title: Impact of pre-angiogenic factors on the treatment effect of bevacizumab in patients with metastatic colorectal cancer.
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.
authors.affiliation: Medical Oncology Clinic, Izmir Katip Celebi University Ataturk Training and Research Hospital, 35360, Izmir, Turkey, ahmetdirican@yahoo.com.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Dirican
authors.forename: Yuksel
authors.initials: Y
authors.lastname: Kucukzeybek
authors.forename: Ahmet
authors.initials: A
authors.lastname: Alacacioglu
authors.forename: Umut
authors.initials: U
authors.lastname: Varol
authors.forename: Saliha
authors.initials: S
authors.lastname: Aksun
authors.forename: Ibrahim Vedat
authors.initials: IV
authors.lastname: Bayoglu
authors.forename: Lutfiye
authors.initials: L
authors.lastname: Demir
authors.forename: Eyup
authors.initials: E
authors.lastname: Coban
authors.forename: Recep
authors.initials: R
authors.lastname: Sutcu
authors.forename: Mustafa Oktay
authors.initials: MO
authors.lastname: Tarhan
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000737:chemistry*; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D000068258:Bevacizumab; D018395:CA-19-9 Antigen / Q000097:blood; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine; D002272:Carcinoembryonic Antigen / Q000097:blood; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D010071:Oxaloacetates; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D018395:CA-19-9 Antigen; D002272:Carcinoembryonic Antigen; D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D003841:Deoxycytidine; D000068258:Bevacizumab; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin