**5. Fucoidan Clinical Trials**

In general, clinical trials are used to assess if a new treatment is more e ffective and/or has less harmful side e ffects than the standard treatment. Currently, only few clinical trials have been performed to assess fucoidan in cancer. These studies tested fucoidan either as a new therapeutic agen<sup>t</sup> or as diet supplement (Table 2).



FOLFIRI: Combination chemotherapy with Irinotecan plus 5-Fuorouracil/leucovorin; FOLFOX: Combination chemotherapy with Oxaliplatin plus 5-Fuorouracil/leucovorin; NK: Natural Killer; IL-1β: Interleukin 1-β; IL-6: Interleukin 6; TNF-α: Tumor Necrosis Factor-<sup>α</sup>.

There are some examples of the use of fucoidan as a complementary therapy or food supplement in complementary alternative medicine in the treatment of cancer. A review, combining five case studies, showed clinical improvement in cancer patients, mainly using low molecular weight fucoidan supplements [93]. Other clinical trials in colorectal cancer [60] and breast cancer [89] in which fucoidans were used as a co-adjuvant treatment showed a better life quality cancer survivors [91] and in patients with advanced cancers [92]. The main fucoidan e ffects reported in cancer patients have been the improvement of negative e ffects of the chemotherapy and improved immune regulation. The fucoidan from *Cladosiphon okamuranus* for instance, decreases the cytotoxic e ffect from long-term colon cancer therapy (FOLFOX and FOLFIRI). The fucoidan in this case prevents the occurrence of fatigue during chemotherapy and increases patient survival. By ameliorating side e ffects, it enables the constant application of therapeutic drugs [90]. Fucoidan therefore has high potential for adjuvant therapy and may improve current clinical outcomes for cancer patients [55]. However, more clinical trials and further development of fucoidan applications are required.
