Irinotecan loaded in eluting beads: preclinical assessment in a rabbit VX2 liver tumor model.

PURPOSE: The purpose of this study was to study the pharmacokinetics of irinotecan injected intravenously, intra-arterially, or loaded onto a delivery platform. MATERIAL AND METHODS: Fifty-four New Zealand White rabbits with VX2 liver tumor, divided in 3 groups of 17 rabbits, each received irinotecan either by intravenous (IV) route, intra-arterial hepatic (IA) route, or loaded on drug-eluting beads (DEBIRI). Animals were killed at 1, 6, and 24 h. Irinotecan and SN-38 concentrations were measured at different time points in serum, tumor, and normal liver. RESULTS: Twelve milligrams of irinotecan were injected IV and IA, whereas 6-16.5 mg were injected loaded onto DEBIRI. Normalized serum irinotecan reached a peak of 333 ng/ml (range 198.8-502.5) for IV, 327.1 ng/ml (range 277.1-495.6) for IA, and 189.7 ng/ml (range 111.1-261.9) for DEBIRI (P < 0.001) delivery. The area-under-the-curve value from 10 to 60 min of serum irinotecan concentration was significantly lower for DEBIRI (P = 0.0009). Tumor irinotecan levels for IV, IA, and DEBIRI (in ng/200 mg of tissue followed by ranges in parentheses) were, respectively, 23.6 (0.3-24.9), 36.5 (7.7-1914.1), and 20.2 (2.9-319) at 1 h; 4.2 (1-27.9), 99.3 (46.6-159.5), and 42.1 (11.3-189) at 6 h; and 2.7 (2.5-6.9), 18.3 (1.5-369.1), and 174.4 (3.4-5147.3) at 24 h (P = 0.02). At 24 h, tumor necrosis was 25% (10-30), 60% (40-91.25), and 95% (76.25-95) for IV, IA, and DEBIRI, respectively (P = 0.03). CONCLUSION: Compared with IV or IA, DEBIRI induces lower early serum levels of irinotecan, a high and prolonged intratumoral level of irinotecan, and a greater rate of tumor necrosis at 24 h. Further evaluation of the clinical benefit of DEBIRI is warranted.

Transarterial chemoembolization of liver metastases from well differentiated gastroenteropancreatic endocrine tumors with doxorubicin-eluting beads: preliminary results.

PURPOSE: To evaluate the feasibility, safety, and efficacy of transarterial chemoembolization (TACE) of progressive liver metastases from well differentiated gastroenteropancreatic endocrine (GEP) tumors with drug-eluting beads (DEBs). MATERIALS AND METHODS: From June 2004 to July 2005, eight men and 12 women aged 34 to 75 years (mean +/- SD, 59 y +/- 12), including 13 patients with bilobar disease and seven with unilobar disease, underwent 34 sessions of TACE with DEBs (500-700 mum) loaded with doxorubicin. Morphologic response was evaluated with computed tomography (CT) at 1 and 3 months according to Response Evaluation Criteria In Solid Tumors. Clinical and laboratory data were also assessed. RESULTS: The complete dose of 4 mL of DEBs loaded with 100 mg doxorubicin was injected during 22 TACE sessions and 1-3.5 mL of DEBs was injected during 12 TACE sessions. Three months after TACE, 16 of 20 patients (80%) exhibited a partial response, three (15%) had stable disease, and one (5%) had progressive disease. The mean size of the largest metastasis in each patient decreased from 42 mm +/- 24 before treatment (median, 39.5 mm) to 33 mm +/- 23 (median, 29 mm) 1 month after treatment and 30 mm +/- 21 (median, 26.5 mm) 3 months after treatment. After a median follow-up of 15 months (range, 6-24 months), nine patients' disease remained controlled without tumor progression and 10 patients had progressive disease. The median time to progression was 15 months. Postembolization syndrome lasted less than 7 days in 23 sessions (67%) and more than 7 days in seven sessions (22%), and no symptoms at all were observed in four sessions (11%). Peak aspartate aminotransferase, alanine aminotransferase, and bilirubin levels after TACE were 35-490 IU (mean, 125 IU +/- 77; normal, <35 IU), 20-440 IU (mean, 149 IU +/- 155; normal, <45 IU), and 8-90 mol/L (mean, 26 IU +/- 25; normal, <17 IU), respectively, at 2-3 days. In five patients, follow-up CT at 1 month revealed TACE-induced peripheral liver necrosis. CONCLUSIONS: TACE with DEBs is well tolerated and appears effective. A comparative study with a standard TACE or transarterial embolization regimen is warranted to define the best protocol for transarterial treatment of GEP liver metastases.

Usefulness of guiding needles for radiofrequency ablative treatment of liver tumors.

PURPOSE: To evaluate the usefulness of a guiding needle for radiofrequency (RF) ablative treatment of liver tumors. METHODS: Forty-two patients, 38-78 years old (57 +/- 17), with 42 liver tumors (18 HCC, 24 colon cancer metastases) underwent RF ablation using a 14-gauge guiding needle with an external insulated sheath in which any 18-gauge or smaller needle can be placed, including a specially designed 3.5 cm LeVeen RF electrode. One guiding needle was used in 20 tumors to provide biopsy and RF treatment in a single puncture. Three to five guiding needles were loaded in 22 tumors measuring 35 to 64 mm in their largest diameter before starting RF treatment requiring multiple overlapping RF applications. RESULTS: In the 20 RF treatments combined with biopsy, the biopsy was always contributive. Because of pre-positioning of the sheath, postbiopsy modifications (bleeding or air artifacts) did not hinder subsequent RF treatment. The 22 large tumors received 5 to 12 RF applications (mean = 6.8) through the three to five preloaded guiding needles. The RF ablation zones measured 46 to 94 mm (mean = 55) in their largest dimension, with ablative margins in all cases. After 8 to 32 months (mean = 20), 14 of the 22 tumors are considered completely destroyed on computed tomography follow-up and one tumor seeding has been found. CONCLUSION: The Leveen CoAccess needle allows precise tumor targeting when treating large tumors requiring multiple RF applications. It allows biopsies combined with RF ablation through a single tract.