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

作者：Martin Robert C G II^*; Scoggins Charles R; Tomalty Dana; Schreeder Marshall; Metzger Tiffany; Tatum Clifton; Sharma Vivek

来源：Journal of Gastrointestinal Surgery, 2012, 16(8): 1531-1538.

DOI：10.1007/s11605-012-1892-8

• Metastatic colon cancer
• Liver-directed therapy
• Hepatic arterial therapy
• Irinotecan
• Liver-dominant metastatic colorectal cancer

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. %26lt;br%26gt;DEBIRI, loaded with 100 mg irinotecan (100-300 mu m 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. %26lt;br%26gt;The ten patients have undergone at least 12 cycles of FOLFOX in combination with at least two DEBIRI bead treatments during the patients%26apos; 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. %26lt;br%26gt;Concomitant DEBIRI and FOLFOX +/- bevacizumab is safe, with a minimal adverse event rate, no dose-limiting toxicities, and enhanced overall response rate.

• 出版日期2012-8