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Institute for Preventive Foot Health (IPFH): How Chemotherapy Can Affect the Feet

If chemotherapy is part of your cancer treatment, be aware that side effects may include conditions that affect the feet. The two most frequent are hand-foot syndrome (also called palmar-plantar erythrodyesthesia or PPE) and chemotherapy-induced peripheral neuropathy (CIPN).


Hand-foot syndrome

Hand-foot syndrome usually manifests as redness, swelling, and pain on the palms of the hands and/or the soles of the feet. Sometimes it is accompanied by blisters, peeling of the skin, and rashes. Less frequently, it may occur in other areas, including knees and elbows.

The National Cancer Institute (NCI) has a simple grading system for different levels of severity of hand-foot syndrome. Grade 1 describes skin changes or dermatitis without pain. Grade 2 describes skin changes with pain that do not interfere with the functioning of the hands or feet. Grade 3 describes skin changes with pain that do interfere with the functioning of the hands or feet.


  • Redness, often accompanied by swelling;
  • Rash;
  • Blisters or calluses on the soles of the feet and/or on the palms of the hands;
  • Difficulty walking due to foot pain, and/or difficulty in manual tasks due to pain in the hands;
  • Burning or tingling sensation (which can also be a symptom of neuropathy, or nerve damage);
  • Soreness or tenderness.

In severe cases, significant pain (9 or 10 on a scale of 10) may be present. The skin of the feet may dry and crack, and ulcers or open sores may develop, making it very difficult to walk.

NOTE: If you are undergoing chemotherapy and have these symptoms, it does not always mean that you are experiencing hand-foot syndrome. If you exercise regularly (or even if you don’t), you might experience other foot conditions that produce similar symptoms. Consult your physician, a podiatrist or other foot health professional to determine the origin of the pain or discomfort and to receive appropriate treatment. You may also use the IPFH foot pain self-assessment tool to see other possible causes of foot pain.


Various classes of drugs used in chemotherapy for breast cancer and other types of cancer can cause hand-foot syndrome. The syndrome is most commonly associated with 5 fluorouracil (5FU), liposomal doxorubicin, and cytarabine. 1

When chemotherapy drugs “leak” into healthy cells in the soles of your feet and the palms of your hands through the small vessels (capillaries) in the circulatory system, they cause damage. At that point, symptoms may be triggered even by pressure and friction from normal walking and standing, as well as normal use of the hands.

Prevention and Treatment

Hand-foot syndrome is difficult to prevent because it is caused by potentially life-saving cancer therapy. No effective treatments have been confirmed via clinical trials, although a recent small study showed that using topical aluminum chlorohydrate as an antiperspirant seems to reduce the severity of the condition. Some promising outcomes also have been achieved with oral doses of vitamin E, and topical and systemic treatments with steroids, but these were in small case studies and the results cannot be generalized to the larger patient population.

Generally, physicians try to treat the symptoms:

  • In severe cases, chemotherapy treatments may be suspended or dosages lowered until symptoms become less painful;
  • Medications such as ibuprofen, naproxen and other over-the-counter remedies may be prescribed to help relieve pain;
  • Topical creams that contain anesthetic ingredients (lidocaine, xylocaine and others) may be used to reduce pain in palms and on the soles of the feet;
  • Ice packs applied to areas of the hands and feet where swelling and pain occur can help reduce symptoms;
  • Moisturizing creams and topical treatments that contain urea or other commonly used moisturizers can help with dry skin and peeling, but do not use urea-based moisturizers on open wounds.  
  • Padded socks and cushioned or accommodative footwear can help reduce painful pressure on the feet. IPFH recommends using the integrated approach to get properly sized and fitted for padded socks and footwear.

Additional strategies may include:

  • Using hand tools as little as possible to avoid further inflammation of already affected areas on the hands;
  • Avoiding extended exposure to heat or hot water on your hands and feet;
  • Taking frequent breaks during exercise to take pressure off the feet.

Medical Considerations

One of the primary concerns with hand-foot syndrome is the potential infection of peeling or cracking skin and open sores. Use antibiotic creams and cover any open wounds or exposed areas with bandages. Over-the-counter burn pads and bandages may also be helpful. If any indication of infection occurs, consult a physician immediately. Common signs of infection are redness and swelling around a sore, a warm feeling when touched, the presence of pus, and sometimes red streaks in the area near the sore.

If you suspect that you have hand-foot syndrome as a result of chemotherapy, and especially if the discomfort and pain interfere with your ability to walk and/or use your hands normally, consult your oncologist, your primary care physician, or a podiatrist or other foot health professional.


Chemotherapy-induced Peripheral Neuropathy (CIPN)

Peripheral neuropathy is damage to nerves in areas of the body outside of the central nervous system (the brain and spinal cord). It mainly affects the feet and the hands, often producing numbness or burning pain and weakness in the muscles that interfere with your ability to function normally and comfortably. The greatest danger of extended numbness and lack of sensation in the feet is unrecognized trauma.

Chemotherapy-induced peripheral neuropathy typically occurs when chemotherapy drugs circulating in the body damage the nerves.  A number of approaches have been tried to help prevent this nerve damage, but with only minimal evidence of success in clinical trials. 2


Symptoms associated with neuropathy of the feet include:

  • Lack of sensation;
  • Tingling or burning pain radiating through the feet and toes;
  • Difficulty keeping balance or walking.

According to the American Cancer Society, in most cases, symptoms start in the feet, and over time may occur in other parts of the body:
“Symptoms tend to start farthest away from the head, but move closer over time. In most cases, people will notice chemo-induced peripheral neuropathy symptoms in the feet, then later on in the hands. Symptoms may start in the toes, but move on to the ankles and legs. Likewise, symptoms can move up from the fingers to the hands and arms.”  

There also may be sensitivity to cold or heat, muscle weakness, difficulty swallowing, changes in blood pressure, constipation and difficulty passing urine.

NOTE: If you experience symptoms of peripheral neuropathy and are taking chemotherapy treatments, do not assume that they are the result of the chemotherapy. There are other causes of neuropathy, so consult your oncologist or primary care physician to get a proper diagnosis.


According to the American Cancer Society, chemotherapy-induced peripheral neuropathy is associated most often with these drugs:

  • Bortezomib (Velcade®) and carfilzomib (Kyprolis®)
  • Epothilone (such as ixabepilone [Ixempra®])
  • Eribulin (Halaven®)
  • Plant alkaloids (such as vinblastine, vincristine, vinorelbine, and etoposide [VP-16])
  • Platinum drugs (such cisplatin, carboplatin, and oxaliplatin)
  • Taxanes including paclitaxel (Taxol®), docetaxel (Taxotere®), and cabazitaxel (Jevtana®)
  • Thalidomide (Thalomid®), lenalidomide (Revlimid®), and pomalidomide (Pomalyst®)

Prevention and Treatment

Little success has been demonstrated in preventing CIPN, and to date none of the approaches tested are recommended by the National Comprehensive Cancer Network task force due to the small studies with variable results, and concerns that the effectiveness of chemotherapy can be compromised by the medications. 2

Treatment options typically include:

  • Reducing the dosage of the chemotherapy drug;
  • Changing the treatment regimen completely;
  • Using adjunct medications such as topical analgesics, tricyclic antidepressants, anticonvulsants, and serotonin–norepinephrine reuptake inhibitors.

Other options include:

  • Prescription drugs (steroids, antidepressants, anti-seizure medications, opioids, topical analgesics) to treat symptoms of pain and discomfort;
  • Non-drug pain management approaches, such as physical / occupational therapy, relaxation therapy, meditation, and electrical nerve stimulation;
  • Proper footwear to help prevent pain from pressure and unrecognized trauma when sensation is lost. This may include padded socks and footwear fitted using IPFH’s integrated approach to selection and fitting.

Medical Considerations

CIPN may last for a limited amount of time, or it may be a long-term issue, depending on age, other medical conditions (such as diabetes), whether or not you are taking other medications, and the type, dosage and frequency of chemotherapy treatment. Exercise may be beneficial in managing symptoms of CIPN: In a recent study, investigators directly compared neuropathic symptoms in non-exercisers to those among patients who took part in a specialized six-week walking routine with gentle, resistance-band training at home. The exercisers reported significantly fewer symptoms of neuropathy, and the effects of exercise seemed to be most beneficial for older patients. 3   Always consult your oncologist or primary care physician without delay if you experience any symptoms of neuropathy, and ask about exercise programs that might be able to help.


Chemotherapy drugs are effective because they kill fast-growing cancer cells; however, because they circulate throughout the body, they may affect normally functioning, healthy cells as well. Not everyone experiences side effects, and side effects can vary in severity.  The most effective way of dealing with side effects like hand-foot syndrome and chemotherapy-induced peripheral neuropathy is to work with your medical team, and take steps to address any symptoms as soon as they arise.



1. Webster-Gandy JD, How C, Harrold K, “Palmar-plantar erythrodysesthesia (PPE): a literature review with commentary on experience in a cancer centre,” European Journal of Oncology Nursing, 11(3):238-246; 2007.

2. Piccolo J and Kolesar JM, “Prevention and treatment of chemotherapy-induced peripheral neuropathy,” American Journal of Health-System Pharmacy, January 1, 2014 71 (1), 19-25.

3. Kleckner,, A URCC NCORP nationwide randomized controlled trial investigating the effect of exercise on chemotherapy-induced peripheral neuropathy in 314 cancer patients, Journal of Clinical Oncology 34, 2016 (suppl; abstr 10000), presented at American Society of Clinical Oncology 2016 Annual Meeting.



Reviewed by: Lori S. Weisenfeld, DPM, IPFH Scientific Advisory Board
September 21, 2015 


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