Phase II Trial of Infusional Fluorouracil, Irinotecan, and Bevacizumab for Metastatic Colorectal Cancer: Efficacy and Circulating Angiogenic Biomarkers Associated With Therapeutic Resistance

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 o...

Full description

Saved in:

Bibliographic Details
Published in:	Journal of clinical oncology Vol. 28; no. 3; pp. 453 - 459
Main Authors:	KOPETZ, Scott, HOFF, Paulo M, LIEU, Christopher, SHAOYU YAN, TRAN, Hai T, ELLIS, Lee M, ABBRUZZESE, James L, HEYMACH, John V, MORRIS, Jeffrey S, WOLFF, Robert A, ENG, Cathy, GLOVER, Katrina Y, ADININ, Rosie, OVERMAN, Michael J, VALERO, Vincete, SIJIN WEN
Format:	Journal Article
Language:	English
Published:	Alexandria, VA American Society of Clinical Oncology 20-01-2010
Subjects:	Adult Aged Angiogenesis Inducing Agents - blood Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal, Humanized Antineoplastic Combined Chemotherapy Protocols - therapeutic use Bevacizumab Biological and medical sciences Biomarkers, Tumor - blood Camptothecin - administration & dosage Camptothecin - analogs & derivatives Camptothecin - therapeutic use Colorectal Neoplasms - blood Colorectal Neoplasms - drug therapy Colorectal Neoplasms - secondary Cytokines - blood Drug Resistance, Neoplasm Female Fluorouracil - therapeutic use Gastroenterology. Liver. Pancreas. Abdomen Humans Leucovorin - therapeutic use Male Medical sciences Middle Aged Original Reports Stomach. Duodenum. Small intestine. Colon. Rectum. Anus Treatment Outcome Tumors Antineoplastic agent Rectal disease Colorectal cancer Biological marker Monoclonal antibody Metastasis Bevacizumab Angiogenesis Isomerases Cancerology Phase II trial Intestinal disease Advanced stage Neovascularization Antiangiogenic agent Topoisomerase I inhibitor Fluorouracil Camptothecin derivatives Enzyme Fluoropyrimidine derivatives Transferases Treatment efficiency DNA topoisomerase Enzyme inhibitor Malignant tumor Thymidylate synthase Colonic disease Resistance Irinotecan Vascular endothelium growth factor Treatment Antimetabolic Methyltransferases Pyrimidine derivatives Digestive diseases Cancer
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	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. We conducted a phase II, two-institution trial of FOLFIRI + B. Each 14-day cycle consisted of bevacizumab (5 mg/kg), irinotecan (180 mg/m(2)), bolus FU (400 mg/m(2)), and leucovorin (400 mg/m(2)) followed by a 46-hour infusion of FU (2,400 mg/m(2)). 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). 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). 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.
ISSN:	0732-183X 1527-7755
DOI:	10.1200/JCO.2009.24.8252