Drug-eluting Beads Loaded With Irinotecan Research Articles

Drug-eluting beads loaded with irinotecan to treat synchronous liver-only metastases of colorectal cancer non-responsive to bevacizumab-based chemotherapy.

To evaluate the efficacy of drug-eluting beads loaded with irinotecan (DEBIRI) in colorectal cancer (CRC) patients with synchronous liver-only metastases non-responsive to bevacizumab-based chemotherapy (BBC). Fifty-eight patients were enrolled in this study. Treatment response to BBC and DEBIRI were determined by the morphological criteria and Choi's criteria, respectively. Progression-free survival (PFS) and overall survival (OS) were recorded. The correlation between pre-DEBIRI CT parameters and treatment response to DEBIRI was analyzed. CRC patients were divided into the BBC responsive group (R group) (n = 16) and the non-responsive group (n = 42), which was further divided into the NR group (23 patients who did not receive DEBIRI) and the NR+DEBIRI group (19 patients who received DEBIRI after failing BBC). Among the R, NR and NR+DEBIRI groups, the median PFS were 11, 12, and 4 months, respectively (p < 0.01); median OS were 36, 23, and 12 months, respectively (p = 0.01). In the NR+DEBIRI group, 33 metastatic lesions were treated with DEBIRI, of which 18 (54.5%) reached objective response. The receiver operating characteristic curve showed that the contrast enhancement ratio (CER) before DEBIRI could predict objective response (AUC = 0.737, p < 0.01). In CRC patients, DEBIRI can achieve acceptable objective response for liver metastases non-responsive to BBC. However, this locoregional control does not prolong survival. The pre-DEBIRI CER can predict OR in these patients. DEBIRI can act as an acceptable locoregional management in CRC patients with liver metastases non-responsive to BBC, and the pre-DEBIRI CER is a potential indicator of locoregional control.

Intra-arterial hepatic beads loaded with irinotecan (DEBIRI) with mFOLFOX6 in unresectable liver metastases from colorectal cancer: a Phase 2 study

BackgroundChemo-embolisation with drug-eluting beads loaded with irinotecan (DEBIRI) increased survival as compared with intravenous irinotecan in chemorefractory patients with liver-dominant metastases from colorectal cancer (LMCRC). First-line DEBIRI with systemic chemotherapy may increase survival and secondary resection.MethodsIn the FFCD-1201 single-arm Phase 2 study, patients with untreated, non-resectable LMCRC received DEBIRI plus mFOLFOX6. Four courses of DEBIRI were performed alternating right and left lobe or two sessions with both lobes treated during the same session.ResultsFifty-seven patients were enrolled. Grade 3–5 toxicities were more frequent when both lobes were treated during the same session (90.5% versus 52.8%). Nine-month PFS rate was 53.6% (95% CI, 41.8–65.1%). The objective response rate (RECIST 1.1) was 73.2%, and the secondary R0 surgery was 33%. With a median follow-up of 38.3 months, median OS was 37.4 months (95% CI, 25.7–45.8), and median PFS 10.8 months (95% CI, 8.2–12.3).ConclusionsFront-line DEBIRI + mFOLFOX6 should not be recommended as the hypothesised 9-month PFS was not met. However, high response rate, deep responses, and prolonged OS encourage further evaluation in strategies integrating biologic agent, in particular in patients with secondary surgery as the main goal.Clinical trial registrationNCT01839877.

Does Tumour Contrast Retention on CT Immediately Post Chemoembolization Predict Tumour Metabolic Response on FDG-PET in Patients with Hepatic Metastases from Colorectal Cancer?

Purpose The exact mechanism of action of chemoembolization with drug eluting beads loaded with irinotecan (DEBIRI) in colorectal cancer is undetermined. Posttreatment tumour contrast retention often seen on CT immediately post procedure is of indeterminate significance. This study is aimed at assessing if metabolic response on PET-CT can be related to posttreatment tumour contrast retention. Materials and Methods In this retrospective study, a total of 17 patients with a total of 55 marker lesions were recruited. Results The area of tumour contrast retention can be matched to a hypometabolic area on subsequent PET-CT in over 36 lesions (65.5%). Out of the 55 lesions, a total of 38 marker lesions in 11 patients who also had pre-DEBIRI PET-CT were analyzed for disease response. 10 out of 10 lesions that had a complete response on PET-CT were found to demonstrate contrast retention throughout the tumour. 12 out of 13 (92.3%) tumours that had a partial metabolic response on PET-CT were found to demonstrate contrast uptake in the hypometabolic area only. In the 15 lesions that had progression/no response, 13 (86.6%) demonstrated no relationship between tumour contrast retention and tumour response. There was a significant correlation between contrast retention and disease response (P < 0.001). Conclusion Our study showed that PET-CT response can be associated with post embolization contrast retention. The data suggests blood stasis, for which tumour contrast retention is a surrogate marker, is important for the PET-CT metabolic response. The authors propose that tumour contrast retention is an important embolization endpoint in DEBIRI.

Chemoembolization with CalliSpheres drug-eluting beads loaded with irinotecan in the treatment of unresectable colorectal cancer liver metastases: preliminary results in 16 cases.

BackgroundTo analyze the perioperative safety and effectiveness of chemoembolization with CalliSpheres drug-eluting beads (DEBs) loaded with irinotecan (DEBIRI) in the treatment of unresectable colorectal cancer liver metastases (CRCLM).MethodsThe clinical data of 16 colorectal cancer patients with postoperative liver metastases who were treated with chemoembolization using DEBIRI in our center from March 2017 to December 2018 were retrospectively analyzed. The treatment responses 3 and 6 months after the chemoembolization was evaluated with the modified Response Evaluation Criteria in Solid Tumors (mRECIST). The clinical complications were recorded and graded. Changes in blood cells, liver function, and tumor marker were analyzed before treatment and during follow-up.ResultsA total of 46 DEBIRI sessions were performed in 16 patients. The success rate was 100.0%. The main postoperative complications included right upper quadrant pain (76.1%), hypertension (87.0%), nausea (89.1%), and vomiting (84.8%), which were grade 1 to 2 events; one patient suffered from acute cholecystitis (2.2%), a grade 3 event. According to mRECIST, the complete response rate, partial response rate, objective response rate, and disease control rate were 0.0%, 68.7%, 68.7%, and 100.0% 3 months after chemoembolization and 0.0%, 81.2%, 81.2%, and 93.7% 6 months after the intervention. As shown by blood biochemistry, the carcinoembryonic antigen (CEA) significantly differed before treatment and during follow-up (P<0.01), while blood cells and liver function showed no significant differences (all P>0.05).ConclusionsIn this preliminary clinical study, chemoembolization with DEBIRI is safe and effective in treating unresectable CRCLM. However, more prospective multicenter clinical trials with larger sample sizes are required to confirm our findings further.

Complete pathological response of unresectable liver metastases from colorectal cancer after trans-arterial chemoembolization with drug-eluting beads loaded with irinotecan (DEBIRI) and concomitant systemic FOLFOX: A case report from the FFCD 1201 trial

Most liver metastases from colorectal cancer (CRC) are unresectable at diagnosis. Systemic chemotherapy allows secondary surgical resection in 10 to 20% of patients. Hepatic intra-arterial treatments could enhance response and resection rate. We therefore designed a prospective phase II trial testing the transarterial chemoembolization (TACE) using drug-eluting beads loaded with irinotecan (DEBIRI) with concomitant systemic FOLFOX regimen, the FFCD 1201 trial, in patients with liver limited metastatic CRC. A 48-year old patient was operated from an occlusive sigmoid adenocarcinoma. Magnetic resonance imaging showed 6 bilobar liver metastasis. The patient was considered as non-eligible for surgery initially. Patient was included in the FFCD 1201 trial and received 5 cycles of FOLFOX and 2 sessions of DEBIRI, with a quite good tolerability. Post-treatment evaluation showed a partial response and sufficient tumor shrinkage to make liver metastasis resectable. Right hepatectomy associated with wedge resection in the left liver was performed and pathological findings showed a complete pathological response (CPR). Combination of DEBIRI with FOLFOX could increase tumor shrinkage leading to secondary resection of liver metastases from CRC. This combination may also, as shown here for the first time in a patient with unresectable LM, induce CPR of all LM, known to be associated with better outcome. Our case also emphasizes the difficulty to morphologically assess pathological response and the need for new tool to better select patients who should be resected. Further results of the FFCD 1201 trial will bring more information on this new combination therapy.

Transarterial Chemoembolization of Liver Metastases from Uveal Melanoma Using Irinotecan-Loaded Beads: Treatment Response and Complications.

The purpose of this study was to evaluate treatment response and complications of transarterial chemoembolization using drug-eluting beads loaded with irinotecan (DEBIRI) in patients with liver metastases from uveal melanoma (UM). Patients treated with DEBIRI (n = 14) were retrospectively analyzed regarding overall survival, compared to patients (n = 14) treated with intravenous dacarbazine (DTIC). Median overall survival was calculated from time of diagnosis of metastatic disease (OS1) and start of treatment (OS2). Radiological response for DEBIRI was assessed according to RECIST 1.1 on contrast-enhanced computed tomography (CT), obtained 1.5 months (range 1.2-3.7) post treatment. Major complications of DEBIRI were defined according to the Society of Interventional Radiology classification for complications by outcome. In the DEBIRI group, OS1 was 14.8 months (range 3.9-47.5), and OS2 was 9.4 months (range 1.7-39). Further, 11/13 (84.6%) of these patients had progressive disease on first follow-up CT and new lesions were seen in nine. There were 12 major complications in nine patients, possibly including one case of mortality due to disseminated intravascular coagulation (DIC). For patients with liver metastases from UM, the effect on overall survival of DEBIRI alone is questionable. Compared to previous reports, the response rate of DEBIRI was poor, with new liver lesions observed in the majority of patients. Major complications possibly included one case of DIC.

Transarterial chemoembolization using DEBIRI for treatment of hepatic metastases from colorectal cancer

Purpose To establish the safety and efficacy of chemoembolization with drug eluting beads loaded with irinotecan (DEBIRI) in the treatment of hepatic metastases from colorectal cancer. Materials and Methods A retrospective analysis of DEBIRI Transarterial Chemoembolization (TACE) was performed using LC beads loaded with 100mg of irinotecan. Twenty-eight patients were treated with 47 DEBIRI TACE procedures and followed from September 2008 to February 2012. Twenty-two (78.5%) had colon cancer metastases; 6 (21.5%) had metastases from rectal cancer. Age range was 43-82 years. Male to female ratio was 17:11. m-RECIST criteria was used to assess response. The Cancer Therapy Evaluation Program Common Terminology Criteria Adverse Events (CTCAE), Version 3.0 was used for capturing toxicity. Overall and progression free survival analysis was performed using the Kaplan-Meier estimator using the SPSS 17.0 software. Results Three patients (15%) showed a complete response, 6 had a partial response (30%), disease progression was seen in 7 (35%) and 4 (20%) had stable disease; follow up CT scans were not available for 8 patients. Adverse effects (AE’s) included, nausea, abdominal pain, vomiting, epigastric pain and HTN, fever, insomnia, constipation, chest pain, pruritus, acid-base disturbances and grade 1 neutropenia; 5 patients did not have any adverse event. Median follow up was 6.9 months (range 0.2-35). The mean and median progression free survival were 5.2 months (95% CI: 3.0-7.3m) and 4.0 months (95% CI: 3.4-4.6m) respectively. The mean and median overall survival from date of first TACE procedure in our study were 14.1 months (95% CI 9.5-18.6 months) 13.3 months (95% CI 6.8-19.8 months) respectively. Conclusion DEBIRI can be used safely in the palliative treatment of hepatic metastases from mCRC. It is a well-tolerated feasible treatment option with a low AE profile.

Feasibility, safety and pharmacokinetic study of hepatic administration of drug-eluting beads loaded with irinotecan (DEBIRI) followed by intravenous administration of irinotecan in a porcine model

Irinotecan eluting embolization beads (DEBIRI) are currently being evaluated in the clinic for the treatment of colorectal cancer metastases to the liver. The aim of this study was to determine the safety and pharmacokinetics associated with two cycles of hepatic embolization using DEBIRI followed by intravenous administration of irinotecan. Pigs were embolized with DEBIRI (100–300 μm, 100 mg dose, n = 6) and blood samples taken over 24 h to determine plasma levels of irinotecan and SN-38 metabolite and for haematology and biochemistry. At 24 h an IV infusion of 250 mg/m2 of irinotecan was administered and the plasma levels taken again. This cycle was repeated 3 weeks later. A single animal was subjected to a more aggressive regimen of embolization with 200 mg bead dose and IV of 350 mg/m2 for two cycles. Three animals were sacrificed at 6 weeks and the remaining four (n = 3 standard dose, n = 1 high dose) animals at 12 weeks and detailed histopathology performed. All animals tolerated the treatments well, with only minor changes in haematological and biochemical parameters. There was no overlap in drug plasma levels observed from the bead and IV treatments when given 24 h apart and no difference between the pharmacokinetic profiles of the two cycles separated by 3 weeks. Irinotecan plasma AUC values were similar in both the embolization and IV arms of the study. Cmax values obtained during the IV arms of the study are approximately double that of the embolization arms whilst Tmax times are shorter in the IV arms, supporting extended release of drug from the beads. Bioavailability for bead-based delivery was double that for IV administration, which was attributed to reduced clearance of the drug when delivered by this route. No additive toxicity was observed as a consequence of the combined treatments. The combination of irinotecan delivery via drug eluting bead and IV was well-tolerated with no significant clinical effects. Pharmacokinetic analyses suggest the bioavailability from bead-based delivery of drug is double that of IV infusion, attributable to reduced drug clearance for the former.

Bradycardia Associated With Drug-Eluting Beads Loaded With Irinotecan (DEBIRI) Infusion for Colorectal Liver Metastases

Intra-arterial injection of drug-eluting beads loaded with irinotecan (DEBIRI) is a new treatment option being investigated, with encouraging results, for unresectable colorectal liver metastases that are refractory to systemic chemotherapy (Martin et al., Ann Surg Oncol 18:192-198, 2011). Toxicity related to DEBIRI has also been described (Martin et al., Cardiovasc Intervent Radiol 33:960-966, 2010). Nevertheless, experience and literature related to DEBIRI remain limited, and experience with this treatment is expected to increase. The purpose of this article is to describe bradycardia occurring during DEBIRI administration, which has not been reported thus far.

Pulmonary artery chemoembolization in a sheep model: Evaluation of performance and safety of irinotecan eluting beads (DEB‐IRI)

The purpose of this study was to evaluate and compare plasma pharmacokinetics, lung tissue concentration, and the potential toxicity of drug eluting beads loaded with irinotecan (DEB-IRI) in a sheep pulmonary artery chemoembolization (PACE) model. Sheep (n = 24) were embolized with DEB-IRI loaded with different doses (0, 20, 50, or 100 mg). Direct pulmonary artery (PA) injections of irinotecan were also performed at two doses (50 or 100 mg; n = 4 sheep). Irinotecan was quantified in plasma and lung tissue (liquid chromatography-fluorescence detection); pathological examination of lungs was performed 4 days or 4 weeks after PACE. Irinotecan was detected in the systemic circulation within a few minutes after PACE, for several hours in DEB-IRI 20 and DEB-IRI 50 groups, and for 24 hours for DEB-IRI 100. Both Cmax and AUC values increased significantly with dose (p = 0.0078 and p = 0.0008, respectively) after PACE. Cmax and AUC values were significantly reduced (by 80%, p = 0.0036, and by 50%, p = 0.0393, respectively) after PACE than after direct PA injection. Irinotecan was not detected in tissue 4 days after PACE. No sign of lung toxicity was observed, except a limited hemorrhagic angionecrosis seen 4 days after PACE with DEB-IRI 100. Inflammatory response on beads was moderate in all DEB-IRI groups. Compared to other routes of administration, DEB loaded with irinotecan at doses up to 100 mg was well tolerated. DEB loaded with 100 mg irinotecan seem a promising candidate for future PACE trials in patients.

Toxicity of Irinotecan-Eluting Beads in the Treatment of Hepatic Malignancies: Results of a Multi-Institutional Registry

To evaluate the predictors of toxicity of drug-eluting beads loaded with irinotecan (DEBIRI) in the treatment of hepatic malignancies. A total of 330 patients were enrolled in a prospective, open-label, multicenter, multinational, single-arm study administering two types of drug-eluting beads (DEBIRI and drug-eluting beads loaded with doxorubicin). Complications were graded by Cancer Therapy Evaluation Program's Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. All events requiring additional physician treatment or requiring extended hospital stay or readmission within 30 days were included. A total of 109 patients received 187 DEBIRI treatments (range 1 to 5 per patient). The most common histology was metastatic colorectal cancer in 76% of patients, cholangiocarcinoma in 7% of patients, and other metastatic disease in 17% of patients. There were 35 patients (19%) with irinotecan treatments who sustained 158 treatment-related adverse events, with the median CTCAE event grade being CTCAE grade 2 (range 1 to 5). The most common adverse events were postembolic symptoms (42%). Multivariate analysis identified pretreatment and treatment-related risk factors as follows: lack of pretreatment with hepatic arterial lidocaine (p = 0.005), > or = 3 treatments (p = 0.05), achievement of complete stasis (p = 0.04), treatment with >100 mg DEBIRI in 1 treatment (p = 0.03), and bilirubin >2.0 microg/dl with >50% liver involvement (p = 0.05). These factors were predictive of adverse events and significantly greater hospital length of stay. DEBIRI is safe when appropriate technique and treatment are used. Adverse events can be predicted based on pretreatment- and treatment-related factors, and their occurrence can become part of the informed consent process. Continued standardization of this treatment will lead to fewer adverse events and improved patient quality of life.