Techniques and experiences with Drug-Eluting Beads
Question to Dr Chamsuddin
In CHC (HCC, primary liver cancer) which bead size is recommended?
Is 75 mg of adriamicine (per vial) the most recommended dose or are possible other combinations?
Spain
Response from Dr Chamsuddin
At this point in time , in my practice, we use 50 mg of doxorubicin/vial 300-500µm, 500-700µm beads. This is based on a total dose of 100mg for two vials per embolisation. At this concentration we believe we can get a sustained release of doxorubicin over two weeks. We are looking for this sustained release and think that at the maximal loading capacity the drug may initially elute more quickly (burst effect). Some practices do use 75 mg-150mg as total dose.
The views expressed here are not those of Biocompatibles UK Ltd. Topics discussed may involve indications for which DC Bead and LC Bead are not approved.
Question to Panel
“Thank you for this wonderful opportunity to get opinions on this technique from experts in the field. The hepatocellular carcinomas that we see in South Africa tend to be in 30 something year olds and usually larger than 8 cm and irresectable. I noticed in the literature that the tumours treated with this technique may be multifocal but tend to be on average 5 cm in diameter. Is it feasible to use beaded chemo in the large patients that we see and if so what protocol of embolisation should be employed, and what is the systemic effect? The single case that I was involved in was a 28 year old with a 15cm tumour with severe pain not responsive to opiods. Subsequent to embolisation she developed severe myelosuppression requiring growth factor. She recovered unevent fully and remains by enlarge symptomatically controlled on small doses of opiates. If we can use this technique in such large tumours should the protocol be modified, lower doses more frequently, bland embolisation supplementation, more frequent treatments?”
South Africa
Response from Professor Lencioni
In my experience, treatment of large, uninodular, unresectable HCC is a challenging issue. In such patients, we are currently using a combination of RFA followed by Drug-Eluting Bead administration, 300-500 µm, 500-700µm, with 150mg of doxorubicin. This combination proved to be safe and very effective. The substantial debulking achieved with RFA will result in higher drug concentration and increased effect. Even if complete tumour ablation is not achieved, time to progression will be significantly prolonged.
Response from Dr Chamsuddin
In large tumours that we often see in our practice I still use two vials (300-500µm, 500-700µm), however would perform more frequent embolisations, i.e, once every 2-3 weeks.The myelosuppression you encountered is most likely due to a large shunt which is common in these vascular tumours and therefore there was leakage of drug in the blood stream. The nice thing about Drug-Eluting Beads is that the drug is slowly released over 14 days. That is why I would recommend repeat treatments every 2-3 weeks at two vials per treatment. I would not go to stasis as these patients can develop a very severe post embolisation syndrome.
Response from Dr Aliberti
In our experience with Drug-Eluting Beads we treat some patients with very large (larger than 15 cm) HCC and liver metastases lesions. In this case we reduce the dosage to half of the normal dose the dose. (Normal dose 75-150mg doxorubicin for HCC, 100-200mg irinotecan for colorectal mets. We also do a premedication with intravenous steroids to prevent damage of adjacent liver tissue and systemic toxicity. This therapy is given on the day of the procedure and for 5 days after treatment. A minimum of three weeks should be left between procedures.
The views expressed here are not those of Biocompatibles UK Ltd. Topics discussed may involve indications for which DC Bead and LC Bead are not approved.
Question to Panel
“What are your protocols for HCC and hepatic mets from colon Ca?
What other liver mets are you treating with the DEB? And what drug do you load for the individual tumor type?”
USA
Response from Professor Lencioni
We use RFA for small HCC tumours, 3 cm or less. In tumours larger than 3 cm, we prefer a combination of RFA and subsequent Drug-Eluting Bead administration. Such a combination is safe and very effective, with a high rate of complete response even in tumours refractory to RFA. TACE with Drug-Eluting Beads is the standard approach for multinodular tumours. We do not have protocols for liver mets ongoing.
Response from Dr Chamsuddin
Doxorubicin is a non-specific chemotherapeutic drug used for solid tumours. It therefore can be used on many metastatic tumours in the liver including colon, breast and lung, typically vascular tumours. However, in the presence of irinotecan, a specific chemotherapeutic agent for CRC, we tend to use irinotecan for colorectal mets to the liver. We load the beads over 2-2½ hours and the elution time is expected to be within a week. We have used doxorubicin in highly vascular melanoma metastatic to the liver and have had better than average results.
Response from Dr Aliberti
For the treatment of HCC we use 75-150 mg of doxorubicin preloaded in 2-4 ml of Drug-Eluting Beads. We preferably use the 100-300µm size. For the treatment of colorectal liver metastases we use 200mg of irinotecan preloaded in 4 ml of Drug-Eluting Beads (2ml 100-300µm and 2ml 300-500µm). We have treated also cholangiocarcinoma and liver mets from breast, gastric and pancreatic carcinoma, carcinoid and melanoma. The type of drug is different in each cancer.
The views expressed here are not those of Biocompatibles UK Ltd. Topics discussed may involve indications for which DC Bead and LC Bead are not approved.
Question to Dr Chamsuddin
“Are you using different particles sizes based on tumour cell type? Are you using the same size on everyone or are there criteria from the pre-op MR or CT that helps you decide particle size? Thanks.”
USA
Response from Dr Chamsuddin
In my practice we use two vials of Drug-Eluting Beads for all of our embolisations. Drug-Eluting Bead is an embolic material and we like to utilise its secondary drug-carrying capabilities. Stasis is not always our goal. We use 300-500µm and then 500-700µm.
The views expressed here are not those of Biocompatibles UK Ltd. Topics discussed may involve indications for which DC Bead and LC Bead are not approved.
Question to Panel
“Can the beads be loaded with more than one drug? Has any work been done to evaluate this?”
USA
Response from Biocompatibles UK Ltd
Multiple drugs can theoretically be loaded at the same time into the beads. The uptake of each drug into the beads will be related to their relative affinity to the charged portion within the beads or their solubility. Biocompatibles has early pre-clinical evaluations of multiple drug strategies
Topics discussed may involve indications for which DC Bead and LC Bead are not approved.
Question to Dr Aliberti
“How do choose between DC Bead loaded with irinotecan vs. Sir-Sphere radioembolisation for a patient with chemo refractory metastatic CRC?”
USA
Response from Dr Chamsuddin
In multiple innumerable mets, we tend to go with SIR spheres. In localised disease we tend to use irinotecan.
Response from Dr Aliberti
In our experience, results from loco regional therapy with Drug-Eluting Beads are equally positive in those patients with chemo refractory disease.
The views expressed here are not those of Biocompatibles UK Ltd. Topics discussed may involve indications for which DC Bead and LC Bead are not approved.
Question to Dr Chamsuddin
“We have had excellent results with hepatic art chemoembolisation for HCC. How do you decide between this treatment and LC Bead/Adriamycin embolisation in a given patient?”
USA
Response from Dr Chamsuddin
Drug-Eluting Beads present many advances over conventional TACE. In many practices, pharmacies and interventionalists do not feel comfortable dealing with the bulky mix of cisplatin, doxorubicin and ethiodol. The Drug-Eluting Bead mixture is always a constant mixture. The drug release rate is a sustainable and predictable rate in most cases. In addition, at two vials per embolisation (as it is in our practice), the entire desired dose is nearly always delivered. Conventional TACE, in most cases, does not allow delivery of the entire dose. For this reason we have shifted our chemoembolisation technique to using Drug-Eluting Beads.
The views expressed here are not those of Biocompatibles UK Ltd. Topics discussed may involve indications for which DC Bead and LC Bead are not approved.
Question to Panel
- “Do the drug-eluting beads have increased affinity for the tumours in the liver, whether primary or secondary lesions?
- What is the risk of liver failure if injection of drug-eluting beads is done from the right and left hepatic artery without selective catheterisation of the vessel(s) feeding the tumours?”
Malaysia
Response from Professor Lencioni
- Delivery of the beads is primarily related to flow. HCC is highly vascularised and therefore targeting is easier. However it is definitely possible to achieve effective bead delivery to metastatic lesions, including those that appear as relatively hypovascular.
- The risk of liver failure depends of the severity of the underlying cirrhosis at the time of the treatment. In Child A patients such a risk appears to be minimal. Patients in Child B class require more careful clinical assessment. Overall, the safety profile of the beads is higher than that of conventional TACE.
Response from Dr Chamsuddin
Drug-Eluting Beads are non-selective embolic material and do not have an “affinity” per se to the tumour. When injected non-selectively, they might flow preferentially to the vascular tumour rather than the rest of the liver. Therefore, I believe it is the vascularity of the tumour that would determine the flow and not the tumour type. When injecting both hepatic arteries at the same time, care needs to be taken as far as stasis is concerned specifically in patients with liver cirrhosis and portal hypertension. These patients depend on the hepatic arterial flow and could go into liver failure. Again, here, we recommend using two vials and try to stay away from stasis. In liver cirrhosis, we try to be as selective as possible.
Response from Dr Aliberti
In my experience Drug-Eluting Beads loaded with drug is much more effective than bland embolisation. This is mainly observed for liver metastases where the high concentrations of chemotherapy achieved locally are the main efficacy factor followed by the embolisation itself.
The risk of liver failure depends on the percentage of liver involvement by tumoural disease rather than the level of embolisation.
Simultaneous embolisation of right and left hepatic arteries induces a more severe post-embolisation syndrome.
The views expressed here are not those of Biocompatibles UK Ltd. Topics discussed may involve indications for which DC Bead and LC Bead are not approved.
Question to Panel
- “Personally I think Irinotecan 100-300 micron bead are too small. It is effective in causing tumour necrosis, but the patient seems to be quite sick as well over three weeks.
- What is the rational in recommending this size for liver mets?”
- What is the rational in recommending three weekly treatments for liver mets? Can we space treatment longer, say every four to five weeks?
Australia
Response from Dr Chamsuddin
We use 300-500µm bead size and higher. The potential problem I could foresee with smaller size beads may be their ability to infarct normal tissue at the capillary level. In my experience the release rate is higher due to the surface area and a more severe post embolisation syndrome. The rationale of closely spaced treatments is due to the elution speed of irinotecan and the half life of the drug (as given by the oncologist). We use one treatment per week rather than one every three weeks.
Response from Dr Aliberti
We use the size of 100-300µm to effectively embolise the smallest arteries and make the drug available deeper into the tumour. In our experience we perform the second TACE three or four weeks after the first, depending on the patient’s tolerance to the previous procedure.
The views expressed here are not those of Biocompatibles UK Ltd. Topics discussed may involve indications for which DC Bead and LC Bead are not approved.
Question to Panel
- “What is your end point when using the beads?
- What type of results have you had with irinotecan for CRC mets?
- What type of imaging follow-up do you recommend?”
USA
Response from Dr Chamsuddin
Our end point is again, using two vials of beads loaded with the drug. We do not try to reach stasis. We follow up all of our patients with MRI at 6 weeks post initiation of treatment. We have had good results with irinotecan so far.
Response from Dr Aliberti
We prefer not to treat patients who have a liver involvement above 60%. The evaluation on the feasibility to do the treatment depends on the patient’s clinical status. In some particular cases we have treated patients with liver involvement above 80%. The results we had seen are: excellent necrosis in the lesion and good response of the loco-regional disease, significant improvement of quality of life and prolonged survival. The contrast enhanced CT can precisely measure the results in change in vascularisation of liver metastases and also extrahepatic disease. The MRI is more costly, requires patient’s collaboration and doesn’t give information like MDCT on extrahepatic disease.
The views expressed here are not those of Biocompatibles UK Ltd. Topics discussed may involve indications for which DC Bead and LC Bead are not approved.
