Therapies For Chemo-Related And Other Neuropathies

Today's post from (see link below) is a very comprehensive and informative article about neuropathy as a result of chemotherapy treatment. That said, almost all the information here applies to treatments for other forms of neuropathy too and the various treatment options apply to most forms of neuropathy. No matter what the cause of your nerve damage, you may be unfortunate enough to also need chemo treatment in the course of your life. It's important to realise that chemotherapy can both bring on and worsen neuropathy as a side effect. You may not have much choice and the chemotherapy will probably be more urgent than the possible consequences but knowing what to expect will help come to terms with it if it happens. Very often just knowing why something is happening to you is a help in itself.

Complementary Therapies For Chemo-Neuropathy: An Integrative Oncologist’s Bag Of Tricks
Published June 10, 2013 by Brian D. Lawenda, M.D.

“Chemotherapy-induced peripheral neuropathy” (CIPN) effects the lives of up to 40% of cancer patients who receive chemotherapy.

CIPN symptoms can be so bothersome that we have to lower our treatment doses or stop treatment all together.

Integrative oncology focuses on helping our patients get through their prescribed treatments with as minimal side effects as possible by using a combination of conventional and complementary approaches.

In this article you will briefly learn about CIPN and how it is treated with an integrative oncology approach.

COMMON CIPN SYMPTOMS:

Most commonly, these drugs cause symptoms (i.e. pain, burning, stabbing, numbness, tingling, temperature sensitivity) in the hands and feet. In more severe cases these symptoms move up the arms and legs. It can make it difficult to perform normal day-to-day tasks like buttoning a shirt, sorting coins in a purse, or walking.

In some instances patients can develop weakness of legs and leg cramps, numbness around your mouth area, constipation, pain during bowel movements, balance problems, hearing loss, jaw pain, trouble swallowing and trouble passing urine.

RISK FACTORS FOR CIPN:

The risk and severity of CIPN varies based on the individual drug(s), combinations of drugs, having received prior chemotherapy, your nutritional status, the duration and dose of your chemotherapy and genetic factors that predispose some individuals to more severe neuropathic symptoms.

CANCER-FIGHTING DRUGS THAT CAN CAUSE CIPN:

Platinum drugs, such as cisplatin (Platinol), oxaliplatin (Eloxatin), carboplatin (Paraplatin)
Taxanes, such as paclitaxel (Taxol, Abraxane), docetaxel (Taxotere)
Vinca alkaloids, such as vincristine (Oncovin, Vincasar), vinorelbine (Navelbine), and vinblastine (Velban)
Podophyllotoxins, such as etoposide (Etopophos, VePesid, Toposar, VP-16) and teniposide (Vumon)
Epothilones, such as ixabepilone (Ixempra)
Thalidomide (Thalomid) and lenalidomide (Revlimid)
Bortezomib (Velcade)
Interferon
Methotrexate (Rheumatrex, Trexall, Amethopterin, MTX)
Fluorouracil (5-FU, Adrucil)
Cytarabine (Cytosar-U)

HOW DOES CIPN DEVELOP?

We don’t know exactly, however the specific physiologic mechanisms likely vary depending on the drugs used.

One proposed theory:

Nerves have a covering (myelin) that protects them from damage and ensures that they work properly. One of the proposed theories is that CIPN can develop as a result of damage to the myelin covering through drug-induced free radical production in and around the nerves. Nerves with damaged myelin can’t send signals properly. It is believed that numbness occurs when nerves are no longer transmitting a signal, tingling happens if a false signal is sent and pain is felt when information overloads your unprotected nerves.





CIPN may develop as a result of nerve injury at various anatomic regions of the nerve depending on the specific drug.

CONVENTIONAL TREATMENTS; MANAGEMENT FOR CIPN:

Unfortunately, the pharmaceutical industry has not been able to develop a drug that has been proven to work all that well for CIPN. All the drugs we currently use to treat CIPN are actually commonly prescribed for use in other conditions (i.e. depression, pain, muscle spasms.) Although these drugs have some effect on reducing CIPN severity, they are not that effective in most patients and often have untoward side effects. For this reason, I believe in combining complementary therapy approaches along with these less than perfect drug therapies to hopefully get greater symptom relief.

Although this article focuses mainly on the use of non-pharmacologic complementary therapies for neuropathy, to be more complete I’ve added the list below of some of the more common CIPN drug therapies:

Antidepressant (i.e. duloxetine, venlafaxine, amitriptyline) for tingling and numbness
One study showed that 59% of those on duloxetine reported reduced pain, compared to 39% on placebo
Anticonvulsants (i.e. phenytoin, carbamazepine) for pain
Muscle-relaxant (i.e. baclofen)
Analgesic (i.e. ketamine)
Steroid for short-term use
Lidocaine patches
Opioids or narcotics for severe pain
Cannabinoids (i.e. marijuana, Marinol)

IV CALCIUM AND MAGNESIUM DOES NOT REDUCE THE SEVERITY OF RISK OF DEVELOPING OXALIPLATIN-INDUCED NEUROPATHY:

One of the ways that oncologists have tried to reduce the severity of oxaliplatin-induced neuropathy is by giving an IV infusion of calcium and magnesium during chemotherapy. This practice become widespread after a 2004 study reported an approximate 50% reduction in the rate of neuropathy when IV calcium and magnesium were given with oxaliplatin. Although this study was not a randomized study (no comparison against a placebo), many oncologists adopted this worldwide due to the large apparent improvement in neuropathy.

A lesson learned…

The reason why it’s important to remain a bit skeptical of studies that are not randomized trials was highlighted last week when a ‘practice changing’ placebo-randomized study (presented at the main international cancer conference, 2013 Annual ASCO meeting), found no benefit of giving calcium and magnesium infusions during oxaliplatin in reducing the risk or severity of neuropathy.

The bottom line: It is time to stop using calcium and magnesium infusions for the prevention of oxaliplatin-induced neuropathy.

MANY COMPLEMENTARY THERAPIES ARE USED IN THE MANAGEMENT OF CIPN:

The latest caclium-magnesium report (above) highlights a problem we see in many studies in which preliminary reports look very promising, but later randomized trials show no significant beneficial effects of the intervention. Complementary therapies are often not subjected to the same rigorous, high-quality trials that are used for drug or medical devices, so I remain cautiously optimistic on these therapies.

The integrative oncology approach to managing CIPN:

While I sit back and wait for more high-quality complementary therapy research in CIPN management, I inform patients on these therapies as long as the risk of harm (and cost) for the therapy is low and efficacy has been reported in (at a minimum) an academic, peer-reviewed publication or presentation.

As I mentioned above, I believe that combining pharmaceutical therapies for CIPN along with complementary therapies may be the most efficacious way to reduce these symptoms and get our patients through their cancer treatments more easily or improve their quality of life after treatment.

So, without further ado, here are some of the most commonly used complementary therapies for CIPN management:

DEVICES:
Transcutaneous Electrical Nerve Stimulation:

TENS works by causing muscle contractions that essentially causes blood to pump through the small blood vessels in the tissues, increasing the flow of oxygen and other nutrients into the tissues. It is believed that this influx of nutrients and oxygen aids in the healing process of the tissues and nerves. (Figure: TENS unit applied to affected areas on the feet)

Low Level Light Therapy (LLLT) or Cold Laser Therapy and Infrared Light Emitting Diode (LED) Therapy:
LLLT lasers and LEDs produce a low energy light that penetrates up to an inch below the skin surface. The energy is so low that for most LLLT lasers and LED devices the patient feels nothing when the light is shining on the skin. Studies have shown that the use of these devices causes analgesic (pain killing), anti-inflammatory and other metabolic and hormonal effects in the tissues that can speed up the body’s natural healing mechanisms (i.e. skin, mucous membranes, cartilage, tendons, nerves.) As with TENS therapy, LLLT also increases blood flow in the tissues, enabling higher levels of oxygen and other nutrients to reach the tissues.

Cryotherapy:

The use of cold cap therapy (frozen caps) has been very successful in helping patients keep their hair during chemotherapy. The same cryotherapy concept is available for your hands and feet with frozen gloves and slippers, however instead of sparing your hair you can reduce the toxicity of chemotherapy to your skin, nails and nerves. Wearing cold gloves and slippers decreases the blood flow to the tissues, thereby diminishing the amount of chemotherapy reaching your nerves in hands and feet during the infusion session. To be effective, the gloves and slippers need to be worn immediately before and during the entire chemotherapy infusion session. As with cold cap therapy, every 15-30 minutes you exchange the gloves and slippers with another pair from the freezer to keep your hands and feet cold. Northwestern University is currently enrolling breast cancer patients on Paclitaxel in a clinical trial to further assess the effectiveness of this therapy.

RELAXATION & PSYCHOLOGICAL THERAPIES:


Meditation:
Meditation is a practice (there are many forms of meditation) in which an individual focuses their awareness away from the distractions of the fleeting thoughts racing through our mind and onto an activity free of distraction (i.e. your breath, listening to relaxing music.) This leads to a state of consciousness where your mind becomes more free of scattered thoughts and towards a more calm and relaxed state. Meditation has been studiedand found to provide reduction in CIPN symptoms. 

Guided imagery (GI):
GI is a form of meditation or self hypnosis that focuses and directs your imagination through verbal suggestion and thoughts (using all of your senses: visual, sounds, touch, taste, smell) to improve physical and mental symptoms and conditions (i.e. pain, fatigue, nausea, immune support.) GI has been reported to be helpful for patients with pain syndromes (not specifically CIPN) during and after cancer treatment. Guided imagery often uses CD’s or DVD’s to guide you into your desired state

Biofeedback:
Biofeedback has been shown to be helpful in the management of pain syndromes (not specifically CIPN), and has been suggested to be a useful complementary therapy for CIPN. Biofeedback uses a device that measures your heart rate (or more specifically, the beat-to-beat variability in your heart rate) while you are performing a relaxation technique (i.e. concentrating on your breathing, visualizing a relaxing scene or imaging pain dissolving away.) As you are performing this relaxation technique or pain reduction imagery, you are able to watch or listen to your body’s response with a visual display or auditory tone (of your heart rate variability.) Read more about this on our blog.

Hypnosis and Self Hypnosis:

Hypnosis has been reported to be helpful for patients with pain syndromes (not specifically CIPN) during and after cancer treatment. Self-hypnosis has been shown to result in significant reduction in pain levels. You can teach yourself this technique with training from a medical hypnosis specialist (individually or in group sessions) or through books, CDs or DVDs. One of my favorites is called Hypnosis House Call. Hypnosis is basically a technique that combines guided imagery and meditation.

Cognitive Behavioral Therapy (CBT):

CBT is based on the fact that our thoughts are an important factor in how our mind and body processes our sensations (such as CIPN pain). CBT focuses on the fact that we can change the way our thoughts can alter our perception of these sensations. Therapists and psychologists who practice CBT teach their patients new ways to think about these sensations which help to relieve their discomfort. CBT has been reported to be helpful for patients with pain syndromes (not specifically CIPN) during and after cancer treatment.


CBT practitioners teach their patients that all components of this self-perpetuating cycle can be controlled by you using CBT techniques

PHYSICAL AND OCCUPATIONAL THERAPIES:

Physical Therapy:

Physical therapy (PT) focuses on helping patients improve their quality of life through increasing range of motion, strength, flexibility, balance and avoidance of activities or movements that make these factors worse. A Physical therapist with experience in treating patients with CIPN will be able to formulate a personalized treatment plan so the CIPN will not be exacerbated. Depending on the specific circumstances, a physical therapist may use a variety of techniques: soft tissue techniques, padding over painful skin areas, heat therapies, electrical stimulation (i.e. TENS), ultrasound, vibrational platforms, LED or LLLT therapies, balance systems, therapeutic exercise, functional activities.

Occupational Therapy

Occupational therapy (OT) is used to help you cope with the impact CIPN can have on various aspects of your life. OT improves sensory and motor skills, teaches you self-care activities and safety awareness, and provides you with techniques for maintaining mobility, stability and range of motion with your hands and fingers. OT teaches you alternative ways to accomplish everyday tasks that may otherwise be difficult (i.e. if you have trouble buttoning shirts, OT may be useful in providing you with a new technique, or a special tool that can aid in grabbing buttons and passing them through loops.) OT also emphasizes protecting yourself while performing everyday tasks. Because many patients with CIPN lose feeling in their hands and feet, it may be necessary to take several steps to ensure that everyday tasks are safe (i.e. before bathing or showering, use a thermometer to test the temperature of the water, use pot holders when cooking or handling items on a stove or in an oven, use thick gloves when washing dishes or working with sharp utensils, inspect hands, feet and the skin of other neuropathy-affected areas daily for any abrasions, blisters, burns or wounds, and treat any injuries promptly.)

MASSAGE, YOGA AND ENERGY THERAPIES:

Energy therapies are based on the belief that a “vital energy” flows through our body, and by balance this energy flow we can promote health, healing and symptom relief.

Massage:

Massage has been reported in studies to be helpful for relieving pain (not specifically CIPN pain.) It is believed that massage may facilitate the healing of nerves by improving blood circulation to the affected tissues (increasing oxygen and nutrient flow.) Massage also increases the production of natural pain-killing proteins (called, endorphins) in the tissues being massaged. Choose a massage therapist with experience in working with those with cancer or a cancer history.

Acupuncture:

Acupuncture has been reported to help restore nerve function in patients with CIPN. Studies have shown that acupuncture increases blood flow in the limbs (aiding in oxygenation and nutrient delivery to the affected tissues and nerves.) Choose an acupuncturist with experience in working with those with cancer or a cancer history.

Reiki:

Reiki is a Japanese technique for stress reduction and relaxation that also promotes healing. It is administered by “laying on hands” and is based on the idea that an unseen “life force energy” flows through us and keeps us healthy (mind and body.) The treatment involves the practitioner placing their hands on the patient in various positions (alternatively, practitioners may use a non-touching technique where the hands are held a few centimetres away from the patient’s body for some or all of the positions.) The hands are usually kept in a position for three to five minutes before moving to the next position. Some studies have found that reiki provides reduction in CIPN symptoms, although it is an area of controversy.

Yoga:

There are over 100 different types of yoga practiced in the United States today. Most of them are based on hatha yoga, which uses movement and postures (asanas), breathing exercises (pranayama), and meditation to achieve a connection between mind, body, and spirit. Yoga has been studied and found to provide reduction in CIPN symptoms. It is important to practice yoga with an instructor who is experienced in working with cancer patients, as they will need to guide you in making sure you do not injury yourself. Also, before taking a hot yoga (i.e. bikram yoga) class, ask your cancer doctor if this is safe for you. These are practiced in a very warm, humid room (usually between 95° and 105° F) and can be particularly hard on your body during active cancer treatments.

TOPICAL THERAPIES:

Capsaicin patch (made from chili pepper extract):

High concentration (8%) capsaicin patches have been reported to be beneficial in the management of neuropathic symptoms (not specifically CIPN.) This high concentration is about 100 times greater than conventional capsaicin creams that you can buy over the counter. High-concentration topical capsaicin is given as a single patch application to the affected part. It is normally applied with local anesthetic, due to the initial intense burning sensation it causes. The patch is left in place for 60 minutes and is then removed. The benefits last for about 12 weeks, when another application might be made.

SUPPLEMENTS:

You may be able to help your body repair CIPN nerve injury and reduce CIPN side effects by consuming certain foods, supplements and botanical compounds that are loaded with antioxidants and amino acids.
**IMPORTANT: Before starting any supplement, first discuss this with your doctors**

N-acetylcysteine (NAC):

N-acetylcysteine (NAC) is a powerful antioxidant and a precursor to glutathione, an antioxidant made by our body. By supplying our body with the building blocks for glutathione, studies report that NAC may be able to protect our nerves from CIPN. To date, definitive evidence on the effectiveness of NAC in CIPN management is still not known.
Doses: 1000-2000 mg per day

Lipoic Acid (LA), Alpha-Lipoic Acid or R-Lipoic Acid:

Lipoic acid (LA) is a potent antioxidant. Some data suggest that LA may be beneficial in reducing diabetic neuropathy, however it is less clear if LA is helpful in patients with CIPN. To date, definitive evidence on the effectiveness of LA in CIPN management is still not known. The most biologically active form of LA for nerves is called R-Lipoic Acid (R-LA.) CIPN symptoms should start to improve within 4-6 weeks (per Harvard/Dana Farber Cancer Institute). If you don’t notice any improvement after that time, it probably won’t be helpful for you by continuing it any longer.
Doses: R-Lipoic Acid (240 – 480 mg daily) or Alpha-Lipoic Acid (500 – 1000 mg daily)

Acetyl-L-Carnitine (ALC) or L-Carnitine:

Carnitine is an amino acid predominately found in red meat. But it can be consumed in supplement form as acetyl-L-carnitine (ALC). Acetyl-L-carnitine has been reported to reduce the severity of CIPN, although the mechanisms of action of ALC are not clear and are likely to be multifactorial, with effects on circulating neurotrophins, mitochondrial function (including anti-apoptotic effects), and synaptic transmission influencing both nerve structure/ function and patient perception of neuropathic symptoms. To date, definitive evidence on the effectiveness of ALC in CIPN management is still not known.
Doses: Oral doses from 1,000 mg once-per-day to 1,000 mg three-times-per-day

Curcumin:

Curcumin is the main active phytonutrient extract from turmeric (the yellow-orange root that gives curry powder its distinctive color.) Curcumin is a powerful antioxidant and anti-inflammatory compound (read more about the amazing anti-cancer properties of curcumin in our post.) Studies have shown that curcumin has efficacy in the treatment of diabetic neuropathy and possibly in CIPN. It is important to buy a curcumin formulation that is designed to have a greater bioavailability than standard curcumin formulations, as curcumin is not absorbed well across the bowel wall.
Doses: 400-800 mg per day

Vitamin B6 (pyridoxine):

Studies suggest that vitamin B6 may alleviate neuropathy (not specifically CIPN). Clinical trials are underway to determine if vitamin B6 (50 mg, 3-times per day) is effective in preventing CIPN. To date, definitive evidence on the effectiveness of vitamin B6 in CIPN management is still not known.
Dose: 50 to 100 mg per day. If you are taking a multivitamin and/or B Complex, check the amount of B6 so that you do not go above 100 mg total per day (as higher levels of B6 can actually cause neuropathy symptoms.)

Vitamin B12:
Studies suggest that vitamin B12 may alleviate neuropathy (not specifically CIPN). Clinical trials are underway to determine if vitamin B12 is effective in preventing CIPN. The natural form of B12 found in food is methylcobalamin, which appears to be the most effective form to protect our nerves.
Dose: (methylcobalamin) 1-2 mg per day

Omega-3 Fatty Acids (EPA, DHA):
Omega-3 fatty acids (eicosapentaenoic acid or EPA and docosahexaenoic acid or DHA) are found in high quantities in cold water fish (i.e. salmon, mackerel, sardines, cod) and krill (a tiny shrimp). EPA and DHA are called “essential fatty acids.” Essential fatty acids are not able to be made by our body (they have to come from our diet) and are important components of our cell membranes, including the protective nerve sheath covering (myelin). It is almost impossible in our Western diet (which is typically very low in EPA and DHA) to consume a high enough amount of these fatty acids to repair and protect our nerves from CIPN. Taking a high-quality (low-toxin content) omega-3 fatty acid supplement is therefore recommended (check out the Environmental Defense Fund’s list of safe fish oil supplements.) Certain vegetables, nuts and seeds also have an omega-3 fatty acid called alpha-linolenic acid (ALA), but this fatty acid is not in the 2 forms (EPA and DHA) that our body uses. ALA can be converted in our body to EPA and DHA, but this conversion is not very efficient. Most experts agree that consuming foods or taking a supplement in the EPA and DHA form is far superior to those in the ALA form that requires an inefficient conversion to be useful. Studies show that EPA and DHA are able to protect against CIPN when taken during chemotherapy.
Doses: 4000 mg daily, providing at least 1400 mg EPA and 1000 mg DHA

Vitamin E (Tocopherols and Tocotrienols):

Vitamin E is a potent antioxidant that has been reported to be effective in the prevention of CIPN. The term “vitamin E” refers to a family of eight related, lipid-soluble, antioxidant compounds widely present in plants. The tocopherol and tocotrienol subfamilies are each composed of alpha, beta, gamma, and delta fractions having unique biological effects.
Doses: 400 IU per day (with around 200 mg gamma tocopherol). One of my favorite products is: Gamma E Tocopherol/Tocotrienols

Glutamine (L-Glutamine):

Glutamine is an amino acid that has been reported to be effective in the prevention of CIPN. Although glutamine is the most abundant amino acid in the body, it has been found that many people with cancer have low levels of glutamine. Glutamine, usually in the form of L-glutamine, is available by itself or as part of a protein supplement. These come in powder, capsule, tablet, or liquid form.
Doses: (L-Glutamine) 10 grams, three-times-per-day or 15 grams, twice-per-day

Summary and Additional Resources:

There are many treatment and prevention options available to you for CIPN management. I recommend that you start with one or two option(s) at a time and give it a few weeks to see if it works for you. Start with therapies that are the most convenient, least expensive and available in your area. Work with your cancer care team in selecting the therapy and practitioner so that everyone is on the same page and knows what you are doing and with whom. Consulting with an integrative oncologist is always helpful when formulating your care plan.

Additional Resources:

Neuropathy Care For Cancer Survivors (Memorial Sloan-Kettering Cancer Center): Great 4-part video on helping survivors better understand the treatment and management of neuropathy
Chemotherapy Neuropathy Treatment (Beating Neuropathy Radio)
Neuropathy (Livestrong)
Managing Peripheral Neuropathy (Cancer.Net)
Chemotherapy-Induced Neuropathy (NCI Cancer Bulletin)
Peripheral Neuropathy Caused By Chemotherapy (American Cancer Society)
Categories: Side Effects

About Brian D. Lawenda, M.D.
I am an integrative oncologist. I trained at Massachusetts General Hospital (Harvard Medical School) in radiation oncology and through Stanford-UCLA (Helms Medical Institute) in medical acupuncture. I am the founder of IntegrativeOncology-Essentials.

http://www.integrativeoncology-essentials.com/2013/06/complementary-therapies-for-chemo-neuropathy/