Transarterial chemotherapy alone versus transarterial chemoembolization for hepatocellular carcinoma: A randomized phase III trial

doi:10.1016/j.jhep.2009.09.004

Journal of Hepatology

Volume 51, Issue 6, December 2009, Pages 1030-1036

https://doi.org/10.1016/j.jhep.2009.09.004 Get rights and content

Background/Aims

Transcatheter arterial chemoembolization (TACE) is a combination of transarterial infusion chemotherapy (TAI) and embolization, and has been widely used to treat patients with hepatocellular carcinoma (HCC). However, since the impact of adding embolization on the survival of patients treated with TAI had never been evaluated in a phase III study, we conducted a multi-center, open-label trial comparing TACE and TAI to assess the effect of adding embolization on survival.

Methods

Patients with newly diagnosed unresectable HCC were randomly assigned to either a TACE group or a TAI group. Zinostatin stimalamer was injected into the hepatic artery, together with gelatin sponge in the TACE group and without gelatin sponge in the TAI group. Treatment was repeated when follow-up computed tomography showed the appearance of new lesions in the liver or re-growth of previously treated tumors.

Results

Seventy-nine patients were assigned to the TACE group, and 82 were assigned to the TAI group. The two groups were comparable with respect to their baseline characteristics. At the time of the analysis, 51 patients in the TACE group and 58 in the TAI group had died. The median overall survival time was 646 days in the TACE group and 679 days in the TAI group (p = 0.383).

Conclusions

The results of this study suggest that treatment intensification by adding embolization did not increase survival over TAI with zinostatin stimalamer alone in patients with HCC.

Section snippets

1. Introduction

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and a major cause of cancer mortality [1]. Although the screening of populations with a high risk of HCC using ultrasonography and serum α-fetoprotein (AFP) measurements have recently increased the number of candidates for effective local treatments such as hepatic resection and local ablation therapy, many patients exhibit HCCs that are unsuitable for local treatments at the time of the initial diagnosis or at the time

2. Methods

Consecutive new patients with HCC were eligible if they had no indications for resection and/or local ablation therapy. The diagnosis was confirmed histologically and/or clinically using angiography and computed tomography (CT). Each patient was required to meet the following criteria: intrahepatic lesions that showed tumor staining by angiography and those in which the total size was less than 50% of the entire liver; adequate hematological function (white blood cells ⩾3000/mm³, platelets

3. Results

Between October 1999 and June 2003, 222 patients were provisionally enrolled in the study at 10 Japanese centers (Fig 1). Sixty-one of the 222 patients were excluded because of ineligibility for intra-arterial treatment based on the angiographic findings or withdrawal of consent; too few or too many definitive tumors that required reconsideration of the treatment strategy (46), tumor thrombus in the portal vein (3), tumors without sufficient tumor staining (3), intrahepatic arteriovenous

4. Discussion

We initiated this randomized study in 1999 because the impact of adding embolization on overall survival for patients with advanced HCC treated with TAI had not been fully evaluated and because the efficacy of TACE was still being debated at that time in various countries. Moreover, several differences in TACE methods had been noted between clinical practice in East Asian countries, including Japan, and randomized studies conducted in Europe, including differences in the selection of

Acknowledgments

This study was presented in part at the 43rd Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 1–5, 2007.

This study was supported by a Grant-in-Aid for Cancer Research (Grant No. 11-15) from the Ministry of Health, Labour, and Welfare of Japan. This article is dedicated to the memory of the late Dr. S. Okada, a principal investigator. We thank Ms. K. Kondo for her assistance in the data collection and preparation of the manuscript.

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^☆: The authors who have taken part in this trial do not have a relationship with the manufacturers of the drugs involved either in the past or present and did not receive funding from the manufacturers to carry out their research. This study was supported by a Grant-in-Aid for Cancer Research (Grant No. 11-15) from the Ministry of Health, Labour and Welfare of Japan. Trial registration: UMIN C000000111.

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Transarterial chemotherapy alone versus transarterial chemoembolization for hepatocellular carcinoma: A randomized phase III trial☆

Background/Aims

Methods

Results

Conclusions

Section snippets

1. Introduction

2. Methods

3. Results

4. Discussion

Acknowledgments

Clin Liver Dis

Gastroenterology

J Hepatol

J Hepatol

Hepatology

Lancet

Hepatology

Eur J Cancer Clin Oncol

Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: results of a randomized, controlled trial in a single institution

Hepatology

Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials

Radiology

Transarterial chemotherapy with zinostatin stimalamer for hepatocellular carcinoma

Oncology