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Doxorubicin-Eluting Beads (DC Bead, DC Bead M1 and Radiopaque DC Bead) for Hepatocellular Carcinoma

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Doxorubicin-Eluting Beads (DC Bead, DC Bead M1 and Radiopaque DC Bead) for Hepatocellular Carcinoma Horizon Scanning Research November 2015 & Intelligence Centre Doxorubicin-eluting beads (DC Bead, DC Bead M1 and Radiopaque DC Bead) for hepatocellular carcinoma LAY SUMMARY Hepatocellular carcinoma is the most common type of liver cancer. This briefing is Most cases of hepatocellular carcinoma are caused by cirrhosis, a based on condition associated with damage and scarring to the liver. This is information available at the time often caused by excessive alcohol intake or having long term of research and a infections with hepatitis B or C. It is more common in men than women limited literature and typically affects older people. search. It is not intended to be a DC Bead consists of beads that are designed to release doxorubicin, a definitive statement chemotherapy drug, at a slow rate at the site of the cancer. This is on the safety, delivered directly to the hepatic artery, a blood vessel that supplies efficacy or blood to the liver. Studies have shown that DC Bead delivers effectiveness of the doxorubicin to the tumour without the drug spreading to healthy tissue. health technology covered and should DC Bead is already used to treat hepatocellular carcinoma in the UK. not be used for commercial purposes or NIHR HSRIC ID: 7219 (and 11780) commissioning without additional information. This briefing presents independent research funded by the National Institute for Health Research (NIHR). The views expressed are those of the author and not necessarily those of the NHS, the NIHR or the Department of Health. NIHR Horizon Scanning Research & Intelligence Centre, University of Birmingham. Email: [email protected] Web: www.hsric.nihr.ac.uk Horizon Scanning Research & Intelligence Centre TARGET GROUP • Hepatocellular carcinoma (HCC): doxorubicin delivered using transarterial chemoembolisation (TACE). TECHNOLOGY DESCRIPTION Doxorubicin-eluting beads (DC Bead, DC Bead M1 and radiopaque DC Bead) are used during TACE therapy for the treatment of HCC. The majority of the blood supply to the normal liver parenchyma comes from the portal vein, whereas blood flow to the tumour typically comes mainly from the hepatic artery. Furthermore, HCC tumours are generally hypervascular compared with the surrounding normal parenchymaa. TACE involves the intra-arterial injection of polyvinyl alcohol beads or particles loaded with a chemotherapeutic agent around a tumour. The blood supply to the tumour is then reduced or ceases altogether, causing it to shrink or die. The reduced blood supply also allows the chemotherapeutic agent to remain at the site of the tumour longer, exposing the tumour cells to higher levels of the chemotherapeutic and reducing the peak systemic plasma levels1. DC Bead can be loaded with a dose of up to 37.5mg doxorubicin per ml. A maximum total dose of 150mg of doxorubicin per procedure is recommended. DC Bead also comes in a smaller version, DC Bead M12,3., and a radiopaque version of DC Bead. DC Bead has already received a CE mark and has been available in the UK since 2004. The use of doxorubicin in TACE is an established procedure for the treatment of HCC. DC Bead loaded with doxorubicin is sometimes referred to as DEBDOX, which was trademarked by Bio UK in December 2009a. INNOVATION and/or ADVANTAGES Doxorubicin-eluting beads offer an additional approach to TACE therapy for patients with hepatocellular cancer. DEVELOPER Biocompatibles UK Limited, a wholly owned subsidiary of BTG. AVAILABILITY, LAUNCH OR MARKETING • DC Bead was first CE Marked by Biocure Inc in 2003. The company was then taken over by Bio UK in 2004, and DC Bead is available and used in the UK. • Radiopaque DC Bead - a radiopaque embolic drug eluting bead. • DC Bead is currently registered with CE Mark as a Class IIb product. a Company comment. 2 Horizon Scanning Research & Intelligence Centre PATIENT GROUP BACKGROUND HCC is a malignant tumour arising from liver cells (hepatocytes) and occurs mainly in cirrhotic livers4. It is sometimes known as hepatoma and is usually confined to the liver, although occasionally it spreads to other organs5. The liver plays an important role in the storage of nutrients, the production of bile and protein, and the breakdown of harmful and waste products6. HCC affects more men than women and the incidence increases with age6. HCC almost always develops from chronic liver disease, mainly alcoholic or viral (hepatitis B or C) and presents with cirrhosis in about 90% of casesb. Other risk factors include insulin resistance associated with non-alcoholic steatohepatitis, diabetes, and obesity7, as well as smoking, infections and alcohol consumption6. NHS or GOVERNMENT PRIORITY AREA This topic is relevant to: • Improving Outcomes: A Strategy for Cancer (2011). • NHS England. 2013/14 NHS Standard Contract for Cancer: Chemotherapy (Adult). B15/S/a. • NHS England. 2013/14 NHS Standard Contract for Cancer: Radiotherapy (All Ages). B01/S/a. • NHS England. 2013/14 NHS Standard Contract for Hepatobiliary and Pancreas (Adult). A02/S/a. • NHS England. 2013/14 NHS Standard Contract for Liver Transplantation Service (Adult). A02/S(HSS)/a. CLINICAL NEED and BURDEN OF DISEASE Liver cancer is the 18th most commonly diagnosed cancer in the UK, accounting for 1% of all new cases of cancer8, a figure that is continuing to rise. In 2013, there were 4,387 new cases of liver cancer in England, 2,799 (64%) in males and 1,588 (36%) in females9. HCC is the main type of primary liver cancer, accounting for about 85% of cases10. Most cases of HCC are secondary to either a viral infection (hepatitis B or C) or cirrhosis11. The incidence of HCC has increased in recent years as a result of the rising prevalence of infection with hepatitis C virus and increased alcohol consumption11,12. Approximately 40-50% of HCCs in Europe can be attributed to excessive alcohol consumption13. In 2013-14 there were 10,184 admissions for HCC (ICD-10 C22.0) in England, resulting in 61,415 bed days and 14,408 finished consultant episodes14. During 2014, there were 4,452 registered deaths from HCC in England and Wales15. b Company comment. 3 Horizon Scanning Research & Intelligence Centre PATIENT PATHWAY RELEVANT GUIDANCE NICE Guidance • NICE technology appraisal. Sorafenib for the treatment of advanced hepatocellular carcinoma (TA189). May 2010. • NICE interventional procedure guidance. Chemosaturation via percutaneous hepatic artery perfusion and hepatic vein isolation for primary or metastatic liver cancer (IPG488). May 2014. • NICE interventional procedure guidance. Selective internal radiation therapy for primary hepatocellular carcinoma (IPG460). July 2013. • NICE interventional procedure guidance. Irreversible electroporation for treating primary liver cancer (IPG444). February 2013. • NICE interventional procedure guidance. Ex-vivo hepatic resection and reimplantation for liver cancer (IPG298). April 2009. • NICE interventional procedure guidance. Microwave ablation of hepatocellular carcinoma (IPG214). March 2007. • NICE interventional procedure guidance. Radiofrequency-assisted liver resection (IPG211). February 2007. • NICE interventional procedure guidance. Laparoscopic liver resection (IPG135). July 2005. • NICE interventional procedure guidance. Radiofrequency ablation of hepatocellular carcinoma (IPG2). July 2003. Other Guidance • European Society for Medical Oncology. Hepatocellular Carcinoma: ESMO-ESDO Clinical Practice Guidelines. 201216. • American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma: An Update. 201117. CURRENT TREATMENT OPTIONS For the majority of patients with HCC, treatment is palliative rather than curative. The only potentially curative options for HCC are surgery or ablation in selected patients. Treatments include: • Sorafenib – considered the standard of care for advanced HCC with well-preserved liver function by some authorities16, but is not recommended by NICE7. • Chemotherapy – doxorubicin is a commonly used chemotherapy drug and may help to shrink the size of the tumour in HCC18. Other chemotherapy drugs that may be used include cisplatin, fluorouracil and gemcitabine18. • Chemoembolisation – TACE used with doxorubicin or cisplatin18,19. TACE is the most widely used primary treatment for HCC not amenable to curative treatment by excision or ablationc. TACE is recommended for patients with BCLCd stage B (intermediate), or those with an excellent liver function and multinodular asymptomatic tumours without macroscopic vascular invasion or extra hepatic spread, however, it cannot be used as a 16 single modality treatment to cure intermediate HCC . Studies with DEBDOX suggest c Company comment. d Barcelona Clinic Liver Cancer (BCLC) staging system. 4 Horizon Scanning Research & Intelligence Centre there is less leakage of chemotherapy into the systemic circulation than conventional TACE, resulting in fewer side effects, with at least the same activity in randomised phase II trials16. • Hepatic resection – surgery is the most effective treatment for primary liver cancer18 and the standard treatment for HCC20. • Liver transplantation – to be eligible, the tumour size must be ≤5cm (single tumour), or a single tumour between 5-7cm for at least 6 months or two to three tumours that are <3cm18. • Radiofrequency ablation – more effective for treating small HCCs (≤5cm in diameter). In certain scenarios, it has also demonstrated clinical effectiveness equal to surgical resections19. EFFICACY and SAFETY Trial PRECISION V, NCT00261378, CA1008; PRECISION I; DC Bead; phase I/II. DC Bead with doxorubicin
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