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CLINICAL EVIDENCE · ADVANCED HCC

HAIC FOR
ADVANCED HCC

HAIC delivers chemotherapy directly into the hepatic arterial blood supply — achieving tumour drug concentrations many times higher than systemic IV delivery, with significantly lower systemic toxicity. It is particularly valuable for advanced HCC with portal vein tumour thrombus (PVTT), where TACE alone carries high complication risk.

analyticsAt a Glance

  • check_circleHAIC-FOLFOX (oxaliplatin + fluorouracil via hepatic artery) improved OS vs sorafenib in HCC with portal vein thrombosis (PVTT) in a Chinese Phase III trial
  • check_circlePVTT (BCLC C) is the primary indication — TACE carries hepatic ischaemia risk when portal vein flow is obstructed; HAIC does not require embolisation
  • check_circleCombination HAIC + lenvatinib shows objective response rates of 40–60% — among the highest reported for any HCC combination
  • check_circleHAIC is delivered via a surgically or percutaneously implanted hepatic artery infusion port — multiple cycles over weeks to months
Reviewed by: CancerFax Medical Team, Oncology & Haematology SpecialistsLast reviewed: June 4, 2026

What Is HAIC and How Is It Different from TACE?

Both HAIC and TACE deliver drugs via the hepatic artery — but they achieve this with fundamentally different mechanisms and clinical goals. TACE combines drug delivery with arterial embolisation (blocking blood flow), inducing both direct chemotherapy cytotoxicity and ischaemic necrosis. HAIC delivers chemotherapy without embolisation — it floods the tumour and surrounding liver with high-concentration drug through intact arterial flow, without intentionally cutting off blood supply.

TACE works by cutting off the tumour's blood supply and delivering drug simultaneously. HAIC works by flooding the tumour with extraordinarily high-dose drug through its blood supply, without blocking it. The two strategies are complementary rather than competing.
  • Why HAIC Is Used When TACE Is Not Appropriate

    When the portal vein is occluded by tumour thrombus (PVTT), TACE carries a serious risk: embolising the hepatic artery in a patient whose portal vein is already blocked leaves the normal liver parenchyma without either of its two blood supplies, precipitating acute liver failure. HAIC delivers drug without embolisation — maintaining hepatic arterial flow while achieving high intrahepatic drug concentration. This makes HAIC the preferred intra-arterial approach for PVTT.

  • HAIC-FOLFOX: The Dominant Modern Protocol

    Traditional HAIC used single-agent cisplatin or fluorouracil. Modern HAIC protocols — particularly HAIC-FOLFOX (hepatic arterial infusion of oxaliplatin + fluorouracil + leucovorin, analogous to systemic FOLFOX) — have produced significantly better response rates than older single-agent protocols. HAIC-FOLFOX is now the dominant Chinese HAIC protocol and the regimen used in the pivotal Phase III trial versus sorafenib.

HAIC Clinical Evidence: Key Trial Results

HAIC-FOLFOX has been evaluated in several Chinese Phase II and Phase III trials for advanced HCC — with its most compelling evidence in the portal vein thrombosis subgroup.

HAIC-FOLFOX vs Sorafenib for HCC with PVTT — Phase III RCT (China 2021)

Source: He M et al., J Clin Oncol. 2021;39(25):2755–2764. 247 patients. Advanced HCC with portal vein tumour thrombus.

  • Median OS: HAIC-FOLFOX13.9 mo
  • Median OS: Sorafenib8.2 mo
  • ORR: HAIC-FOLFOX40.8%
  • ORR: Sorafenib2.5%

HAIC + Lenvatinib vs Lenvatinib Alone — Phase II Chinese Data

Sun Yat-sen University Cancer Center series; advanced HCC with or without PVTT

  • ORR: HAIC + Lenvatinib54.1%
  • ORR: Lenvatinib alone23.1%
  • Median PFS: HAIC + Lenvatinib10.4 mo
  • Median PFS: Lenvatinib alone6.5 mo

HAIC vs TACE: When Each Is Preferred

HAIC and TACE are complementary — each has distinct clinical strengths that guide selection based on disease characteristics.

ParameterTACE PreferredHAIC Preferred
Portal vein statusPatent portal vein — safe embolisationPortal vein tumour thrombus (PVTT) — TACE ischaemia risk is prohibitive
BCLC StageBCLC B (intermediate) — multinodular, no PVTT, no extrahepatic spreadBCLC C (advanced) with vascular invasion — TACE not guideline-standard for BCLC C
Treatment goalLocoregional control — necrosis of specific nodulesSystemic hepatic response — high-dose chemotherapy bathing multiple lesions
Tumour typeHypervascular HCC responding to arterial occlusionLess hypervascular HCC; infiltrative or perihilar HCC patterns
Prior TACE responseN/ATACE refractory — HAIC provides an alternative intra-arterial approach
Chemotherapy regimenDoxorubicin or cisplatin (bolus injection during embolisation)FOLFOX (oxaliplatin + FU + leucovorin) — infusion over 1–2 days
Systemic combinationSequential sorafenib (TACTICS); durvalumab + bevacizumab (EMERALD-1)Lenvatinib (Phase II OS benefit); sintilimab (Phase II data); emerging triplets
Hepatic arterial portNo port needed — single catheter session per procedureImplanted hepatic arterial port (HAP) required for repeated infusion cycles
AvailabilityGlobally available — any interventional radiology centreSpecialist centres primarily in China and Japan — limited availability elsewhere

HAIC-FOLFOX Protocol: Administration Details

HAIC-FOLFOX is delivered via an implanted hepatic arterial port — a catheter and subcutaneous port device placed during an angiographic procedure.

Protocol ElementDetails
Port placementInterventional radiology or surgical placement of hepatic artery catheter + subcutaneous port; typically Day 0 procedure before first cycle
FOLFOX regimen (HAIC)Oxaliplatin 85 mg/m² infused over 2 hours via HAP; leucovorin 400 mg/m² + fluorouracil 400 mg/m² bolus; then FU 2,400 mg/m² infusion over 46 hours
Cycle frequencyEvery 3 weeks — most published protocols use 3-weekly cycles for 4–6 cycles minimum
Concurrent systemic agentLenvatinib 8–12 mg daily (body weight-based) started with or after Cycle 1; sintilimab 200 mg IV q3 weeks if combination protocol
Response assessmentContrast-enhanced MRI or CT after every 2 cycles (6 weeks); AFP monitoring at each cycle; evaluate for conversion to resection if major response
Conversion surgeryIf major radiological response achieved (downstaging to resectable disease), surgical resection after 4–6 HAIC cycles may be curative — 'conversion surgery' now a recognised goal of HAIC therapy
ComplicationsCatheter occlusion/displacement (5–10%); hepatic artery thrombosis (rare); FOLFOX-related neuropathy (cumulative); port site infection (<2%)

HAIC: Key Clinical Numbers

Reference figures from the pivotal HAIC-FOLFOX trial and combination series.

  • 40.8%ORR with HAIC-FOLFOX in advanced HCC with PVTT (Phase III)Among the highest objective response rates reported for any systemic or intra-arterial therapy in BCLC C HCC with portal vein involvement.
  • 13.9 moMedian OS: HAIC-FOLFOX vs 8.2 mo sorafenib in PVTT HCCA 5.7-month median OS improvement in a population with historically very poor prognosis — establishing HAIC-FOLFOX as the preferred option for PVTT-associated advanced HCC at specialist Chinese centres.
  • 54%ORR with HAIC + Lenvatinib combinationThe highest response rate reported for any HAIC combination — supporting HAIC + lenvatinib as a potential conversion therapy pathway for selected advanced HCC patients.
  • 10–20%Conversion to resection rate with HAIC combinations in responding patientsPatients with major response to HAIC ± lenvatinib can achieve resectable disease in a meaningful proportion — making HAIC a potential bridge to curative surgery in previously unresectable cases.

Frequently Asked Questions

Common questions from patients with advanced HCC exploring HAIC.

About HAIC

  • My HCC has spread to the main portal vein — my oncologist said TACE is too risky. Is HAIC a safer option?

    Yes — HAIC is specifically designed for this situation. Main portal vein tumour thrombus (PVTT) makes TACE potentially dangerous because embolising the hepatic artery in a patient whose portal vein is already occluded can deprive the liver of both blood supplies simultaneously — precipitating acute liver failure. HAIC delivers drug through the hepatic artery without embolisation, maintaining arterial flow while flooding the tumour and liver with high-concentration chemotherapy. The Phase III trial by He et al. showed HAIC-FOLFOX achieved 40.8% objective response rates and significantly better overall survival than sorafenib specifically in patients with portal vein involvement. HAIC is most extensively available at specialist Chinese hepatology centres — CancerFax can facilitate access to programmes experienced with this specific clinical situation.

  • What does 'conversion surgery' after HAIC mean?

    Conversion surgery refers to surgical hepatic resection performed after a patient whose HCC was initially deemed unresectable achieves a major response to HAIC treatment — making the disease technically resectable. For patients with advanced HCC that responds dramatically to HAIC ± lenvatinib, the tumour may shrink to the point where a liver surgeon can remove it with clear margins. This is a potentially curative outcome in a population who started without a curative option. Conversion rates of 10–20% have been reported in HAIC responder cohorts in Chinese series. The assessment of resectability after HAIC response requires review at a hepatobiliary MDT including both an experienced liver surgeon and the HAIC interventional team — not a decision made by a single specialist.

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Exploring HAIC for Advanced HCC?

CancerFax reviews your HCC stage, portal vein status, liver function, and prior treatment to assess whether HAIC is appropriate — and connects you with specialist hepatic oncology teams in China where HAIC programmes are most extensively developed.

This content is for informational purposes only and does not constitute medical advice. Always consult a qualified oncologist before making treatment decisions.