title: Biomarkers of reactive resistance and early disease progression during chemotherapy plus bevacizumab treatment for colorectal carcinoma.
abstract: Molecular markers for predicting or monitoring the efficacy of bevacizumab in patients with metastatic colorectal cancer (mCRC) remain to be identified. We have now measured the serum concentrations of 25 angiogenesis-related molecules with antibody suspension bead array systems for 25 mCRC patients both before and during treatment in a previously reported phase II trial of FOLFIRI chemotherapy plus bevacizumab. The serum concentration of vascular endothelial growth factor-A (VEGF-A) decreased after the onset of treatment (P < 0.0001), whereas that of placental growth factor increased (P < 0.0001). Significant differences in the levels of several factors (such as VEGF-A, soluble VEGF receptor-2, and interleukin-8) were apparent between responders and nonresponders during treatment. The rapid and pronounced decrease in serum VEGF-A level after treatment onset was apparent in all subjects and was independent of the baseline concentration. However, four of nine nonresponders showed a subsequent early increase in the serum VEGF-A level. Our results thus suggest that an early increase in the serum VEGF-A concentration after the initial decrease is a potential predictive marker of a poor response and reactive resistance to bevacizumab plus chemotherapy.
authors.affiliation: Department of Genome Biology, Kinki University Faculty of Medicine, Osakasayama City, Osaka, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hayashi
authors.forename: Tokuzo
authors.initials: T
authors.lastname: Arao
authors.forename: Kazuko
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Hideharu
authors.initials: H
authors.lastname: Kimura
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Togashi
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Hirashima
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Horita
authors.forename: Satoru
authors.initials: S
authors.lastname: Iwasa
authors.forename: Natsuko Tsuda
authors.initials: NT
authors.lastname: Okita
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Honma
authors.forename: Atsuo
authors.initials: A
authors.lastname: Takashima
authors.forename: Ken
authors.initials: K
authors.lastname: Kato
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakagawa
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
authors.forename: Yasuhide
authors.initials: Y
authors.lastname: Yamada
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000097:blood*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D017322:Clinical Trials, Phase II as Topic; D015179:Colorectal Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000097:blood / Q000175:diagnosis*; D011379:Prognosis; D015996:Survival Rate
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000068258:Bevacizumab; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin