Neuropathy in cancer patients: how nerve damage develops

Mechanisms, risk factors, prevention of neurotoxic consequences of cancer therapy

Information from the internet can give you an overview. They are not intended to replace the advice of a doctor.

In some tumor patients, damaged nerves occur as a result of treatment with cancer drugs. Radiation therapy or the tumor itself can also damage nerves. The disorder may be temporary, but in some sufferers it may persist. From the "neurotoxic In most patients, the nerves that are responsible for tactile sensation, temperature perception and the transmission of stimuli and pain are affected. Experts refer to this damage as "neuropathy". Preventing neuropathy is only possible to a limited extent so far.

This text is intended for patients, their relatives and interested parties. It offers answers to the following questions: what are the possible causes of nerve damage in cancer patients?? Which nerves are often affected? Can nerve damage be prevented or detected early?? Important to know: when it comes to diagnosis or treatment, information from the Internet is no substitute for a discussion with the treating physician.

Causes: when does nerve damage occur in cancer patients??

Cancer drugs can damage nerves. Image: tobias schwerdt © cancer information service, german cancer research center

Cancer treatment is a frequent cause of nerve damage in cancer patients: some chemotherapy drugs in particular damage the nerves.

Even during surgery and some radiation therapies, it is not always possible to avoid damaging small nerves. After surgery, for example, there is numbness or sensitivity to touch of the skin around the scar. Finally, the tumor itself can destroy nerves by growing around them or pressing on them.

Especially in cancer patients with advanced tumor disease, it can often be difficult for physicians to determine the true cause of neuropathic symptoms right away. For many tumor patients, several factors play a role.

Important questions for the diagnosis are therefore: Are there other risk factors, such as pre-existing conditions??

Cancer patients bear a higher risk of nerve damage as a result of cancer treatment

  • With other diseases such as diabetes, kidney weakness, hypothyroidism, connective tissue diseases and inflammatory rheumatic diseases,
  • With frequent alcohol consumption,
  • With vitamin deficiency (especially B1, B6, B12),
  • With an infection caused by HIV and
  • With congenital risk-increasing changes in the genetic makeup.

Are older cancer patients more at risk? The extent to which an older age favors the occurrence of nerve damage during cancer treatment has not yet been conclusively clarified.

How neuropathy becomes noticeable

Talk to your doctor to find out if you are at risk for nerve damage.

What was previously perceived as normal touch can suddenly become unpleasant or painful with the onset of nerve damage. Some patients perceive pressure, touch, pain or vibration and temperature only weakly or not at all anymore. In others, feet and hands become numb and it is difficult for them to grip, write or walk safely. Still other patients feel a tingling sensation or "ants’ feet" in the soles of the feet or fingertips.

If it is not the nerves in the arms or legs that are affected, but rather the cranial nerves? Patients may then have poorer hearing or vision.

All in all, these stressful symptoms of nerve damage often severely restrict patients in their daily lives and quality of life.

Cancer drugs: which drugs damage nerves??

What most often causes neuropathic problems? The statistics show: chemotherapy drugs belonging to the group of platinum compounds, taxanes, vinca alkaloids, and the substance eribulin. These substances frequently to very frequently damage peripheral nerve tracts of cancer patients.

How many people are affected?

Some cancer drugs damage the nerves. Image: tobias schwerdt © cancer information service, german cancer research center

It is difficult to give concrete probabilities: the figures in the literature are often inconsistent and not always comparable.

Whether or not neuropathic symptoms occur in an individual cancer patient depends on various factors: the drug itself, but also the respective single dose, the total dose during the entire treatment, as well as the infusion time and the treatment duration.
It is also relevant whether different nerve-damaging cancer drugs are given in combination, such as taxane plus carboplatin. In addition, there are individual risk factors that have nothing to do with the cancer treatment or the cancer disease.

This means that anyone who wants to find out about their individual risk should talk to the doctors treating them – they are best placed to give an assessment because they know the personal situation and the specific treatment plan.

What medications are involved?

Many chemos and other cancer therapies are given directly to the patient in the clinic or practice, for example as a mixture in an infusion. If you therefore do not know exactly what you are being treated with – ask your doctors!

Platinum-containing chemotherapy drugs
These include, for example, oxaliplatin, cisplatin and carboplatin. oxaliplatin statistically causes acute insensitivity, especially to cold, in a very large number of patients immediately after drug administration. These usually disappear on their own after a few days.
Longer-lasting peripheral neuropathies after oxaliplatin administration affect fewer patients.

If patients receive cisplatin, the likelihood of inner ear damage is high. Patients may experience hearing problems, especially with high-pitched sounds, but also ear noise or balance problems because the sense of balance in the inner ear is also affected. Tingling in the hands and feet, coordination problems or gait unsteadiness are also common. Rarely, temporary visual disturbances occur. Persistent eye damage is very rare. Whether hearing disorders can be prevented by administering sodium thiosulfate is the subject of current research. In a study with children suffering from cancer, the risk was significantly reduced in this way.

The likelihood of being impaired in the long term depends on the dosage of cisplatin. Measurable, persistent symptoms can occur in almost one-third of all patients after a single dose.

carboplatin can also cause symptoms similar to those seen with cisplatin. After platinum-based chemotherapy is completed, neuropathy may worsen in some affected patients. Experts speak of the so-called coasting phenomenon.

an example of a neurotoxic agent from this group is the active ingredient paclitaxel. All degrees of sensory disturbances are observed very frequently.

Vinca alkaloids
these include, for example, vincristine, vinblastine and vinorelbine. Neuropathies of all degrees of severity are very likely to occur with these drugs.

Other chemotherapy drugs
there is still a certain risk of such impairments with other chemotherapy drugs. However, it is significantly lower and the neuropathies are less pronounced.

Targeted drugs: However, chemotherapeutic agents are not the only triggers of neuropathies.
Some targeted cancer drugs can also impair the function of nerve fibers. These include, for example, bortezomib and thalidomide.

Radiation, surgery, tumor: when do they trigger a neuropathy??

Radiation as a trigger

Radiation can damage nerve pathways that lie in the radiation field. This happens comparatively often when larger nerve plexuses have to be irradiated as well. The nerves themselves are either directly damaged, or the irradiated tissue hardens over time and presses on the nerves.

Whether nerve damage occurs and how severe it is after radiation therapy depends on the following factors:

  • How high is the daily dose of radiation therapy received??
  • What is the total radiation dose??
  • If nerve-damaging drugs are given at the same time or have been given in the past?
  • Are there pre-existing and concomitant diseases that favor nerve damage??

Surgery as a trigger

Nerve damage cannot always be avoided during surgery. These can also lead to numbness or discomfort in the areas of the body supplied by the affected nerves. Typical examples are sensory disturbances, especially in the skin around the wound.
Regeneration of the injured nerves is possible, and many patients experience improvement after some time.

Tumor as a trigger of neuropathy

They often burn or sting. This distinguishes it from most pains with other causes.

If a tumor presses on or grows into nerve pathways, their function is impaired or, in the worst case, even destroyed. Affected persons then often experience burning and stabbing pains. They are considered to be particularly typical neuropathic pains.
How this differs from other types of pain and what can be done about it is explained in more detail in the texts under the heading pain therapy in cancer patients.

Localization: which nerves are predominantly affected?

Peripheral nerves: nerve pathways outside the brain and spinal cord
autonomic nervous system: nerves that cannot be influenced voluntarily and control the internal organs
central nervous system: brain and spinal cord

Peripheral nervous system
the nerve-damaging effects of most neurotoxic therapies predominantly affect longer peripheral nerve tracts. They are responsible for tactile sensation, temperature perception and pain transmission, so the signs of damage look the same.
Depending on the situation, nerves that stimulate muscles may also be damaged. This can lead to hypersensitivity to touch, lack of temperature sensation, burning pain, muscle weakness or numbness.

Vegetative nervous system
side effects on so-called autonomic nerves occur less frequently after the administration of cancer drugs. These are nerves that cannot be influenced by the human will: they control, for example, internal organs such as the intestine, bladder and cardiovascular system.
The consequences of damage can include persistent constipation or blood pressure problems.

Central nervous system
only a comparatively small number of cancer drugs can affect the brain or spinal cord, the so-called central nervous system. Examples include the chemotherapy drugs cytarabine, ifosfamide or methotrexate, and platinum compounds.
How does this become noticeable? Those affected may then suffer from headaches, feel listless and tired.
In most patients, these symptoms subside quickly. Whether patients experience long-term limitations after chemotherapy, for example in their ability to remember things, is still unclear and is being investigated in studies.

Biology: how does damage to peripheral nerves occur??

What is it exactly that makes the individual cytostatic drugs in particular so damaging to the nerves??
Knowledge about the damage mechanisms of individual chemotherapy agents is still insufficient. But in recent years, scientists have been conducting more and more targeted research into these causes.

Nerve damage caused by cancer drugs

nerve cell in action © psdesign1 – stock.Adobe.Com

Experts suspect different mechanisms, depending on the anticancer drug used: some drugs destroy the nerve endings or the insulating sheath around the nerve cell processes. Or they alter the channels through which the exchange of substances between nerve cells and tissue takes place, and which are important for the transmission of stimuli.

Other drugs affect the function of structures inside a nerve cell. These include, for example, microtubules, which are part of the "cytoskeleton", or mitochondria, the "power plants" the cell.
Still others destroy small blood vessels around the nerve cells so that they are not supplied with sufficient nutrients.

Nerve damage from other causes

Damage to peripheral nerves can also occur indirectly, not only through the influence of cancer drugs. The cause is then usually an impairment of the entire surrounding tissue. This is the case, for example, with radiation-induced hardening of the skin and tissue, a "sclerotherapy".
chemotherapy can affect not only the nerves directly, but also the blood supply: if it is reduced, all the affected tissue suffers along with the nerves.
But even if the tumor grows and presses on nerve tissue from the outside, nerve tissue can be destroyed or damaged.

Risk factors: what influences the extent of neuropathy??

Whether nerves will be damaged, and if so, how severely, is not always something doctors can assess in advance of cancer treatment. As a patient, you can use the following questions to prepare for a consultation. They help to get more clarity about one’s own risk:

  • Are the cancer drugs that are being considered for my treatment damaging to my nerves??
  • Can the risk of neuropathy be reduced, for example by lowering the drug dose or choosing a different drug?? What consequences would this have for the success of my treatment??
  • Will I also receive radiation treatment? This increases the risk of neuropathy? Are other nerve-damaging treatments being used at the same time?
  • Do I have concomitant diseases that can cause damage to nerve tracts?? Do you see any signs of neuropathy in me already?? How do these affect my risk of further nerve damage from cancer treatment??

Prevention: can something be done to prevent damage to peripheral nerves??

Benefits and risks of a change in therapy for nerve damage should be discussed with a doctor. Image: tobias schwerdt © cancer information service, german cancer research center

Do not use drugs that damage nerves
for most anticancer drugs with neurotoxic effects, the safest way to prevent symptoms is still to switch to a less or non-neurotoxic drug. However, this is not possible for all cancer patients without drastically reducing the chances of cure.

Low dosage
at the first signs of neuropathic symptoms, physicians reduce the chemotherapy dose if possible. If the distressing neurological symptoms nevertheless worsen, it may be necessary to discontinue treatment in some patients. In some circumstances, a longer break from therapy can also help.

Weighing the benefits against the risks
especially in the case of cancer therapy with the prospect of a cure, patients and physicians should discuss the benefits and risks of these measures together.
The following questions can only be answered individually:

  • How much would the nerve damage burden me in the long term and limit me in my everyday life?
  • What influence do the symptoms have on my quality of life??
  • Which risk is more serious for me: the possibility of neuropathy due to cancer therapy?? Or the risk that my chances of recovery will decrease if the dose is reduced, a break in therapy is taken, or I have to switch to another, less effective drug?

Nerve-protective drugs for prevention?

So far, it is not possible to prevent nerve-damaging side effects of chemotherapy with drugs.

Scientists have been searching for years for drugs that prevent or at least alleviate nerve damage. Optimal would be nerve-protecting substances that affected patients could receive before chemotherapy. So far, however, no such drug exists.

What is being researched?
Agents such as acetylcysteine, alpha-lipoic acid, glutathione, amifostine, calcium, magnesium, carbamazepine, vitamin E and other substances have been and are being investigated in studies. However, there is still no convincing proof of their efficacy and safety.
A current guideline therefore advises: acetylcysteine, alpha-lipoic acid, glutathione should not be used to prevent chemotherapy-induced nerve damage. Also amifostine, calcium, magnesium, carbamazepine, vitamin E should not be used.

The situation is similar with protection against hearing problems: drugs that protect patients against chemotherapy-induced hearing disorders are also the subject of current research.

occupational therapy, electrotherapy, sensorimotor training, vibration training for prevention?
Medicine knows a number of ways to stimulate the sense of touch or, more generally, the transmission of stimuli via the skin. A current guideline lists some examples:
This includes occupational therapy exercises in the so-called "bean bath", a tub filled with beans, other grains or small balls; or even electrotherapy to stimulate the nerves specifically. But whether these applications are of any use in preventing nerve damage is currently unclear. According to the guideline, they can be used if they do not cause skin damage or aggravate existing skin problems.
Also not yet proven as a preventive measure: targeted sensorimotor training by physiotherapists or occupational therapists or vibration training with suitable equipment.
In order to prove the effectiveness or ineffectiveness of such procedures, meaningful studies on the subject have yet to be carried out.

Cold gloves and socks for prevention?
Studies are also being conducted to determine whether peripheral nerve damage can be avoided by restricting the blood supply to the particularly sensitive hands during the infusion of cytostatic drugs. The idea behind this is to prevent the drugs from getting to the nerves in the first place. This can be done, for example, by supercooling with special "ice"- or reach cool gloves and socks.
Questions about the benefits and possible risks are still unanswered.

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