A randomized controlled trial of transcatheter arterial chemoembolization with lipiodol, doxorubicin and cisplatin versus intravenous doxorubicin for patients with unresectable hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is a major and often therapeutically frustrating oncological problem. A total of 100 patients with unresectable HCC were recruited and randomized to be treated with either transcatheter arterial chemoembolization (TACE) or systemic chemotherapy. Fifty patients were treated with TACE using lipiodol, doxorubicin and cisplatin, while 50 patients were treated with systemic doxorubicin alone. Patients treated with TACE achieved a significantly higher response rate, with partial response achieved in 16 patients (32%) versus five patients (10%) in the chemotherapy arm (P = 0.007). A significantly more favourable tumour response to chemoembolization was found in patients with single lesions (P = 0.02), Child class A (P = 0.007), Okuda stage 1 (P = 0.005) and alpha-feto protein less than 400 ng/mL (P < 0.001). The probability of tumour progression was significantly lower in cases treated with TACE where the median progression free survival was 32 weeks (range, 16-70 weeks) versus 26 weeks (range, 14-54 weeks) for patients treated with systemic chemotherapy (P = 0.03). However, the median overall survival did not differ significantly in cases treated with TACE (38 weeks) compared with those treated with chemotherapy (32 weeks) (P = 0.08), except for patients with serum albumin >3.3 g/dL (60 vs. 36 weeks; P = 0.003). Multivariate Cox regression analysis showed that a rise of serum albumin by 1 g/dL is associated with a decrease in the risk of death by 33% (95% confidence interval: 0.12-0.94, P = 0.038). Mortality in the chemoembolization arm was due to tumour progression in 18 patients (53%), liver failure in 11 patients (32%) and gastro intestinal tract (GIT) bleeding in 5 patients (15%). Mortality in the chemotherapy arm was due to tumour progression in 23 patients (64%), liver failure in 9 patients (25%) and GIT bleeding in 4 patients (11%). Treatment-related mortality was 4% in the TACE arm versus 0% in the chemotherapy arm. In conclusion, the overall survival benefits of TACE and systemic doxorubicin are similar for patients with unresectable HCC amenable to either treatment. It is crucial to optimize the benefit-risk ratio of TACE. In this setting, serum albumin level is a candidate marker for selection of cases who may benefit from this procedure.

Lipiodol transarterial chemoembolization for hepatocellular carcinoma: A systematic review of efficacy and safety data

“…(14,15) Hence, we were unable to update the results already presented concerning the survival benefit of TACE over no intervention. The other RCTs that were identified had different design and treatment arms and were focused on the comparison of different TACE techniques or protocols, (23)(24)(25)30) on the comparison of lipiodol TACE and either intravenous or transarterial chemotherapy (26,27) and on the use of lipiodol TACE alone versus lipiodol TACE combined with amiodarone or bevacizumab. (28,29) Median OS of HCC patients who received lipiodol TACE in this analysis-19.4 months-is consistent with the data reported in the previous metaanalyses.…”

“…(15) Three of the twelve RCTs were focused on the comparison of different doses of lipiodol, (23) different classes of iodinated contrast materials, (24) or different types of embolic agents (25) for the execution of TACE procedures. Two other RCTs compared lipiodol TACE versus either intravenous doxorubicin (26) or transarterial chemotherapy with zinostatin stimalamer. (27) Two additional RCTs compared lipiodol TACE with or without the addition of systemically active drugs (i.e., amiodarone in one study (28) and bevacizumab in the other (29) ).…”

Imaging Intratumoral Nanoparticle Uptake After Combining Nanoembolization with Various Ablative Therapies in Hepatic VX2 Rabbit Tumors

“…Doxorubicin has been chosen as the antineoplastic agent to be combined with the nanoparticles because it is the most active drug against HCC, producing tumor response rates of about 10–20% 28 , and is the most common drug used in chemoembolization. 29 …”

Investigating the Pretreatment miRNA Expression Patterns of Advanced Hepatocellular Carcinoma Patients in Association with Response to TACE Treatment

“…When surgery options are precluded, transarterial chemoembolization (TACE) is one of the options that can be used to treat locally advanced tumours in the liver. In this procedure, an intra-arterial injection of anticancer drugs (usually doxorubicin and/or cisplatin) is administrated immediately prior to embolization [6, 7]. Doxorubicin and cisplatin are commonly used as anticancer drugs, but their clinical efficacy is frequently limited by the development of drug resistance.…”