title: Irinotecan drug-eluting beads in the treatment of chemo-naive unresectable colorectal liver metastasis with concomitant systemic fluorouracil and oxaliplatin: results of pharmacokinetics and phase I trial.
abstract: OBJECTIVE
  The primary objective of this study is to evaluate the safety, tolerance, and pharmacokinetic profile of liver-directed therapy with drug-eluting beads irinotecan (DEBIRI) in combination with systemic modified FOLFOX in the treatment of unresectable liver metastases in chemotherapy-naive patients with colorectal cancer.
  
  
  METHODS
  DEBIRI, loaded with 100 mg irinotecan (100-300 μm beads), was administered via hepatic artery during the off week of FOLFOX therapy. Primary endpoints were safety, tolerance, systemic dose-limiting toxicities, and pharmacokinetics of systemic irinotecan and its active metabolite SN-38 at each infusion at 1-, 4-, and 24-h post-DEBIRI. Secondary endpoints were response rate and survival.
  
  
  RESULTS
  The ten patients have undergone at least 12 cycles of FOLFOX in combination with at least two DEBIRI bead treatments during the patients' off week. Pharmacokinetic data has demonstrated minimal detectable levels of irinotecan (18.6, 21, and 18.6 ng/ml) and SN-38 (1.06, 1.47, and 1.55 ng/ml) after the first, second, and third DEBIRI treatments, respectively. Currently, there has been only one severe device-related adverse event, a grade 3 hypertensive episode that required 1 day of observation in the hospital. The initial 9- and 12-month response rates have been 100 % (2 CR, 8 PR). Four (40 %) patients were successfully downstaged to resection and/or ablation with a median overall survival of 15.2 months.
  
  
  CONCLUSIONS
  Concomitant DEBIRI and FOLFOX±bevacizumab is safe, with a minimal adverse event rate, no dose-limiting toxicities, and enhanced overall response rate.
authors.affiliation: Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY, USA. Robert.Martin@louisville.edu
authors.forename: Robert C G
authors.initials: RC
authors.lastname: Martin
authors.forename: Charles R
authors.initials: CR
authors.lastname: Scoggins
authors.forename: Dana
authors.initials: D
authors.lastname: Tomalty
authors.forename: Marshall
authors.initials: M
authors.lastname: Schreeder
authors.forename: Tiffany
authors.initials: T
authors.lastname: Metzger
authors.forename: Clifton
authors.initials: C
authors.lastname: Tatum
authors.forename: Vivek
authors.initials: V
authors.lastname: Sharma
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000473:pathology*; D016503:Drug Delivery Systems / Q000009:adverse effects; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000627:therapeutic use; D011446:Prospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin