Review of abstracts and presentations on drug-eluting beads

Transarterial Chemoembolisation (TACE) of neuroendocrine hepatic metastases using drug-eluting beads

DeBaere et al.

This preliminary study sought to examine the feasibility, tolerance and efficacy of drug eluting beads for Trans-arterial Chemoembolisation (TACE) in patients suffering from neuroendocrine hepatic metastases.

A total of ten patients underwent 15 courses of TACE with 2 to 4ml of beads (GelSphere [DC Beads], Biocompatibles) loaded with 50 to 100 mg of doxorubicin. Clinical and symptomatic tolerance were clinically assessed, and biological tolerance was assessed with blood samples. Morphologic response was evaluated with CT. CT perfusion studies obtained before and after TACE were evaluated for Blood flow (BF) and mean transit time (MTT).

The results revealed that minor post-embolisation symptoms were found in nine of ten patients. There was a mild increase of transamines (mean SGOT/SGPT increased respectively from 24/27 IU/l before treatment, to 91/62 IU/l on day one and to 74/111 IU/l on day five after treatment). Mean total bilirubin was respectively 12, 16.7, and 15mmol/l before, one day and five days after treatment. Within one month of TACE, all three patients with neuroendocrine-related symptoms experienced a decrease of symptoms, and a decrease of tumour markers was noted in four of five patients with elevated tumour markers before TACE. Eight of ten patients' treated lesions showed a significant (p<0.05) elongation of the MTT from 3.2s before treatment to 5.7s 30 days after treatment, and a decrease of the mean BF from 476ml/100g/min before treatment to 285ml/100g/min 30 days after treatment. These changes in tumour perfusion were already detected four days after treatment and persisted for at least two months in the five of ten patients who further demonstrated a morphologic response to TACE. Differences in perfusion values were also demonstrated between treated and non-treated liver segments.

In this preliminary study, TACE with doxorubicin eluting beads was shown to be well tolerated and seems to be efficient. Perfusion CT seems promising in detecting early changes in tumour vascularisation, whereas mere morphological/RECIST criteria may fail to detect early treatment effects.

Chemoembolisation of unresectable hepatocellular carcinoma with doxorubicin loaded microspheres: First results

Stadler A, et al.

The purpose of this study was to evaluate the clinical performance of doxorubicin loaded beads in the primary treatment of HCC by chemoembolisation. Thirty unresectable HCC patients were investigated in a single centre prospective trial. The patients were treated with transarterial chemoembolisation using drug-eluting polyvinylalcohol microspheres loaded with doxorubicin (Gelspheres, Biocompatibles). According to the European Association for the Study of the Liver (EASL) criteria, six months follow-up showed complete response (CR) in 27%, partial response (PR) in 10%, stable disease (SD) in 3% and progressive disease (PD) in 40% of the patients.

According to the Response Evaluation Criteria in Solid Tumors (RECIST) the researchers obtained CR in 27%, PR in 13%, SD in 3% and PD in 40%. The 30 days mortality of all performed embolisation procedures was 1%. Major adverse events were observed in 2% (temporary liver failure and acute cholecystitis). The overall survival rate at six months was 93%.

In conclusion, it was found that transarterial chemoembolisation of patients with HCC with doxorubicin loaded microspheres was safe.

Drug-eluting particles: a promising tool to perform TACE

Bruix J

According to Bruix, drug-eluting beads is a promising tool to perform TACE (transarterial chemoembolisation). This locoregional treatment improves survival and is due to the achievement of an objective treatment response reflected by extensive tumour necrosis. However, this beneficial effect in survival may be partially offset by post-TACE syndrome, an undesirable side effect. If unresolved the impairment of quality of life may counteract the expansion of life expectancy. Additionally, since the tumour recovers again its arterial supply through newly developed collaterals, the response to treatment is lost during follow-up and TACE has to be repeated several times per year.

Given these concepts, Bruix reports that the strategy to improve the impact of TACE on survival should be based on the development of new strategies that, while increasing the anti-tumoural effect with longer duration of the response to treatment, would have a better tolerance with a low rate of side effects.

The injection of homogeneously calibrated spheres that slowly release doxorubicin induce a pronounced anti-tumoural effect that is recognised by major tumour necrosis on follow-up CTs. At the same time, the side effects due to the passage of chemotherapy to the systemic circulation are significantly diminished, and this allows an optimal tolerance to repeated treatment.

As Bruix explains, future trials should compare this novel approach vs. conventional TACE where obstruction is achieved by gelfoam injection and chemotherapy emulsified in lipiodol. Endpoint of these studies is survival while time to progression may be informative, but not so robust. Other parameters such as initial response rate or quality of life should be considered less robust and amenable to several biases.

Hepatocellular carcinoma chemoembolisation with DC Bead in 42 patients. Safety and efficacy

Malagari K

The purpose of this study was to evaluate the treatment of hepatocellular carcinoma (HCC) with DC Bead (Biocompatibles).

Forty-two patients (aged 46-81) with confirmed 4-8cm (HCCs) underwent repeat superselective embolisations.

It was found that treatment did not cause statistically significant changes in liver function. The results showed mean baseline and one-month post-embolisation values were: SGOT: 66.82±14.10 and 66.83±14.04 (p=0.68); SGPT: 90.13±26.61 and 87.19±24.11 (p=0.28). Cholecystitis (n=1; 2%) and liver abscess (n=1; 2%) were reported to be the most severe complications. Fever and pain were also observed in 75% (n=33) and 100% (n=42), respectively.

The investigators found that an overall necrosis of >90% was achieved in 15 cases (35.7%) and <50% in five (11.90%). Repeat embolisation at three months (n=31) achieved over 90% necrosis in 11 patients (26.2%) and less than 50% in only one (2.4%). Malagari et al reported that there were no increases in tumour size, and alpha-fetoprotein levels had significantly reduced post-procedure. Overall, survival at one year was 97.61%.

In conclusion, it was shown that HCC embolisation with the use of DC Beads is safe and achieves high percentages of target tumour necrosis.

Therapeutic management of patients with liver cancer

Llovet, J.M

Dr Llovet from the Mount Sinai School of Medicine, believes that early detection of hepatocellular carcinoma (HCC) allows the application of potentially curative therapies such as resection, liver transplantation and percutaneous ablation in patients with early tumours. Llovet writes that resection and transplantation achieve the best outcomes in well-selected candidates (five-year survival of 60-70%), and compete as a first option from an intention-to-treat perspective. He continues by stating that percutaneous treatments provide good results (five-year survival of 40-60%), but are unable to achieve response rates and outcomes comparable to surgical treatments, even when applied as the first option. Radiofrequency thermal ablation provides slightly better objective results rates than ethanol injection, but no survival advantages have been fully demonstrated.

Ibuprofen-loaded embolisation microspheres: quantification of their anti-inflammatory effect in a sheep uterus model

Pelage, J.P

In this study, Professor Jean-Pierre Pelage, associate professor of Radiology at the Hopital Lariboisiere, Paris, France, demonstrated that Ibuprofen (IBU)-loaded polyvinyl alcohol (PVA [Bead-Block BB, Biocompatibles]) has an anti-inflammatory action on foreign body reaction post-embolisation.

To assess the release and effect of IBU-Beads on foreign body inflammatory reaction in sheep uterus, 12 randomised hormonally-cycled ewes were embolised in the uterine arteries with 0.5ml IBU-BB (n=6) or non-loaded BB (n=6) and sacrificed at one week or three weeks (n=3 in each group). Haematoxylin-eosin staining and CD immunno-histomarking of inflammatory cell types (CD3, CD4, CD8, D21, CD45RA, D11B, CD172a), MHC-II and anti-IBU-IgG) was performed.

The results showed that IBU was still present in small amounts in IBU-BB at one week, but not quite as detectable at three weeks. At one week, there was no inflammatory response on IBU-BB and a moderate one on BB. Compared to BB, IBU-BB had significantly less lymphocytes (<0.0001, hi2 test) in HES, less CD172a (p=.0411, MW,), CD3 (p=.0111, MW), CD4 (p=.0300, MW) and MHCII (p=.0043, MW) than BB in immunno-histochemistry. At three weeks the inflammatory response on IBU-BB developed significantly while it decreased in BB. There was no or very low amounts of CD8, CD45RA and CD21 in all groups.

Therefore, the results showed that IBU-BB releases ibuprofen and have an anti-inflammatory action on foreign body reaction post-embolisation.

References

  1. Llovet JM, Burroughs A, Bruix J. Hepatocellular carcinoma: The Lancet 2003; 362:1907-17
  2. Lopez P, Villanueva A, Llovet JM. Up-dated systematic review of randomized controlled trials in hepatocellular carcinoma. 2002-2005. Alim Pharmacol Ther 2006;23:1535-47.
 

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