Efficacy of hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma

Abstract

Aim: To investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) using floxuridine (FUDR) in patients with advanced hepatocellular carcinoma (HCC) confined to the liver.

Methods: Thirty-four patients who had advanced HCC with unresectability or unsuccessful previous therapy in the absence of extrahepatic metastasis were treated with intra-arterial FUDR chemotherapy at our hospital between March 2005 and May 2008. Among the 34 patients, 9 patients were classified as Child class C, and 18 patients had portal vein tumor thrombus (PVTT). One course of chemotherapy consisted of continuous infusion of FUDR (0.3 mg/kg during day 1-14) and dexamethasone (10 mg on day 1, 4, 7 and 11), and this treatment was repeated every 28 d.

Results: Two patients (5.9%) displayed a complete response, and 12 patients (35.3%) had a partial response. The tumor control rate was 61.8%. The median overall survival times were 15.3 mo, 12.4 mo and 4.3 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0392). The progression-free survival was 12.9 mo, 7.7 mo and 2.6 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0443). The cumulative survival differed significantly according to the Child-Pugh classification and the presence of PVTT. In addition to hepatic reserve capacity and PVTT, the extent of HCC was an independent factor in determining a poor prognosis. The most common adverse reactions to HAIC were mucositis, diarrhea and peptic ulcer disease, but most of these complications were improved by medical treatment and/or a delay of HAIC.

Conclusion: The present study demonstrates that intra-arterial FUDR chemotherapy is a safe and effective treatment for advanced HCC that is recalcitrant to other therapeutic modalities, even in patients with advanced cirrhosis.

Keywords: Advanced hepatocellular carcinoma; Child-Pugh classification; Floxuridine; Hepatic arterial infusion chemotherapy; Portal vein tumor thrombus.

Figure 1

Two cases of nearly complete response. A: The first case was a 54-year-old patient with diffuse, multinodular hepatocellular carcinoma throughout the whole liver. After 9 cycles of hepatic arterial infusion chemotherapy (HAIC) with floxuridine, no enhancing nodular lesions were observed by dynamic contrast-enhanced computed tomography (CT); B: The second case was a 48-year-old patient with a large mass in the left lobe and intrahepatic metastasis in the right lobe. After transarterial chemoembolization treatment, viable masses were still observed in sequential CT images, and HAIC was started. After 8 cycles of chemotherapy, no viable masses were observed. TACE: Transarterial chemo-embolisation.

Figure 2

The overall survival and the progression-free survival determined by Kaplan-Meier analysis. A: The overall survival (OS) determined by Kaplan-Meier analysis; B: The progression-free survival (PFS) determined by Kaplan-Meier analysis.

Figure 3

Kaplan Meier plot estimates of the overall survival and the progression-free survival according to the Child-Pugh classification and existence of portal vein tumor thrombus. A: Kaplan Meier plot estimates of the overall survival (OS) to the Child-Pugh classification; B: Kaplan Meier plot estimates of the progression-free survival (PFS) according to the Child-Pugh classification; C: Kaplan Meier plot estimates of the OS according to existence of portal vein tumor thrombus (PVTT); D: Kaplan Meier plot estimates of the PFS according to existence of PVTT.