Hepatocellular carcinoma (HCC), which accounts for a substantial portion of cancer-related fatalities, can be managed with transcatheter arterial chemoembolization (TACE) as one of the available treatment modalities. This method, considered the standard loco-regional therapy for unresectable HCC, is hampered by issues like significant recurrence rates and liver toxicity. On the other hand, low-molecular-weight fucoidan (LMF), a sulfate polyacrylamide found in brown algae, exhibits anticancer and hepatoprotective effects.
In this blog, I would like to share the following study,” Fucoidan Improves Tumour Control and Liver Function in TACE for Unresectable Hepatocellular Carcinoma: A Randomised Trial” by Yanting Zou et al. Researchers examined if the concurrent application of LMF and TACE would lead to better therapeutic outcomes for tumors and concurrently safeguard liver function.
The analysis commenced with 82 patients who had been diagnosed with unresectable hepatocellular carcinoma (HCC), divided into an LMF group of 42 and a placebo group of 40. Baseline patient demographics and clinical characteristics, including pretreatment laboratory values, were well balanced between the two groups. All patients were classified as BCLC Stage B, and no patients were presented with major vascular invasion or extrahepatic metastasis. Baseline ALBI scores were also comparable between the two groups (LMF group: −3.41 ± 0.45 vs. placebo group: −3.53 ± 0.58; p = 0.31). It was determined that there were no statistically significant differences in any baseline characteristics, which serves to confirm that the two groups are indeed comparable for the purpose of evaluating both efficacy and safety.
First endpoint, the DCR (disease control rate), defined as the sum of CR (complete response), PR (partial response), and SD (stable disease) rates, was significantly higher in the LMF group than in the placebo group (95.24% vs. 80.00%, respectively. The reduction in progressive disease (PD) in the LMF group (4.76%) compared with the placebo group (20.00%) suggests that LMF may contribute to delaying tumor progression.
As a secondary endpoint, patients in the LMF group demonstrated a trend toward a higher objective response rate (ORR—defined as the sum of the complete response [CR] rate and the partial response [PR] rate) compared to the placebo group. However, this difference did not reach statistical significance.
During the research, neither group experienced any significant negative reactions. The incidence of adverse events, including fever, headache, nausea, vomiting, and leukemia, was comparable between the two groups, and no notable treatment-related toxicities were observed. Additionally, there were no reported instances of patients stopping treatment or passing away due to toxicity from the therapy.
In the assessment of Quality of Life (QOL), no significant differences were observed between the active treatment group and the placebo group regarding any of the evaluated domains: limitations in daily living activities, loss of appetite, constipation, sleep disturbances, anxiety, or fatigue. These results support the conclusion that the addition of LMF did not introduce new toxicities while maintaining a favorable safety profile. While the LMF group exhibited an improved disease control rate, there was no quantifiable influence on patient-reported quality of life indicators.
At baseline, all patients were classified as Child–Pugh Class A and met the eligibility criteria for enrollment in this study. Post-treatment liver function was assessed using the Child–Pugh classification at a fixed time point: six months after the initiation of LMF or placebo administration, and at least four weeks after the final TACE procedure. The purpose of this assessment was to confirm that the acute hepatic stress from treatment had resolved.
Following treatment, the proportion of patients who maintained a Child–Pugh Class A status was significantly higher in the LMF group compared to the placebo group. Conversely, the proportion of patients who progressed to Child–Pugh Class B was higher in the placebo group (35.00%) than in the LMF group (14.29%); however, progression to Class C was rare in both groups. These results suggest that LMF exerts hepatoprotective effects and may mitigate the cumulative liver injury caused by repeated TACE procedures. It is particularly important to preserve liver function in patients with unrepeatable hepatocellular carcinoma (HCC) who are undergoing loco-regional therapy, given that hepatic decompensation is a significant factor in discontinuing treatment and predicting a poor prognosis.
These results indicate that the baseline patient features were evenly distributed across both groups. The disease control rate (DCR) was significantly higher in the LMF group, while the rate of disease progression (PD rate) was lower. The objective response rate (ORR) was elevated in the LMF group; however, this increase did not reach statistical significance. LMF contributed to the preservation of liver function, with a higher proportion of patients in the LMF group maintaining Child-Pugh Class A status. The incidence of adverse events was comparable between the two groups, and no serious adverse events were observed.
To summarize, the study indicates that LMF led to enhanced control over tumors and also helped in maintaining the liver’s proper functioning, all while showing a positive and acceptable safety record. These findings indicate that LMF may be capable of reducing TACE-related liver damage and prolonging the period during which patients can continue treatment.
Source: Liver Int. 2025 Sep 17;45(10):e70347. doi: 10.1111/liv.70347