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Tumeric Prevents Chemotherapy Induced Hand Foot Syndrome

Xeloda (Capecitabine) is the oral form of  chemotherapy agent 5-Fluorouracil  (5-FU) which is administered intravenously. 

Both drugs are widely used in a broad range of cancers. The mechanism of action is inhibition of mitosis (cell division).   

One of the most common side effects of these drugs is HAND-FOOT SYNDROME or palmar-plantar erythrodysesthesia.  Hand-Foot syndrome presents with redness, swelling and pain, tingling, burning and sensitivity to touch on the palms of the hands and the soles of the feet. Severe cases may include cracked, flaking or peeling skin, painful blisters, ulcers or sores, severe pain and difficulty walking or using the hands.

While etiology is not certain it is hypothesized that these drugs cause capillary fragility and subsequent leakage of drugs into and damage of  the surrounding tissue.

fhs

Other commonly used chemotherapy agents  which result in Hand - Foot syndrome include 5-Fluorouracil, Capecitabine, Cytarabine, Docetaxel, Doxorubicin, Doxil and Paclitaxel. These drugs are widely used in Breast, Ovarian and Gastrointestinal Cancers.  

Not all patients who receive these drugs develop Hand-Foot Syndrome. The symptoms typically appear with the first dose administration in 40-50 percent of patients at grade 2 or higher.

turmeric-as-cure

Grade 1: painless erythema or dysesthesia, no impairment

Grade 2: painful erythema, swelling, tingling, numbness, dryness, cracking, Desquamation, activity is impaired

Grade 3: strong pain, ulceration, blistering, erythema, limited self-sufficiency

For drugs administered via IV infusion, cold (Ice) gloves and booties that constrict capillaries reduce local exposures in the hands and feet and must be worn during infusions and for several therapy to hands and feet concurrently with chemotherapy infusions. 

Capcetabine increases COX-2 expression in both tumors and healthy tissues.

A double blind placebo controlled study in which oral COX2 inhibitor celecoxib was administered to patients over a 2 year period while receiving capecitabine or capecitabine plus oxaliplatin demonstrated a significant decrease in the incidence and intensity of symptoms.

The phytochemical curcumin derived from Rhizoma Curcuma longa interacts with over 100 genes that impact tumor cell behavior and metabolism. Curcumin is known to decrease COX2 expression along with expression of  pro-inflammatory NFkB, TNFa, IL1B, IL6 and IL8.  

foot-hand-syndromeIn a human study researchers administered turmeric at a dose of 4 g/day (2 pills 12 hours apart) starting at the beginning of capecitabine treatment and lasting six weeks. The study included 40 patients whose mean age was 62 years. Most were female (80%), 52% had breast cancer, and 47.5% had GI tumors. After the first cycle of capecitabine treatment, 11 of 40 patients developed HFS (27.5%; 95% CI [15, 42]), whereas four patients developed HFS equal or superior to grade 2 (10%; 95% CI [3.3, 23]).. The study concluded that  turmeric combined with capecitabine seems to produce a lower rate of HFS, especially grade 2 or higher. 

Comments

  • There were no contra-indications to utilizing turmeric concurrently with capecitabine
  • A significant therapeutic dose of 4 grams per day was used.   In my practice I prefer to use the more concentrated isolate curcumin and dose at 2-4 grams per day.  This would yield more inflammation control.   
  • Turmeric falls into the category of herbs that “Move Stagnant Blood” in Chinese Medicine.  One of the properties of curcumin is inhibition of platelet aggregation.

References:

Curcuma longa (Turmeric) for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Pilot Study

Vanessa Armenio Scontre , MD,Janine Capobiango Martins , MD, et al 

Jnl Diet Supp Pages 606-612 | Published online: 02 Nov 2017

 https://doi.org/10.1080/19390211.2017.1366387 PMID: 2909565

The effect of COX-2 inhibitor on capecitabine-induced hand-foot syndrome in patients with stage II/III colorectal cancer: a phase II randomized prospective study.Zhang RX, Wu XJ, Lu SX, Pan ZZ, Wan DS, Chen G.
J Cancer Res Clin Oncol. 2011 Jun;137(6):953-7. doi: 10.1007/s00432-010-0958-9. Epub 2010 Nov 27.
PMID: 21113620 Clinical Trial.

Clinical Pearl-cancer

Clinical Pearl: Chemotherapy Reduces Magnesium to Dangerously Low Levels

 

Hypomagnesia occurs in 29-100% of cancer patients receiving chemotherapy.

Magnesium deficiency is common in cancer patients, especially those receiving chemotherapy.  Magnesium is the second most abundant intracellular cation after potassium. It is involved in >600 enzymatic reactions in the body.

Hypomagnesia induces  fatigue , mitochondropathy (compromised mitochondrial function )and risk for neuropathy, nephropathy as well as abnormal cardiovascular function (arrhythmia, hypertension) immune dysfunction, headache and altered bone and Vitamin D metabolism.  Hypomagnesia is associated with nausea, vomiting, headache, myalgia, constipation, anxiety, insomnia and depression, all common complaints of cancer patients.

Long term and extreme hypomagnesia promotes cancer treatment related fatigue, cortical blindness, insulin resistance, prolonged QT interval, hypertension, seizures, tremor, psychiatric disturbances, migraine headaches and is associated with chronic inflammation and oxidative stress.

Magnesium status declines with age.

As cancer patients are typically over 50 years old, hypomagnesia may be present long before diagnosis. Pre-menopausal women and athletes also have higher needs of magnesium and may be deficient. 

This may influence the tumor microenvironment towards carcinogenesis, tumorogenesis, proliferation and progression.

Both oral and intravenous repletion relieve many of the hypomagnesia related adverse effects.

Adverse effects can be prevented by supplementing with magnesium in advance of as well as after chemotherapy. In a health model, keep patients replete with Magnesium at times to optimize function, prevent deficiency syndromes and adverse symptoms of chemotherapy.

Monitoring and Management of Magnesium Status

All patient care plans include oral Magnesium Glycinate Chelate

Daily Dose: 600-900mg daily in capsule, liquid or powder form

(Glycinate and Bis-Glycinate chelates are more well absorbed and less likely to have a laxative effect than other forms of magnesium chelate). Excess oral magnesium can lead to diarrhea. Spread out oral dosing over 3-4 doses per day to achieve repletion without loose stool.

Extreme Hypomagnesia can be quickly repleted by intravenous infusion.

All patients are monitored for Serum RBC Magnesium to assess magnesium status every 3-6 months long-term and monthly during active chemotherapy.

Serum Magnesium is not a reliable indicator of Magnesium deficiency.

 

Dietary Sources of Magnesium include:

Almonds, cashews, brazil nuts, pumpkin seeds, flaxseeds, cocoa, avocados, dark leafy greens, seaweed

 

Chemotherapeutic agents that induce hypomagnesia:

Platinum Chemotherapy Agents : Oxaliplatin, Cisplatin, Carboplatin and

Taxanes:  paclitaxel (Taxol) nab-paclitaxel (Abraxane), docetaxel (Taxotere),Cabazitaxel (Jevtana).

Vinca alkaloids vinblastine, vincristine, vindesine, and vinorelbine.