ArticlesArterial embolisation or chemoembolisation versus symptomatic treatment in patients with unresectable hepatocellular carcinoma: a randomised controlled trial
Introduction
The incidence of hepatocellular carcinoma is increasing worldwide.1 Curative therapies, such as resection, liver transplantation, or percutaneous treatments, benefit only 25% of patients and are the only chance to improve life expectancy.2, 3, 4, 5 Despite the implementation of surveillance programmes for early hepatocellular carcinoma, most tumours are diagnosed at advanced stages, for which no standard therapy has been established.2, 3, 4, 5 Arterial embolisation induces objective responses in 16–55% of patients and lowers the rate of tumour progression. However, six randomised trials have found no survival benefits in comparisons of this therapy with or without chemotherapy (doxorubicin, cisplatin) versus conservative management or suboptimum treatments.6, 7, 8, 9, 10, 11 Similarly, two systematic reviews of some of these trials showed discrepant results.12, 13 The lack of survival benefits could be due to two factors. First, prognosis is related not only to the hepatocellular carcinoma itself, but also to the functional status of the underlying cirrhosis. Second, objective responses are not maintained with time. Accordingly, we hypothesised that very strict selection of candidates and a more aggresive retreatment schedule, aiming to prolong the initial antitumoral effect, might allow the identification of a treatment-related survival benefit and clarify the uncertainty about the usefulness of this therapy.
This sequential, multicentre, randomised controlled trial assessed the survival benefits of arterial embolisation or chemoembolisation in patients with unresectable hepatocellular carcinoma in comparison with conservative management. The three-group design would allow us to identify potential advantages from the type of embolisation applied.
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Patients
The study included consecutive white patients who met the entry criteria and agreed to participate in the trial, recruited during a 4-year period in three centres in the area of Barcelona. Hepatocellular carcinoma was diagnosed, staged, and treated according to a previously reported schedule.2 Patients with early tumours (single tumours measuring less than 5 cm or three nodules measuring less than 3 cm) are considered for radical therapies. Resection is indicated for patients with single
Results
The study began on July 1, 1996, and was stopped on July 28, 2000, when the ninth sequential inspection detected significant differences in favour of chemoembolisation. 112 (12·4%) of the 903 patients diagnosed with hepatocellular carcinoma during this time met the entry criteria and agreed to take part (figure 1). Of the 791 excluded, 310 had early hepatocellular carcinoma and underwent curative therapy (resection or liver transplantation in 154, and percutaneous treatments in 156), 68 were
Discussion
There is no standard therapy for patients with unresectable hepatocellular carcinoma.2, 3, 4, 5 Six randomised trials of arterial embolisation, with or without chemotherapy, have shown a strong antitumoral effect, but none detected survival benefits in comparison with conservative management or suboptimum treatments.6, 7, 8, 9, 10, 11 Two systematic reviews justified additional studies to define the efficacy of this technique unequivocally,12, 13 and our study offers relevant data by showing
References (22)
- et al.
Prognostic prediction and treatment strategy in hepatocellular carcinoma
Hepatology
(2002) - et al.
Treatment of hepatocellular carcinoma in patients with cirrhosis
J Hepatol
(1997) - et al.
Clinical management of hepatocellular carcinoma: conclusions of the Barcelona-2000 EASL Conference
J Hepatol
(2001) - et al.
Hepatic arterial embolization in patients with unresectable hepatocellular carcinoma: a randomized controlled trial
Gastroenterology
(1988) - et al.
A randomized trial of hepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma
J Hepatol
(1990) - et al.
Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: a multicenter randomized trial
J Hepatol
(1998) - et al.
Treatment of hepatocellular carcinoma: a systematic review of randomized controlled trials
Ann Oncol
(1997) - et al.
Epidemiology of primary liver cancer
Semin Liver Dis
(1999) - et al.
Prognosis of hepatocellular carcinoma: the BCLC staging classification
Semin Liver Dis
(1999) - et al.
Randomised trial of targeted chemotherapy with lipiodol and 5-epidoxorubicin compared with symptomatic treatment for hepatoma
Gut
(1993)
A comparison of lipiodol chemoembolization and conservative treatment for unresectable hepatocellular carcinoma
N Engl J Med
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