TY - JOUR
T1 - Phase II trial of infusional fluorouracil, irinotecan, and bevacizumab for metastatic colorectal cancer
T2 - Efficacy and circulating angiogenic biomarkers associated with therapeutic resistance
AU - Kopetz, Scott
AU - Hoff, Paulo M.
AU - Morris, Jeffrey S.
AU - Wolff, Robert A.
AU - Eng, Cathy
AU - Glover, Katrina Y.
AU - Adinin, Rosie
AU - Overman, Michael J.
AU - Valero, Vincete
AU - Wen, Sijin
AU - Lieu, Christopher
AU - Yan, Shaoyu
AU - Tran, Hai T.
AU - Ellis, Lee M.
AU - Abbruzzese, James L.
AU - Heymach, John V.
PY - 2010/1/20
Y1 - 2010/1/20
N2 - Purpose: We investigated the efficacy of fluorouracil (FU), leucovorin, irinotecan, and bevacizumab (FOLFIRI + B) in a phase II trial in patients previously untreated for metastatic colorectal cancer (mCRC), and changes during treatment in plasma cytokines and angiogenic factors (CAFs) as potential markers of treatment response and therapeutic resistance. Patients and Methods: We conducted a phase II, two-institution trial of FOLFIRI + B. Each 14-day cycle consisted of bevacizumab (5 mg/kg), irinotecan (180 mg/m2), bolus FU (400 mg/m2), and leucovorin (400 mg/m2) followed by a 46-hour infusion of FU (2,400 mg/m2). Levels of 37 CAFs were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, during treatment, and at the time of progressive disease (PD). Results: Forty-three patients were enrolled. Median progression-free survival (PFS), the primary end point of the study, was 12.8 months. Median overall survival was 31.3 months, with a response rate of 65%. Elevated interleukin-8 at baseline was associated with a shorter PFS (11 v 15.1 months, P = .03). Before the radiographic development of PD, several CAFs associated with angiogenesis and myeloid recruitment increased compared to baseline, including basic fibroblast growth factor (P = .046), hepatocyte growth factor (P = .046), placental growth factor (P < .001), stromal-derived factor-1 (P = .04), and macrophage chemoattractant protein-3 (P < .001). Conclusion: Efficacy and tolerability of FOLFIRI + B appeared favorable to historical controls in this single arm study. Before radiographic progression, there was a shift in balance of CAFs, with a rise in alternate pro-angiogenic cytokines and myeloid recruitment factors in subsets of patients that may represent mechanisms of resistance.
AB - Purpose: We investigated the efficacy of fluorouracil (FU), leucovorin, irinotecan, and bevacizumab (FOLFIRI + B) in a phase II trial in patients previously untreated for metastatic colorectal cancer (mCRC), and changes during treatment in plasma cytokines and angiogenic factors (CAFs) as potential markers of treatment response and therapeutic resistance. Patients and Methods: We conducted a phase II, two-institution trial of FOLFIRI + B. Each 14-day cycle consisted of bevacizumab (5 mg/kg), irinotecan (180 mg/m2), bolus FU (400 mg/m2), and leucovorin (400 mg/m2) followed by a 46-hour infusion of FU (2,400 mg/m2). Levels of 37 CAFs were assessed using multiplex-bead assays and enzyme-linked immunosorbent assay at baseline, during treatment, and at the time of progressive disease (PD). Results: Forty-three patients were enrolled. Median progression-free survival (PFS), the primary end point of the study, was 12.8 months. Median overall survival was 31.3 months, with a response rate of 65%. Elevated interleukin-8 at baseline was associated with a shorter PFS (11 v 15.1 months, P = .03). Before the radiographic development of PD, several CAFs associated with angiogenesis and myeloid recruitment increased compared to baseline, including basic fibroblast growth factor (P = .046), hepatocyte growth factor (P = .046), placental growth factor (P < .001), stromal-derived factor-1 (P = .04), and macrophage chemoattractant protein-3 (P < .001). Conclusion: Efficacy and tolerability of FOLFIRI + B appeared favorable to historical controls in this single arm study. Before radiographic progression, there was a shift in balance of CAFs, with a rise in alternate pro-angiogenic cytokines and myeloid recruitment factors in subsets of patients that may represent mechanisms of resistance.
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U2 - 10.1200/JCO.2009.24.8252
DO - 10.1200/JCO.2009.24.8252
M3 - Article
C2 - 20008624
AN - SCOPUS:75749096309
SN - 0732-183X
VL - 28
SP - 453
EP - 459
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 3
ER -