Concomitant capecitabine with hepatic delivery of drug eluting beads in metastatic colorectal cancer.

BACKGROUND: Effectiveness and toxicity of transcatheter arterial injection of irinotecan-eluting beads (DEBIRI) with and without concurrent capecitabine in pre-treated patients with metastatic colorectal cancer (CRC). PATIENTS AND METHODS: An Institutional Review Board-approved, multi-institutional registry from 5/2008 to 8/2013 was reviewed. Patients who received DEBIRI with (X-DEBIRI) or without (DEBIRI) capecitabine were compared. RESULTS: Twenty-two X-DEBIRI and 149 DEBIRI patients were compared. There was no difference in the two groups with regards to adverse events (p=0.56). During a 3- and 6-month evaluation, the disease control rate (DCR) was similar in both groups. During the 12-month evaluation, there was better DCR in the X-DEBIRI group (p=0.03). Median survival was 13 months in the DEBIRI group and 22 months in the X-DEBIRI group (log-rank test, p=0.217). CONCLUSION: There is no additional toxicity when adding capecitabine with DEBIRI. Concurrent capecitabine may offer more durable disease control rate compared to DEBIRI-alone. Survival benefit with concurrent capecitabine was not statistically significant but there may be a trend towards improved survival.

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.

PURPOSE: 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. DESIGN: 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. CONCLUSION: Concomitant DEBIRI and FOLFOX±bevacizumab is safe, with a minimal adverse event rate, no dose-limiting toxicities, and enhanced overall response rate.

Optimal outcomes for liver-dominant metastatic breast cancer with transarterial chemoembolization with drug-eluting beads loaded with doxorubicin.

The purpose of this study was to evaluate the efficacy of image-guided delivery of locoregional chemotherapy to breast cancer hepatic metastases using doxorubicin-loaded drug-eluting beads (DEBDOX). An IRB-approved multi-center, prospective, open, non-controlled repeat treatment registry to investigate the safety and efficacy of doxorubicin microspheres in the treatment of patients with unresectable liver metastasis from breast cancer was reviewed. Statistical analysis was performed with differences of P < 0.05 considered significant. About 40 patients with metastatic breast cancer (MBC) to the liver underwent a total of 75 image-guided procedures with hepatic arterial drug-eluting beads loaded with doxorubicin (DEBDOX). Treatment was well tolerated with a total of eight patients sustaining 13 adverse events within the 30 days of each treatment session. All adverse events were either a grade I or grade II in toxicity. After a median follow-up of 12 months in all patients, the hepatic progression-free survival was a median of 26 months and overall survival was a median of 47 months. The treatment of hepatic metastasis from MBC using DEBDOX is an effective local therapy with very high response rates and a very safe toxicity profile. In comparison to chemotherapy alone, consideration of hepatic-directed therapy is warranted in patients with liver-dominant metastatic disease.

Hepatic intra-arterial injection of drug-eluting bead, irinotecan (DEBIRI) in unresectable colorectal liver metastases refractory to systemic chemotherapy: results of multi-institutional study.

INTRODUCTION: Response rates and overall outcome for patients who have failed first-line and in some cases second-line chemotherapy are as low as 12% and 7 months, respectively. The aim of this study is to evaluate the efficacy of hepatic arterial sulfonate hydrogel microsphere (drug-eluting beads), irinotecan preloaded therapy (DEBIRI) in metastatic colorectal cancer refractory to systemic chemotherapy. METHODS: This was a multicenter multinational single-arm study of metastatic colorectal cancer patients who received DEBIRI after failing systemic chemotherapy from 10/2006 to 8/2008. Primary endpoints were safety, tolerance, tumor response rates, and overall survival. RESULTS: Fifty-five patients who had received prior systemic chemotherapy and who underwent a total of 99 DEBIRI treatments were reviewed. The median number of DEBIRI treatments was 2 (range 1-5), median treatment dose was 100 mg (range 100-200 mg), with total hepatic treatment of 200 mg (range 200-650 mg), with 86% of treatments performed as lobar infusion and 30% of patients treated with concurrent simultaneous chemotherapy. Adverse events occurred in 28% of patients with median grade of 2 (range 1-3) with no deaths at 30 days post procedure. Response rates were 66% at 6 months and 75% at 12 months. Overall survival in these patients was 19 months, with progression-free survival of 11 months. CONCLUSIONS: Hepatic arterial drug-eluting bead, irinotecan (DEBIRI) was safe and effective in treatment of metastatic colorectal cancer (MCC) refractory to multiple lines of systemic chemotherapy. DEBIRI is an acceptable therapy for treatment of metastatic colorectal cancer to the liver.

Surgical downstaging and neo-adjuvant therapy in metastatic colorectal carcinoma with irinotecan drug-eluting beads: a multi-institutional study.

BACKGROUND: Neoadjuvant chemotherapy for potentially resectable metastatic colorectal cancer (MCC) is becoming a more common treatment algorithm. The aim of the present study was to evaluate the efficacy of precision hepatic arterial Irinotecan therapy in unresectable MCC. METHODS: An open-label, multi-centre, multi-national single arm study of MCC patients, who received hepatic arterial irinotecan. Primary endpoints were safety, tolerance and metastatic tumour resection. RESULTS: Fifty-five patients with metastatic colorectal to the liver underwent a total of 90 hepatic arterial irinotecan treatments. The extent of liver involvement was < 25% in 75% of the patients (n= 41), between 26 and 50% in 15% of the patients (n= 11) and >50% in 10% of the patients (n= 24). The median number of hepatic lesions was four (range 1-20), with a median total size of all target lesions of 9 cm (range 5.5-28 cm) with 50% of patients having bilobar tumour distribution. The median number of irinotecan treatments was two (range 1-5). The median treatment dose was 100 mg (range 100-200) with a median total hepatic treatment of 200 mg (range 200-650). The majority of treatments (86%) were performed as lobar infusion treatments, and 30% of patients were treated with concurrent simultaneous chemotherapy. Eleven (20%) patients demonstrated significant response and downstage of their disease or demonstrated stable disease without extra-hepatic disease progression allowing resection, ablation or resection and ablation. There were no post-operative deaths. Post-operative complications morbidity occurred in 18% of patients, with none of them hepatic related. Non-tumorous liver resected demonstrated no evidence of steatohepatitis from the irinotecan arterial infusion. CONCLUSIONS: Hepatic arterial infusion irinotecan drug-eluting beads is safe and effective in pre-surgical therapy and helpful in evaluating the biology of metastatic colorectal cancer to the liver prior to planned hepatic resection.

Transarterial Chemoembolization of Metastatic Colorectal Carcinoma with Drug-Eluting Beads, Irinotecan (DEBIRI): Multi-Institutional Registry.

The purpose of this study was to evaluate the patient tolerance and efficacy of delivering locoregional chemotherapy to metastatic colorectal (MC) hepatic metastases via hepatic trans-arterial approach using irinotecan loaded drug eluting beads. This open-label, multi-center, single arm study included 30 MC patients, who had failed first line therapy. Of the 57 total embolization sessions, 12 (21% of sessions) were associated with adverse reactions during or after the treatment. After a median followup of 9 months, response rates by modified RECIST were 75% at 3 months and 66% at 6 months. Hepatic trans-arterial therapy using Irinotecan loaded DC Bead(TM) was safe and effective in the treatment of MCC as demonstrated by a minimal complication rate and acceptable tumor response.

Transarterial chemoembolisation (TACE) using irinotecan-loaded beads for the treatment of unresectable metastases to the liver in patients with colorectal cancer: an interim report.

BACKGROUND: Following failure of standard systemic chemotherapy, the role of hepatic transarterial therapy for colorectal hepatic metastasis continues to evolve as the experience with this technique matures. The aim of this study to gain a better understanding of the value of drug eluting bead therapy when administered to patients with unresectable colorectal hepatic metastasis. METHODS: This was an open-label, multi-center, single arm study, of unresectable colorectal hepatic metastasis patients who had failed standard therapy from 10/2006-10/2008. Patients received repeat embolizations with Irinotecan loaded beads(max 100 mg per embolization) per treating physician's discretion. RESULTS: Fifty-five patients underwent 99 treatments using Irinotecan drug eluting beads. The median number of total treatments per patient was 2(range of 1-5). Median length of hospital stay was 23 hours(range 23 hours - 10 days). There were 30(30%) sessions associated with adverse reactions during or after the treatment. The median disease free and overall survival from the time of first treatment was 247 days and 343 days. Six patients(10%) were downstaged from their original disease status. Of these, four were treated with surgery and two with RFA.Neither number of liver lesions, size of liver lesions or extent of liver replacement(25%) were predictors of overall survival. Only the presence of extrahepatic disease(p = 0,001), extent of prior chemotherapy (failed 1st and 2nd line vs > 2 line failure)(p = 0,007) were predictors of overall survival in multivariate analysis. CONCLUSION: Chemoembolization using Irinotecan loaded beads was safe and effective in the treatment of patients as demonstrated by a minimal complication rate and acceptable tumor response.