A new randomized controlled trial has found that low-molecular-weight fucoidan (LMF) may help improve quality of life and reduce certain side effects in patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy. The study, published in June 2023 in Integrative Cancer Therapies, is the first prospective, double-blind, placebo-controlled trial to evaluate LMF as a supplemental therapy in this patient population.
The research was conducted at Kaohsiung Medical University Hospital in Taiwan and funded by grants from the Ministry of Science and Technology, Ministry of Health and Welfare, and Kaohsiung Medical University Hospital. Additional support was provided by the Taiwan Precision Medicine Initiative and Taiwan Biobank.
The purpose of the study was to investigate the effects of LMF supplementation on quality of life, clinical outcomes, and gut microbiota in patients with locally advanced rectal cancer receiving neoadjuvant concurrent chemoradiotherapy (CCRT) before surgery. Neoadjuvant CCRT is the standard treatment for locally advanced rectal cancer but can cause significant side effects that impact quality of life.
A total of 87 patients were included in the final analysis - 44 in the fucoidan group and 43 in the placebo group. Eligible patients were aged 20-80 years with locally advanced rectal cancer confirmed by pathology or radiology, had an ECOG performance status of 0-2, and a life expectancy of at least 4 months. Exclusion criteria included major underlying diseases, other malignancies, inability to tolerate standard chemoradiotherapy, and loss to follow-up within 1 year.
The study design was a prospective, randomized, double-blind, placebo-controlled trial. Patients were randomly assigned 1:1 to receive either 4 g of LMF powder or 4 g of cellulose powder (placebo) twice daily for 3 months during their neoadjuvant CCRT treatment. The LMF was derived from the brown seaweed Sargassum hemiphyllum and had an average molecular weight of 0.8 kDa.
Baseline characteristics were similar between the two groups. The median age was 65 years in the fucoidan group and 62 years in the placebo group. Approximately 57% of fucoidan patients and 65% of placebo patients were male.
The primary endpoint was quality of life as measured by the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) questionnaire. This validated tool assesses physical, social/family, emotional, and functional well-being, as well as additional colorectal cancer-specific concerns.
Results showed that patients in the fucoidan group had significantly better physical well-being scores at 2 months (23.36 vs 21.18, p=0.007) and 3 months (23.27 vs 21.12, p=0.006) post-treatment compared to the placebo group. However, there were no statistically significant differences in overall FACT-C scores or other subscales between the groups.
In terms of adverse events, patients taking fucoidan experienced significantly less skin rash/itching (0% vs 9.3%, p=0.038) and fatigue (75% vs 95.3%, p=0.008) compared to placebo. There were no significant differences in rates of severe adverse events between the groups.
The study also examined clinical outcomes, including disease-free survival (DFS) and overall survival (OS). While not statistically significant, there were trends toward improved survival in the fucoidan group. The 2-year DFS rate was 86% in the fucoidan group vs 76% in the placebo group. The 2-year OS rate was 100% vs 91%, respectively.
An analysis of gut microbiota showed that levels of bacteria in the genus Parabacteroides were significantly higher in the fucoidan group post-treatment (p=0.015). Previous research has suggested Parabacteroides may have beneficial effects in colorectal cancer.
The authors concluded that LMF supplementation during neoadjuvant CCRT for locally advanced rectal cancer may help improve physical well-being, reduce certain side effects like fatigue and skin issues, and potentially alter the gut microbiome in beneficial ways. However, they noted several limitations of the study.
Key limitations included the relatively small sample size of 87 patients and insufficient follow-up time to fully evaluate long-term survival outcomes. Additionally, some patients were excluded from analysis due to non-completion of the full CCRT regimen or loss to follow-up within 1 year.
The researchers stated that larger studies with longer follow-up are needed to confirm the potential benefits of LMF supplementation in this patient population. They also suggested further research to elucidate the mechanisms by which fucoidan may impact quality of life, side effects, and clinical outcomes.
If confirmed in larger trials, these findings could have several potential clinical impacts. LMF supplementation during neoadjuvant CCRT for rectal cancer may offer a relatively simple way to help maintain patients' physical well-being and reduce bothersome side effects like fatigue and skin reactions. This could potentially lead to better treatment adherence and outcomes.
The trends toward improved survival, while not statistically significant in this study, are also intriguing and warrant further investigation. If a survival benefit is shown in larger studies, it could provide justification for more widespread use of LMF as an adjunct therapy in this setting.
The observed changes in gut microbiota composition with LMF supplementation may also have clinical relevance. Emerging research suggests the gut microbiome can impact cancer treatment efficacy and side effects. Modulation of the microbiome through LMF or other means could potentially become a strategy to optimize treatment outcomes.
It's important to note that while this study used a specific LMF product derived from Sargassum hemiphyllum seaweed, different fucoidan products may vary in their composition and effects. More research is needed to determine optimal dosing and formulations.
Additionally, the generalizability of these findings to other patient populations and cancer types remains to be determined. The study focused specifically on patients with locally advanced rectal cancer undergoing neoadjuvant CCRT. Whether similar benefits would be seen in other gastrointestinal cancers or treatment settings is unknown.
This study adds to a growing body of research on the potential anticancer and supportive care applications of fucoidan, a sulfated polysaccharide found in brown seaweeds. Previous in vitro and animal studies have suggested fucoidan may have antitumor, immunomodulatory, and anti-inflammatory properties.
While fucoidan products are already widely used as dietary supplements, particularly in Asia, this is one of the first rigorous clinical trials to evaluate its effects as an adjunct to standard cancer therapy. The double-blind, placebo-controlled design helps address limitations of previous observational studies and provides higher quality evidence.
The focus on patient-reported outcomes like quality of life is also notable. As cancer treatments continue to improve survival for many patients, there is increasing emphasis on maintaining quality of life during treatment. Interventions that can help reduce treatment-related side effects and maintain physical functioning are of great interest.
At the same time, the lack of significant differences in overall quality of life scores between groups highlights the complexity of assessing these outcomes. It's possible the FACT-C instrument was not sensitive enough to capture all relevant effects, or that a larger sample size was needed to detect differences.
The potential for LMF to modulate the gut microbiome is an intriguing finding that fits with the growing recognition of the microbiome's importance in health and disease. However, the clinical significance of the specific changes observed in this study remains to be determined. More research is needed to understand the functional impacts of these microbial shifts.
In conclusion, this well-designed randomized trial provides preliminary evidence that LMF supplementation may offer some benefits for patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiotherapy. While not a magic bullet, it appears to be a safe intervention that could potentially help maintain physical well-being and reduce certain side effects during a challenging treatment regimen.
Larger studies are now needed to confirm these findings and further evaluate potential impacts on long-term clinical outcomes. If benefits are confirmed, LMF could become a valuable supportive care option for this patient population. More broadly, this study highlights the potential for evidence-based integration of natural products into conventional cancer care paradigms.
References
Tsai HL, Yeh YS, Chen PJ, et al. The Auxiliary Effects of Low-Molecular-Weight Fucoidan in Locally Advanced Rectal Cancer Patients Receiving Neoadjuvant Concurrent Chemoradiotherapy Before Surgery: A Double-Blind, Randomized, Placebo-Controlled Study. Integr Cancer Ther. 2023;22:15347354231187153. doi:10.1177/15347354231187153
