Single agent chemoembolization scores over triple drug version for liver cancer

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Samdeep Mouli

Research presented in February at the Symposium on Clinical Interventional Oncology (CIO), held in conjunction with International Symposium on Endovascular Therapy (ISET), in Hollywood, USA, provides a clear shot in the arm for chemoembolization that uses doxorubicin and ethiodised oil over the triple-drug version.

The three drugs used in combination for triple-drug transarterial chemoembolization (TACE) are doxorubicin 30mg, cisplatin 100mg and mitomycin-C 30mg. The single-agent version consists of doxorubicin 75mg/m2, based on body surface area of patients with the drugs being delivered using 300–500µm Embospheres using segmental or subsegmental infusion.

The single institution study found that some groups of patients treated with single agent chemoembolization achieved significantly higher median survival than those who received treatment with triple-drug TACE. The former is also far less toxic the latter in the treatment of unresectable hepatocellular carcinoma.

“Single-agent chemoembolization with doxorubicin and ethiodised oil demonstrates acceptable efficacy compared with triple-agent chemoembolization as measured by imaging response, time to progression and overall survival,” said Samdeep Mouli, Northwestern Memorial Hospital, Chicago, USA. “Conventional TACE should remain the standard of care treatment for patients with unresectable hepatocellular carcinoma with preserved liver function,” Mouli recommended.

Some experts in interventional oncology have long questioned how triple drug TACE has become so widely used in the USA that it has become a synonym for “conventional” TACE, or the standard of care.

Speaking at the same conference in 2012, Timothy Clark, University of Pennsylvania, Philadelphia, USA, noted that the three drugs used in triple agent TACE were combined based on the unpublished pilot experience of Aigner et al who found the treatment to be active and well-tolerated in a few patients.

The retrospective study presented this year by Mouli included 337 patients with liver cancer who were treated from 2000 to 2014. Hepatitis C virus was present in 85 of the 165 patients receiving single-drug therapy and 83 of the 172 patients receiving the triple-drug therapy. With regard to time to progression, the investigators reported that the median follow-up time for the triple-drug regimen was 36.2 months and 31.2 months for the single drug regimen. It was seen that 243 patients progressed with the median time to progression being slightly longer with triple drug TACE. However, this difference was not statistically significant, being 7.9 months for the triple-drug regimen vs. 6.8 months (p=0.32) for the single-drug procedure. Results from the study also showed that in patients who were classified as Child Pugh A, median survival was 43.6 months in patients treated with the single-drug therapy compared with 17.2 months for patients treated with the three-drug chemoembolization therapy (p<0.001).

In patients who were classified as having Child-Pugh B disease, median survival among in patients who received the single-drug regimen was 27.5 months compared with 18.1 months for patients treated with the combination therapy (p=0.073). In patients with Child-Pugh C disease, median survival among patients treated with the single-drug regimen was 13.1 months compared with 8.3 months in patients treated with combination therapy (p=0.199). When the data were analysed using the Barcelona Clinic Liver Classification (BCLC), stage A patients who were treated using the single-drug therapy showed a median survival of 40.8 months compared with 28.9 months that was achieved in patients treated with the triple-drug combination (p=0.029). In BCLC stage B patients who received the single-drug treatment, there was a median survival of 36.4 months compared with 18.1 months among the patients who were given the three-drug regimen (p=0.003). The BCLC stage C patients who were given the single-drug treatment showed a median survival of 10.9 months, which was not statistically different from the survival of patients who received the triple-drug combination (nine months; p=0.600).

There were a significantly higher number of adverse events observed in patients on the triple-drug regimen.