Doxorubicin-eluting microspheres limit progression of hepatocellular carcinoma

Daniel B Brown

By Daniel B Brown 

Investigators from Thomas Jefferson University published a study in the February edition of the Journal of Vascular and Interventional Radiology comparing the incidence of progression of hepatocellular carcinoma when treated with either doxorubicin-eluting beads or ethiodol-based regimens using either cisplatin/adriamycin/mitomycin-c (CAM) or adriamycin alone. A total of 122 patients were reviewed: 59 were treated with adriamycin, 30 with CAM and 33 with drug-eluting beads. The groups had statistically similar demographics including Child-Pugh status, tumour/node/metastasis staging, and Barcelona Cancer Liver Clinic Scores.

Patients receiving adriamycin required significantly more treatments (mean 2.3 +/- 1.4) compared to drug-eluting beads (1.4 +/- 0.6) and CAM (1.6 +/- 0.7). Using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria, patients treated with adriamycin were significantly less likely to achieve an objective tumour response (51% of patients) compared to CAM (84%) and drug-eluting beads (82%). Finally, patients were significantly more likely develop progressive disease when treated with adriamycin (37%) compared to CAM (13%) or drug-eluting beads (9%).

The significance of this study relates to the lack of availability of a number of drugs that have been used for chemoembolization over the last several years, including ethiodol, powdered cisplatin, and powdered doxorubicin. Ethiodol is and will be available in the future. However, powdered doxorubicin has been on and off the market and powdered cisplatin has been unavailable for several years. Based on our findings, chemoembolization of hepatocellular carcinoma with CAM performed similarly to drug-eluting beads, both in regards to treatment response and disease control. These benchmarks directly correlate to survival and can improve the opportunity for patients to undergo liver transplantation, which is the best opportunity for cure. Given the lack of availability of powdered cisplatin in the United States, we would recommend drug-eluting beads over adriamycin based on these results if these are the only two options available to an interventional oncologist

Other findings of note included a similar time to progression among the three treatment groups and similar complication rates. The risk of grade III complications using the Common Terminology Criteria for Adverse Events v3.0 ranged between 2.2% and 3.3% by procedure depending on the regimen. Forty of the 122 patients (32.8%) underwent liver transplantation. Only patients treated with adriamycin had progressive disease at the time of transplant, with nearly one third of patients progressing. However, no patients in any of the three groups developed recurrent hepatocellular carcinoma following transplantation.

We consider liver transplantation to be the ultimate goal of patients treated with chemoembolization. Fortunately, there were no recurrences in the adriamycin patients even in those who progressed. While more research needs to be done to determine the relative risk of local tumour progression prior to transplantation, it is likely that patients with disease control have the best long-term outcomes. Prior research has shown that patients with locoregional therapy prior to transplantation had superior disease-free survival to a matched group not undergoing any neo-adjuvant treatment. This finding suggests that maximising tumour necrosis prior to transplant is essential to ensuring long-term survival.”

Daniel B Brown is a professor of radiology, and director of interventional radiology and lead investigator of the trial, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, USA