Chemotherapy With FOLFOX Superior to TACE in Liver Cancer

Pam Harrison

November 11, 2021

Hepatic arterial infusion chemotherapy (HAIC) with FOLFOX led to superior patient outcomes and less toxicity than standard of care transarterial chemoembolization (TACE) for patients with large, unresectable hepatocellular carcinoma (HCC), a randomized, phase 3 trial has shown.

In a group of 315 patients with unresectable tumors at least 7 cm in diameter and no macrovascular invasion or extrahepatic spread, overall survival (OS) was 42% longer at 23.1 months for patients treated with FOLFOX-HAIC, compared with 16.1 months for TACE, at a hazard ratio of 0.58 (P < .001), Ming Shi, MD, Sun Yat-sen University, Guangzhou, China, and colleagues reported recently in the Journal of Clinical Oncology.

Similarly, median progression-free survival (PFS) was also longer for FOLFOX-HAIC patients at 9.6 months, compared with 5.4 months for TACE patients, as was median symptomatic PFS at 17.9 months, compared with 10.4 months, respectively (P < .001).

The frequency of grade 3-4 elevated liver ALT at 8% versus 19% (P = .005), elevated AST at 18% versus 28%, and hyperbilirubinemia at 1% versus 6% (P = .01) were all significantly higher in the TACE group than in the FOLFOX-HAIC group as was the overall incidence of serious adverse events at 30% versus 19%, respectively (P = .03).

The frequency of treatment delay and discontinuation of TACE because of adverse events were also higher than that in the FOLFOX-HAIC group.

"Transarterial chemoembolization (TACE) is the current standard of care for intermediate-stage hepatocellular carcinoma...but the efficacy of TACE is largely dependent upon tumor size...and for patients with particularly large tumors (>7 cm), the OS after TACE is only 11.2-13.2 months," Shi and colleagues explained.

"Although the need for technical expertise may limit its generalizability, hepatic arterial infusion chemotherapy represents an appropriate frontline locoregional intervention in select patients with large unresectable hepatocellular carcinoma," they observed.


During TACE, a catheter was inserted into the celiac trunk or superior mesenteric artery for arteriography, after which a microcatheter was selectively placed into the feeding arteries of the tumors.

"Chemolipiodolization was performed using 50 mg of epirubicin and 50 mg of lobaplatin mixed with lipiodol," the investigators noted, and subsequent embolization was done with the injection of polyvinyl alcohol particles.

TACE was repeated every 6 weeks.

HAIC in turn was divided into 3-week cycles during which a microcatheter was advanced into the hepatic artery on day 1 of each treatment cycle and FOLFOX was infused via the hepatic artery. FOLFOX consisted of oxaliplatin, 130 mg/m2; leucovorin, 400 mg/m2; and fluorouracil, 400 mg/m2,
all given on day 1.

Subgroup analyses showed that HAIC provided a clinical benefit for PFS in most subgroups except females; those with a Child-Pug score of 6, and those who were negative for HBV.

The main drawback to the FOLFOX-HAIC regimen appears to be abdominal pain which some patients experienced when oxaliplatin was injected but which subsequently resolved when the injection was stopped.

As the authors pointed out, the overall response rate at 46% among patients treated with FOLFOX-HAIC was more than twice that with TACE at 18%.

"One possible reason is that FOLFOX-HAIC can provide stable local high concentrations of the chemotherapy agents in the tumor for more than 24 hours," they speculated, "whereas most chemotherapeutic agents delivered through TACE ... will be released into the systemic circulation within less than 1 hour."

Recently, drugs such as atezolizumab (Tecentriq, Roche) plus bevacizumab (Avastin, Genentech) have been shown to lead to high response rates in intermediate-stage HCC, as shown by the IMbrave 150 study.

"Therefore, in some latest practice guidelines and expert consensus statements, a switch of first-line treatment modality from TACE to systemic treatment is proposed for these patients," the researchers noted.

Limitations of the study include its open-label design and the fact that more patients in the FOLFOX-HAIC group underwent hepatic resection whereas more patients in the TACE group crossed over to the other treatment arm.

Shi declared no conflicts of interest.

This article originally appeared on, part of the Medscape Professional Network.


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