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
Journal of Gastrointestinal Surgery, 05/21/2012
Martin RCG et al. – Concomitant drug–eluting beads irinotecan (DEBIRI) and FOLFOX±bevacizumab is safe, with a minimal adverse event rate, no dose–limiting toxicities, and enhanced overall response rate.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.
- 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.