Esophageal

Despite being one of the less researched cancers, there are several opportunities in supplements, over the counter drugs and diet that can really improve treatment results in esophageal cancers. Surprisingly, these results are often more than can be found in some of the trials for incoming oncology drugs. Whilst often lowering serious side effects and improving all cause disease risk.

Multiple national scale studies of patient records report substantially improved outcomes in users of H1 class antihistamines. Those include desloratadine, loratadine, ebastine and others. This is attracting more research attention as evidence increases in oncology, including during immunotherapy.

Statin use has shown mixed evidence in esophageal cancer patient data, but a 2016 analysis identifies where more substantial benefits are seen; for post-diagnostic use and in adenocarcinoma variants, especially in low dose regimens. Where a prescription is lacking, red yeast rice is a good alternative. Otherwise atorvastatin and simvastatin are most frequent in clinical trials. There is less clear evidence on the benefits of vitamin D3 supplementation, but at least one study found both increases in progression free survival and improved quality of life leading to a recommendation on taking supplements.

Systemic inflammation is linked with increased risks for progression, especially in later stages. Both acute type inflammatory responses measured by C-reactive protein, and immune system related neutrophil-to-lymphocyte ratios (NLR). Maintaining relatively lower levels of both make a substantial difference. Recent studies on the benefits of chinese herbal extracts showed some significant improvements in those adding them to their oncology program. Five single herbs are called out in the report, including Astraglus and Danshen, which have entries here, and also Hedyotis diffusa (oldenlandia). Astragalus root has evidence of improving immune system balance and NLR while curcumin and other other functional foods including garlic can help bring down CRP.

In a somewhat similar theme, another recent study of microbiome diversity showed similarly large advantages in those able to maintain levels of several key gut microbiota. Several functional foods are interesting here, and in the example of oat/ egg based commercial brands there is also ongoing research relevant to most solid tumors.

The so called Th1/Th2 immune system balance is strongly linked to the progression in esophageal cancers, and to treatment resistance. Molecular iodine solutions are emerging in this area in breast cancer management, seen boosting Th1 anti tumor activity and helping suppress over active Th2 used in resistance. This has improved results in surgery plus chemotherapy and may support increased responses during immunotherapy (see Supplement Library). For immunotherapy the presence of high sodium levels is now identfied as a key marker for success in other cancers. Also in other cancers, AM treatment programs are substantially more effective that PM/evening sessions

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Antihistamines have large scale analysis of case data supporting their use in most cancers

Patient records show risk reductions of a half or more including all cause risk
Higher cumulative doses during oncology seen as giving more benefit
Other studies highlight desloratadine as overall most active H1 class anti-histamine

Our study results suggest that the incorporation of AH1 during the course of CCRT may enhance overall survival and ESCC-specific survival among patients receiving definitive CCRT for ESCC. Furthermore, our study revealed that a higher cumulative dose (cDDD) of AH1 use was associated with a decrease in all-cause mortality and ESCC-specific mortality. An optimal daily intensity of 0.84 defined daily dose (DDD) of AH1 use was identified as having the lowest ESCC-specific mortality. These findings provide evidence that the use of AH1 during CCRT may enhance outcomes for patients with ESCC

Red Yeast Rice or where possible a prescription statin have multiple beneficial actions including all-cause risks

Post-diagnostic low dose statin users with adenocarcinoma reported with improved outcomes
Esophageal adenocarcinoma specific survival rate is 44% higher, any cause mortality 36%
There were tendencies to approximately 20% improvement in other subtypes

In summary, post-diagnosis statin use was associated with large and significant reductions in EC-specific and all-cause mortality, specifically in those with EAC [adenocarcinoma. There was evidence of significant dose and cumulative dose-response relationships with prediagnosis statin use on all-cause mortality in patients with EC. These results require replication in other large cohorts and provide further evidence in support of the conduct of randomized controlled trials of statins as adjuvant agents in patients with EC.

Astragalus actions include protecting and balancing immune responses

Analysis of chinese herbal medicine in nearly 1000 stage IV cases
8% or so using mainly 4 herbal extracts halve the overall risk level
Astragalus can help re-balance ESCC immune system inflammation levels

Our study showed that CHM [chinese herbal medicine] use may be associated with a better outcome among stage IV EC [espphageal cancer] patients and could be safe when used as a part of supportive care. Besides, the core CHM and CHM combinations explored by the CMN disclosed that eliminating pathogenic factors and relieving gastrointestinal discomforts were important CHM indications. These results may warrant further clinical and bench studies for the advanced stage of EC.

Vitamin D3 and its immune system health actions are key, higher doses being trialed in oncology

Nearly 40% extended disease free survival among the 16% or so taking D3
Trend to increase overall survival in the data did not reach certainty
Relatively low dose regimes used here led to increased quality of life

In summary, we initially reported that vitamin D supplement use could enhance QOL and prolong DFS of EC. Our study supported that clinician should recommend the use of vitamin D supplementation as an intervention during cancer treatment and recovery phases to improve poor clinical outcomes. Although our results was strongly supported by previous studies, further prospective, well-designed randomized controlled trials with larger samples are necessary to further verify the impacts of vitamin D supplementation on cancer’s clinical outcomes.

Lactoferrin increases iron balance and reduces anemia rates, countering cancers use of iron

Iron deficiency here in 29% of patients, a is known to double during therapy
Dysregulated iron metabolism is a significant risk factor for progression
Maintaining healthy iron balance is reported to halve the overall risks

In our recent study, we found that anemia was identified as a highly significant prognostic factor for 2-year OS and DFS, independent of TNM stage and initial treatment in ESCC treated with primary radiotherapy. In order to investigate whether anemia would continue to affect survival, we analyzed patients between 1 January 2006 and 31 December 2007 and concluded similar results. In our current study, we found that 3-year and 5-year OS were 43% and 37%, respectively, in the non-anemic group, and 20% and 17%, respectively, in the anemic group

Oats especially functional branded foods can help increase gut health

Recent research shows higher treatment response with health gut microbiome
A large 70% increase in relative progression free survival for highly diverse microbiota
Functional foods are one opportunity to maintain levels during oncology

Strikingly, our study shows that a more stable microbial diversity despite neoadjuvant treatment is associated with a better response and PFS. Furthermore, baseline tumor and duodenal microbiota composition were related to PFS in patients treated with neoadjuvant chemoradiotherapy and atezolizumab. Future intervention studies that alter, improve or modulate the intestinal and tumor microbiome are needed to validate these results and ultimately improve treatment response.

Berberine evidence in metabolic health may help counter cancers use of lipids and sugars to grow

Female gender and non diabetics show best outcomes
Lower fasting glucose decreased risk levels by around a half
Increasing benefits for each step down in blood glucose reported

To sum up, on the basis of 2396 postoperative patients with ESCC from the FIESTA study, our findings convincingly demonstrated that the elevated preoperative fasting blood glucose can predict poor survival of ESCC patients, and this prediction was much better in males. For practical reasons, the findings of this study can help guide risk management strategies for therapeutic interventions for esophageal cancer. Pending successful validation in other independent cohorts, our findings could provide the foundation for future personalized medicine whereby ESCC patients who have elevated fasting...

Citrus Pectin removes heavy metals such as copper and has its own anti-cancer mechanisms

Promising results with copper detoxification reported in this study
Tolerability of the medical grade drugs was a limiting factor
Citrus Pectin can reduced heavy metals and has its own anti-cancer action

TM [copper detox drug] is an antiangiogenic agent that is well tolerated in the adjuvant setting. Disease-free survival and overall survival are promising when compared to historical controls treated at our institution with a similar regimen that did not include TM. However, the challenges associated with prolonged administration limit further investigation…Adjuvant tetrathiomolybdate appeared to improve the recurrence-free probability compared to historical controls although no firm conclusions can be made

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GUIDE

Pathfinder Element	Risk Reduction Factor	Anti-Metastatic	Reduces Side Effects	Research Study
Antihistamines	26 - 50%	Probably	Probably	Link
Vitamin D3	26 - 50%	Yes	Maybe	Link
Red yeast rice/ statin	26 - 50%	Probably	Maybe	Link
Astragalus	26 - 50%	Yes	Yes	Link
Gut microbiome / functional foods	Indirect - High	Probably	Yes	Link
Lactoferrin	Indirect - High	Probably	Yes	Link
Citrus Pectin	Indirect - Moderate	Probably	Yes	Link
Berberine	Indirect - Moderate	Maybe	Maybe	Link

Plan Item	Cancers	Background Details	Trial Doses Under Supervision	References
Antihistamines	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Gastric, Ovarian, Cervical, Pancreatic, Melanoma, Lymphoma, Esophageal, Bladder	Research indicates desloratadine for localized cancers or loratadine for metastatic. There are examples of ebastine or other alternatives in certain cases. Growing research evidence indicates improved oncology responses. Taken between meals. Low histamine before and during treatment is beneficial.	Active use in clinical trials is still in early phase, follow the dose recommendation for instance 5mg daily unless under medical supervision where higher 10mg doses are frequent
Aspirin	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Ovarian, Cervical, Endometrial, Pancreatic, Melanoma, Myeloma, Head and Neck, Bladder, Gallbladder, Non Melanoma Skin, Gastric	Use of low dose 75 or 81mg "baby" aspirin is reported to benefit many cancer types across an average study group, and even all cause mortality. There are some indications of specific "responders" for instance those with existing inflammatory conditions or certain gene expressions. With food.	In a colorectal cancer trial responders were tied to the expression of particular genes (PI3KA). Doses were 160mg	LINK
Astragalus	Breast, TNBC, Lung, Colorectal, Liver, Gastric, Cervical, Endometrial, Pancreatic, Prostate, Kidney, Ovarian, Glioblastoma, Non Hodgkin, Lymphoma, Leukemia, Myeloma, Head and Neck, Bladder, Gallbladder, Thyroid	A typical astraglaus membranaceus supplement may have 50mg of astragaloside IV the main active compound. Its possible with meals can reduce any stomach upset. Use of a standard dose to help immune system balance before treatment.	Here, Astragalus is added to standard oncology in lung cancer Doses are 2-3 tablets of 250mg AMe (Solgar, NJ, USA) minimum for 6 months in this example	LINK
Beta Glucans	TNBC, Lung, Liver, Gastric, Cervical, Pancreatic, Melanoma, Non Hodgkin, Lymphoma, Leukemia	There are many options for mushroom or yeast 1,3/1,6 glucan and branded products include California Gold Immune Defense/Wellmune, AHCC, Biogen/ Yestimun, ImmiFlex, IP6 and many more. A pharma grade product, odetiglucan, is continuing in trials. Take on an empty stomach. Use a standard dose to help balance the immune system before starting treatments.	AHCC is used at 3x1g per day over several months during treatment. Beta glucans are used at 1-2g per day and higher.	LINK
Danshen	Breast, Prostate, Lung, Colorectal, Liver, Leukemia, Myeloma, Bladder	The most common chinese herbal medicine in oncology, also known as red sage. Premium brands such as MCS may recommend 1g twice daily as an ongoing dose. Its possible with meals can reduce any stomach upset. Start a standard dose a couple of weeks before treatment to help balance the immune system.	3 x1g daily between meals , over at least 90 days ideally longer to get maximum benefits according to reported patient outcomes, though even shorter dose period reduced risk	LINK
Green Coffee Extract	Glioblastoma	Supplements vary in terms of their chlorogenic acid content, it can be up to 50%. Quality brand might specify this level under their recommended intake. High dose commercial brands may be over 1000mg total, take before meals.	Analysis across trials reports metabolic health benefits start are higher at >500mg or daily. High chlorogenic acid content supplements eg Svetol have been trialed safely for 12 weeks at 200mg x 5 daily dose. As always, be aware of possible drug interactions	LINK
Red Yeast Rice Or statin	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Gastric, Ovarian, Cervical, Endometrial, Melanoma, Leukemia, Myeloma, Head and Neck, Esophageal	Red yeast rice is equivalent to lovastatin. Doses are essentially on the products, and there are many premium brands with guaranteed level of monokolin k around 3mg. A common theme is findings is those with improved cholesterol are "responders". With meals. Start cholesterol and inflammation reducing statins early.	Trial data is often case studies with multiple statins where lovastatin has average effects. Often atorvastatin and sometimes simvastatin come out on top. Research ususally reports intermediate doses ( 10-20mg) are effective but there are examples indicating higher doses under supervision.	LINK
Turkey Tail	Lung, Colorectal, Kidney, Liver, Gastric	A typical premium supplement such as MCS recommend 700mg twice daily with food. Mushroom based glucans can help balance immune response so start them before your treatment.	Pharma grade turkey tail, e.g PSP/ PSK/ Krestin is typically used at 3x 1g daily during oncology, up to 36 months and more. Trials in breast cancer have also used 3,6 and 9g daily regimes in 6 week periods	LINK
Vitamin D3	Breast, TNBC, Prostate, Lung, Colorectal, Gastric, Ovarian, Pancreatic, Glioblastoma, Melanoma, Non Hodgkin, Lymphoma, Leukemia, Myeloma, Head and Neck, Esophageal, Bladder	High dose commercial formulae can be 10,000IU. Which might be achieved by as little as 10 to 20 minutes in sunshine. Vitamin K2 is advised with D3. Take with some food containing fat. Its important to ramp these up before oncology treatments, and sustain the higher levels over time. Add magnesium for best absorption and metabolism.	The VITAL trial used 2000IU and discussed the potential of higher doses to increase responders especially higher BMI/ body weight. Whilst in prostate cancer there are trials demonstrating at least 10,000IU is required to see activity reducing PSA levels	LINK
Melatonin	Breast, TNBC, Prostate, Lung, Kidney, Liver, Ovarian, Cervical, Endometrial, Pancreatic, Glioblastoma	Commonly used in 10 to 40mg daily range no reported side effects, typically an hour before sleep.	Moderate and high dose trials report no significant side effects even at 1000mg daily	LINK
Citrus Pectin	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Ovarian, Cervical, Endometrial, Pancreatic, Non Hodgkin, Leukemia, Myeloma, Head and Neck, Esophageal, Bladder, Gallbladder, Thyroid, Gastric	Trials use a recommended dose up to 5g x3 daily and no significant side effects. Taken 30 minutes before or 90 minutes after food. Ideally, start PectaClear or similar products at least 4 week before treatment to reduce heavy metals. But sustain zinc with supplementation	Even in children age 5 to 12 the daily regime 3 x 5g was safe and effective for heavy metal chelation	LINK
Soy Isoflavones	Breast, Prostate, TNBC	Often dietary sources, tofu and soy based and no evidence of side effects. Supplements generally with food.	In a clinical trial setting up to 900mg with no issues	LINK
Fermented Wheatgerm	Prostate, Colorectal, Melanoma	Trials are with Avemar brand products with no significant safety concerns reported	Typical dose regimes may be aroung 9g daily over longer time periods for instance 12 months	LINK
Iodine	Breast, TNBC	General usage around 1000mcg or 1mg generally with food	Successful pilot studies in breast cancer use 5mg molecular Iodine daily for the duration of therapy	LINK
Lactoferrin	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Gastric, Ovarian, Cervical, Endometrial, Pancreatic, Glioblastoma, Melanoma, Non Hodgkin, Lymphoma, Leukemia, Myeloma, Head and Neck, Bladder, Esophageal, Gallbladder, Thyroid	200mg typical use daily , eg 10ml liposomal formula ideally 30 minutes before meals or 2 hours after. No side effects of note. Start this immediately to achieve and maintain healthy iron absorption, avoid deficiencies and reduce cancer related ferritin levels.	During oncology doses of up to 3g to 9g daily, even higher, have been used with significant side effects	LINK
Selenium	Breast, Lung, Kidney, Ovarian, Cervical, Endometrial, Pancreatic, Melanoma, Head and Neck	Supplements are 200ug doses and similar amounts from about 3 brazil nuts. Start buildin gup your levels immediately and keep them high during oncology. Selenium toxicity is a consideration for high doses over time, so seek medical advice. Ideally taken with meals.	This trial used 2500 to 4000ug 2x daily for 14 days then once daily in kidney cancer with no dose limiting toxicity	LINK
Vitamin B3	Liver, Gastric, Glioblastoma, Non Hodgkin, Lymphoma, Leukemia, Non Melanoma Skin	Typically 500mg for nicotinamide (niacinamide) form of B3 taken ideally with meals	Do not differ from standard doses, here 500mg twice daily related to skin cancer	LINK
Akkermansia	Breast, TNBC, Prostate, Lung, Kidney, Liver, Ovarian, Cervical, Pancreatic, Non Hodgkin, Lymphoma, Leukemia, Myeloma, Head and Neck, Gastric	Commercial products may be at 10B CFU typically 30 minutes before or 2 hours after food. Ramp up levels with diet and moderate supplementation before treatments, especially immunotherapy.	Under development. Results in oncology indicate this is one of many helpful guy bacteria. careful consideration and particularly following use of antibiotics. Diversity is crucial.	LINK
Berberine	Kidney, Liver, Cervical, Pancreatic, Non Hodgkin, Leukemia, Myeloma, Head and Neck, Esophageal, Gallbladder, Thyroid, Non Melanoma Skin, Melanoma, Bladder	A natural anti-diabetic used frequently at 400mg daily and above, shortly before meals	In metabolic health trials frequentlu use up to 500mg at 3 times daily .	LINK
Curcumin	Colorectal, Liver, Non Hodgkin, Myeloma, Bladder, Gallbladder, Non Melanoma Skin, TNBC, Breast, Prostate, Lung, Kidney, Gastric, Ovarian, Cervical, Endometrial, Glioblastoma, Melanoma, Lymphoma, Leukemia, Head and Neck, Thyroid	Doses from 500mg to 2000mg frequently seen. Piperine fron black pepper improves absorption, highly bioavailable formulae are available. Ideally with a meal containing fat.	Higher doses in trials are frequently 2 of 4 g daily (+40 mg piperine) during oncology for instance here at 3 periods of 30 days	LINK
Quercetin	Glioblastoma, Myeloma	Can be found in a healty diet. Supplements often 500 or 1000mg and can be taken with tocotrienols for enhanced absorption, a form of vitamin E . Some evidence that Quercetin should be pulsed on/off.	Clincial trials have safely used up to 5g daily in adults, and 1 to 4g for rare forms of paediatric anemia	LINK
Urolithin A	Prostate, Lung, Colorectal, Kidney, Gastric, Glioblastoma, Melanoma, Myeloma, Gallbladder, Head and Neck	Typical commercial brands run at 500mg once or twice daily, with or without food, some brands suggest with meals	Trials eg in anti-aging science use the same dose range	LINK
Oat and Egg Functional Food	Breast, TNBC, Prostate, Lung, Colorectal, Kidney, Liver, Cervical, Pancreatic, Glioblastoma, Melanoma, Head and Neck, Gallbladder	Follow supplier guidance on dosage and use. https://shop.lantmannenfunctionalfoods.com/? Lowering tumor fluid pressure helps treatments work, start these before your treatment if possible. Use egg based salovum for short term "pulse" during therapy and oat products for sustained use over longer time periods	This trial in glioblastoma used 16g egg based Salovum four times daily. It discusses lowering that regime in follow on trials.	LINK
Coffee	Breast, Prostate, Colorectal, Liver, Non Melanoma Skin	Most dietary studies use standard 8oz servings as a guide. In many cases the findings are that benfits increase with intake. But in some cases such as prostate cancer there are important details in the PATHFINDER	No, but chlorogenic acid and, separately, green coffee extracts are used at 400mg and up to 2000mg
Flax	TNBC, Ovarian	Crushed flaxseed alone or in foods around 1/4 cup daily	Doses up to 50g daily in clinical trials for various diseases. Here a fairly typical 30g regime in inflammatory liver diseases	LINK
Propolis	Breast	Typical supplements range from 400 to 1000mg	Here 400mg x3 daily help recovery from radiotherapy	LINK
Walnuts	Prostate, Colorectal, Melanoma, Head and Neck	Dietary food item shown even at low useage to be helpful even at a few oz per week	Here, 2oz (56g) daily showed measurable activity in breast cancer	LINK
Mushroom	Prostate	Both dietary sources and many commercial supplements normally taken with food	In this example some patients saw responses between 8 and 14g daily of button mushroom extract	LINK
Zinc	Kidney, Ovarian, Cervical, Endometrial, Head and Neck, Non Melanoma Skin	Commercial supplements vary considerably . Moderate 20mg range generally advised	No
Intravenous HIgh Dose Vitamin C	Pancreatic, Glioblastoma	Commercial supplements vary. A moderate range around 20mg with food is generally accepted as safe.	Same as general guidance
Alpha Ketoglutarate	Melanoma, Kidney, TNBC, Non Hodgkin, Lymphoma	Typical usage is 1000mg daily with or without food, safety is good. Its especially important to ramp up and sustain your levels for maximum immunotherapy responses.	Larger doses of several grams have been safely used in various trials including here in bone disease at 6g daily	LINK
Horse Chestnut (Escin)	Thyroid	Common 300 to 600mg supplements contain 50 to 120mg of active compound, escin taken with food	Escin up to 150mg daily in vascular health. In oncology 0.6 mg/kg/day for 9 days, intravenous injection has been used, high absorption premium supplement would reacj this level	LINK

For esophageal cancers the treatment may start with chemo and/or radiotherapy and for some there can be surgical resection of tumors. Increasingly, immunotherapy drugs such as pembrlizumab (Keytruda) or nivolumab (Opdivo) may be added in the first phase, or later on following progression. In ESCC, immunotherapy has been successful in reducing overall risks by something like 20 to 40% with the higher effects in patients with high PDL-1 expression. In this group, about a third of patients, there are also significant numbers with long term robust responses https://ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.250

Your PATHFINDER brings together research that may help slow down early phase progression considerably, including reducing metastatic spread and recurrence. And, with advancing disease, maximize the effects of chemotherapy or immunotherapy. The IMPACTS tab summarizes these and can lead to Many more Good days by helping these treatments work, reducing your risk for progression and by easing treatment side effects. If you do elect both chemotherapy and immunotherapy, you can continue to look for ways to increase the results and reduce possible toxicities;

Be sure to fully read and absorb the PATHFINDER and its Impacts summary
If you have metastatic sites take a look into the corresponding Pathfinder for those too, for inspiration.
Use the Supplement Library Index and filter on “Chemotherapy” and “Immunotherapy” for ideas.
The Foods Library can complement your plan, including anti-metastatic strategies and metabolic health
In the Lifestyle section gathers fascinating evidence for diets and exercise
The PLANS section may have information from what others are doing and have learned

Esophageal

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