Randomised trial of targeted chemotherapy with lipiodol and 5-epidoxorubicin compared with symptomatic treatment for hepatoma.

Abstract

Lipiodol injected into the hepatic artery is selectively retained in hepatomas so has been used as a vehicle for cytotoxic drugs. This study compared treatment with 5-epidoxorubicin emulsified in lipiodol and infused into the hepatic artery with symptomatic treatment alone in a randomised trial. Of 136 patients with hepatoma 78 (57%) were not elegible, eight (6%) refused to take part, and 50 entered the trial (chemotherapy: n=25, symptomatic treatment: n=25). The two groups had similar prognostic indices. Seven of 25 patients allocated to chemotherapy were unable to receive it. The slight survival disadvantage associated with chemotherapy was not significant (median survival 48 days compared with 51 days, log rank x2=0X07, p>0.05). Patients given chemotherapy spent significantly longer in hospital, however (median three days compared with one, p=00008). Changes in symptoms and indices of tumour growth did not differ significantly between the two groups. It is concluded that infusion of 5-epidoxorubicin emulsified in lipiodol for hepatoma increased morbidity but did not affect survival. In addition, most patients were unsuitable for this treatment because of advanced disease. The patients in the trial had a short median survival time so the conclusions may not be valid for other patients with hepatoma.

Systematic review of randomized trials for unresectable hepatocellular carcinoma: Chemoembolization improves survival

“…Therefore, further studies should be published to ensure a solid assessment, mainly in reference to therapies with acceptable response rates, such as internal radiation [54][55][56] or arterial chemotherapy. [44][45][46][47][48][49][50] In summary, the present systematic review provides consistent evidence that arterial chemoembolization may benefit a subset of patients with unresectable HCC and thus proposes this therapy as the standard intervention in these cases. The data are relevant for the decision-making process of these patients, who at present do not have any option for cure.…”

“…Several treatments of unresectable HCC, such as immunotherapy with interferon, 78,80 antiandrogen therapy, 65 internal radiation, 55 and arterial 47,52 or systemic chemotherapy, 74,76 have also been evaluated in comparison with conservative management. However, none included a sufficient number of patients to guarantee a robust analysis.…”

“…Assessment of high-quality [59][60][61][62] versus low-quality trials, 57,58,63 only double-blinded, placebo-controlled studies, 59,60,62 and including all patients randomized also including tamoxifen as an adjuvant treatment of HCC. [57][58][59][60][61][62][63] and some studies published at that time are missing 28,36,43,44,46,47,50,52 whereas quasi-RCTs are included. 84 Seven new RCTs assessing embolization have been published since the first review, [30][31][32][33][41][42][43] 4 of which include an untreated control arm.…”

Chemoembolization in the Management of Liver Tumors

“…Others were unable to show a clear difference, even when compared with untreated historical controls [53]. Some randomized studies have been unable to demonstrate a significant difference in survival between patients receiving chemoembolization and those treated symptomatically [54][55][56]. However, the heterogeneity of approaches to the technique of chemoembolization-with each group using different drugs, various intervals between repeated treatments, and the presence or absence of lipiodol-makes generalization of these results impossible.…”

Intra‐arterial treatments in patients with hepatocellular carcinoma

“…In a randomized trial by Madden et al 25 no difference in tumour response or in survival was observed between patients treated with intraarterial chemotherapy mixed with Lipiodol and those treated conservatively. Ischaemia resulting from embolization is probably the main factor of tumour necrosis after TACE.…”