-9 were measured in 36 chemotherapy-naive mCRC patients treated with first-line bevacizumab-based therapy. Additionally, after first cycle of treatment, serum levels of these parameters were reanalyzed. Lower baseline serum ET-1 and ADMA levels were observed in patients responding to bevacizumab-based treatment (respectively, p = 0.037, p = 0.034). Median progression-free survival (PFS) (11 vs. 6 months, p = 0.012) and overall survival (OS) (28 vs 9 months; p = 0.007) were significantly shorter in patients with high pretreatment ET-1 levels. There was a significant decrease in ET-1 and CEA levels after first treatment (p = 0.020, p = 0.012), while ADMA and CA 19-9 levels were not significantly changed. Patients with decreased posttreatment ET-1 levels were shown to have inferior PFS (6 vs 11 months, p = 0.022), but no statistically significant difference was shown with respect to OS (p = 0.141). The effect of bevacizumab on endothelin axis including the biologic basis of decreasing ET-1 levels due to bevacizumab treatment and its association with inferior outcome has to be clarified in prospective trials.