Amazing research from Japan regarding Fucoidan supplementation in complement with traditional cancer therapies like Cisplatin. In this study, Twenty-four (24) patients with unresectable advanced gastric cancer underwent treatment with S-1 plus cisplatin and were randomly allocated into afucoidan treatment group (n = 12) or a control group without fucoidan treatment (n = 12). In Japan, S-1 plus cisplatin has become a standard regimen for the treatment of unresectable advancedgastric cancer; however, many patients are unable to continue effective chemotherapy becauseof the regimen’s severe side effects (1).
The synonym "S-1" refers a foreign brand name, Teysuno®. It is comprised of tegafur-gimeracil-oteracil potassium - An orally bioavailable fluoropyrimidine antagonist composed of tegafur combined with two modulators of 5-flurouracil (5-FU) activity, 5-chloro-2,4-dihydroxypyridine (CDHP) and potassium oxonate. Essentially it regulates key protein sythesis and enzymes, aiding in cancer cell destruction in your gut. And sure, there are a few Scrabble word winners in here, too.
Cisplatin — short for cis -platinum — was a new drug forged out of an old one. Its molecular structure, a central planar platinum atom with four "arms" extending outward, had been described back in the 1890s. A beautiful compound that no one knew what do to with it. We want our readers to know Cisplatin well, not only for this blog article, but for our others that speak to this compound that has such a colored history. Candidly, no one tells the story better than Siddhartha Mukherjee, MD, Phd, in his book, "The Emperor of All Maladies: A Biography of Cancer;"
"... but chemists had never found an application for cisplatin: the beautiful, satisfyingly symmetric chemical structure had no obvious human use. It had been shelved away in the laboratory in relative obscurity. No one had bothered to test its biological effects. In 1965, at Michigan State University, a biophysicist, Barnett Rosenberg, began to investigate whether electrical currents might stimulate bacterial cell division. Rosenberg devised a bacterial flask through which an electrical current could be run using two platinum electrodes. When Rosenberg turned the electricity on, he found, astonishingly, that the bacterial cells stopped dividing entirely. Rosenberg initially proposed that the electrical current was the active agent in inhibiting cell division. But the electricity, he soon determined, was merely a bystander. The platinum electrode had reacted with the salt in the bacterial solution to generate a new growth-arresting molecule that had diffused throughout the liquid. That chemical was cisplatin. Like all cells, bacteria need to replicate DNA in order to divide. Cisplatin had chemically attacked DNA with its reactive molecular arms, cross-linking and damaging the molecule irreparably, forcing cells to arrest their division. 000 For patients such as John Cleland, cisplatin came to epitomize the new breed of aggressive chemotherapeutics of the 1970s. In 1973, Cleland was a twenty-two-year-old veterinary student in Indiana. In August that year, two months after his marriage, he discovered a rapidly expanding lump in his right testis. He saw a urologist on a Tuesday afternoon in November. On Thursday, he was whisked off to the operating room for surgery. He returned with a scar that extended from his abdomen to his breastbone. The diagnosis was metastatic testicular cancer — cancer of the testes that had migrated diffusely into his lymph nodes and lungs. In 1973, the survival rate from metastatic testes cancer was less than 5 percent. Cleland entered the cancer ward at Indiana University and began treatment with a young oncologist named Larry Einhorn. The regimen, a weather-beaten and toxic three-drug cocktail called ABO that had been derived from the NCI's studies in the 1960s — was only marginally effective. Cleland lived in and out of the hospital. His weight shrank from 158 to 106 pounds. One day in 1974, while he was still receiving chemo, his wife suggested that they sit outside to enjoy the afternoon. Cleland realized, to his utter shame, that he was too weak to stand up. He was carried to his bed like a baby, weeping with embarrassment. In the fall of 1974, the ABO regimen was stopped. He was switched to another equally ineffective drug. Einhorn suggested a last-ditch effort: a new chemical called cisplatin. Other researchers had seen some responses in patients with testicular cancer treated with single-agent cisplatin, although not durable ones. Einhorn wanted to combine cisplatin with two other drugs to see if he could increase the response rate. There was the uncertainty of a new combination and the certainty of death. On October 7, 1974, Cleland took the gamble: he enrolled as "patient zero" for BVP, the acronym for a new regimen containing bleomycin, vinblastine, and cisplatin (abbreviated P for "platinum"). Ten days later, when he returned for his routine scans, the tumors in his lungs had vanished. Ecstatic and mystified, he called his wife from a hospital phone. "I cannot remember what I said, but I told her." Cleland's experience was typical. By 1975, Einhorn had treated twenty additional patients with the regimen and found dramatic and sustained responses virtually unheard of in the history of this disease. Einhorn presented his data at the annual meeting of oncologists held in Toronto in the winter of 1975. "Walking up to that podium was like my own walk on the moon," he recalled. By the late winter of 1976, it was becoming progressively clearer that some of these patients would not relapse at all. Einhorn had cured a solid cancer by chemotherapy. 'It was unforgettable. In my own naive mind I thought this was the formula that we had been missing all the while.' Cisplatin was unforgettable in more than one sense. The drug provoked an unremitting nausea, a queasiness of such penetrating force and quality that had rarely been encountered in the history of medicine: on average, patients treated with the drug vomited twelve times a day. (In the 1970s, there were few effective antinausea drugs."
Hopefully, readers are reading this ... by this point, the "scrolling" response of OMG this article is long would detract the fluff readers ... but not you, you are here at this point in the paragraph because you are genuinely interested in solving this problem ... it would be most important to understand the history of cancer and chemotherapy to be able to innovate for the future ...
"Most patients had to be given intravenous fluids to tide them through the nausea; some survived by smuggling marijuana, a mild antiemetic, into the chemotherapy wards.) In Margaret Edson's play Wit, a scathing depiction of a woman's battle with ovarian cancer, an English professor undergoing chemotherapy clutches a nausea basin on the floor of her hospital ward, dry-heaving in guttural agony (prompting her unforgettable aside, "You may think my vocabulary has taken a turn for the Anglo-Saxon"). The pharmacological culprit lurking unmentioned behind that scene is cisplatin. Even today, nurses on oncology floors who tended to patients in the early 1980s (before the advent of newer antiemetics that would somewhat ease the effect of the drug) can vividly recollect the violent jolts of nausea that suddenly descended on patients and brought them dry-heaving to the ground. In nursing slang, the drug came to be known as "cisflatten." These side effects, however revolting, were considered minor dues to pay for an otherwise miraculous drug. Cisplatin was touted as the epic chemotherapeutic product of the late 1970s, the quintessential example of how curing cancer involved pushing patients nearly to the brink of death. By 1978, cisplatin-based chemotherapy was the new vogue in cancer pharmacology; every conceivable combination was being tested on thousands of patients across America. The lemon- yellow chemical dripping through intravenous lines was as ubiquitous in the cancer wards as the patients clutching their nausea basins afterward."
As cancer is essentially the study of life, life adapts. The researchers had to adapt as well. The story is telling as it starts out with small numbers of patients and builds up. This research article is the beginning of a new story.
Not every cancer was responding to Cisplatin as they had in the past. It, the cancer, has adapted and some are resistant. Therefore, we add more like "S-1" in addition to Cisplatin - in hopes to curb cancer in multiple pathways.
We find ourselves at an interesting inflection point in this research. As many know, our Infinitum Health products are based on a "Multiple Pathway Hypothesis" as well, and focus our formulations using natural products only. The use of blends of synthetic chemotherapeutic drugs is interesting as it brings us back to Traditional Chinese Medicine practices and the ability to add different ingredients to optimize the effect.
From the original study, Fucoidan, from seaweed was added to the blend, including S-1 and Cisplatin. It was added, largely as it has a proven ability to manage toxic effects of chemotherapy and oh, by the way, also has anticancer properties. We have seen this in so many of the research studies posted on our site as well as Pubmed, where fucoidan has skyrocketed in the past decade in terms of number of research articles published.
One of the key reasons people die during chemotherapy is due to its toxicity. Thus, control of drug toxicity is key to prolonging patient survival.
The study results demonstrated that fucoidan controlled the occurrence of fatigue during chemotherapy and patients could continue chemotherapy for longer time periods by maintaining the patients’ favorable nourishment status. As a result, the survival of patients with fucoidan treatment was longer than that of patients without fucoidan.
The patient's prognostic nutritional indices (PNIs) of all 24 patients at 3 months after commencing chemotherapy (post-treatment) were compared with those of the patients before treatment (pre-treatment). The PNIs of post-treatment were similar to those pre-treatment. The results also indicate that the PNI increased at post-treatment compared with pre-treatment for 14 patients (eight: fucoidan group and six: control group). Correlation between fucoidan treatment, chemotherapy, and PNI is indicated in Table 3 of the study (below).
The mean survival time (MST) of the 14 patients with increased PNI at post-treatment (11 months) was significantly better than that of 10 patients with decreased PNI post-treatment (6 months, P = 0.006). Broadly for all patients in the study, a statistically significant difference was made in MST for patients supplemented with fucoidan (P = 0.039) as shown in Figure 1 of the study.
These results indicate that fucoidan may prevent the deterioration of patients’ PNI due to chemotherapy.
Recent research reported that fucoidan is also able to suppress in vitro tumor progression. Yamasaki-Miyamoto et al. (3) and Hyun et al. (4) have demonstrated that fucoidan activates caspase-8 or extracellular signalregulated kinase and induced apoptosis in tumor cells. The pro-apoptotic effects of fucoidan have been shown in a gastric cancer cell line (5).
In the present study, even though the number of patients was small, the prognosis of patients with unresectable advanced gastric cancer was better with fucoidan treatment compared with those patients not supplemented with fucoidan. One reason could be that fucoidan prolonged chemotherapy duration by suppressing the toxicity of the chemotherapy drugs. Another reason might be an anticancer effect of fucoidan itself.
Thus, concluded by the authors of the study, fucoidan should be included as a key food supplement for patients with gastrointestinal carcinomas who are suffering from the adverse side effects of chemotherapy, but highlights the need for larger controlled studies to evaluate the therapeutic effect of fucoidan for patients with gastrointestinal carcinoma.
We would echo that more research is needed, but amazing start to clinical trial work in humans!
1. Ikeguchi, M., Saito, H., Miki, Y. and Kimura, T. (2015) Effect of Fucoidan Dietary Supplement on theChemotherapy Treatment of Patients with Unresectable Advanced Gastric Cancer. Journal of Cancer Therapy, 6, 1020-1026.http://dx.doi.org/10.4236/jct.2015.611111
2. Siddhartha Mukherjee. The Emperor of All Maladies: A Biography of Cancer. August, 2011.
3. Yamasaki-Miyamoto, Y., Yamasaki, M., Tachibana, H. and Yamada, K. (2009) Fucoidan Induces Apoptosis throughActivation of Caspase-8 on Human Breast Cancer MCF-7 Cells. Journal of Agricultural and Food Chemistry, 57,8677-8682. http://dx.doi.org/10.1021/jf9010406
4. Hyun, J.H., Kim, S.C., Kang, J.I., Kim, M.K., Boo, H.J., Kwon, J.M., Koh, Y.S., Hyun, J.W., Park, D.B., Yoo, E.S.and Kang, H.K. (2009) Apoptosis Inducing Activity Of fucoidan in HCT-15 Colon Carcinoma Cells. Biological &Pharmaceutical Bulletin, 32, 1760-1764. http://dx.doi.org/10.1248/bpb.32.1760
5. Yoshimoto, M., Higaki, K., Nanba, E. and Ikeguchi, M. (2015) Anti-Proliferation Activity of Fucoidan in MKN45Gastric Cancer Cells and Downregulation of Phosphorylated ASK1, a Cell Cycle-Regulated Kinase. Yonago Acta Medica,58, 1-7.