What is Taxane Toxicity?
Taxanes are a type of chemotherapy drug that includes paclitaxel, docetaxel, cabazitaxel, and albumin-bound paclitaxel. They work by strengthening the tiny tubes (microtubules) in the body’s cells, causing those cells to stop dividing and eventually die off. This treatment method is commonly used to battle different forms of cancer.
Paclitaxel was the first drug in this group to be approved by the Food and Drug Administration (FDA) in 1992. It was originally used for the treatment of ovarian cancer when other treatments didn’t work. It’s now also used for a range of other cancers including breast, lung, bladder and AIDS-related Kaposi sarcoma. Docetaxel was approved by the FDA in 1996, initially for breast cancer treatment and now also for lung, head and neck, stomach, and ovarian cancers. Cabazitaxel is commonly used for prostate cancer that has resisted other treatment, while nab-paclitaxel is used for advanced pancreatic cancer, breast cancer, and non-small cell lung cancer.
Despite their effectiveness in treating different types of cancer, the use of Taxanes comes with some side effects. These effects could worsen when combined with other cancer drugs. Common side effects for all Taxanes include low blood cell count (myelosuppression), nerve damage (neuropathy), and allergic reactions. These drugs have also been known to cause stomach and intestinal bleeding.
Each Taxane comes with its unique set of side effects. Paclitaxel can cause slow heartbeat (bradycardia), hair loss, nail discoloration, and, less commonly, liver inflammation (hepatitis) and lung inflammation (pneumonitis). Docetaxel can lead to fluid retention, skin problems and mouth sores (stomatitis). Cabazitaxel can cause infections, nausea, vomiting, diarrhea, and constipation. Nab-paclitaxel tends to cause fewer allergic reactions, but it can also cause nausea, vomiting, hair loss, joint pain, muscle pain, and higher liver enzyme levels.
What Causes Taxane Toxicity?
Taxane toxicity is a common issue because these cancer-fighting drugs have unique molecular structures and are often used in cancer treatments. The first drug of this kind, Paclitaxel, was initially extracted from the bark of a tree called Taxus brevifolia, but today we mostly use artificially made versions of this drug. Another similar drug, docetaxel, was discovered in the needles of a different tree, Taxus baccata.
To properly disperse in the body and fight cancer, both paclitaxel and docetaxel need to be combined with certain solvents. The solvents used can sometimes cause allergic reactions during the infusion of the drugs. Some research suggests these reactions might be the body’s response to a specific kind of antibody called IgE.
Nab-paclitaxel is a specially designed version of paclitaxel formed into tiny particles and combined with albumin, a protein in our blood. Unlike its traditional counterpart, it doesn’t cause allergic reactions during the infusion. Cabazitaxel is another taxane designed to overcome the resistance some cancers build up to paclitaxel and docetaxel. However, because its structure is similar to docetaxel, it carries the same risk of any potential allergic reactions.
It’s important to be aware that paclitaxel can cause nerve damage. This usually affects the hands and feet and can become permanent if not treated. Other side effects include lowered white blood cell count (which can make you more susceptible to infections) and inflammation of the mouth. Some people have also experienced slow heart rate during paclitaxel infusion.
Docetaxel has a specific side effect of causing fluid retention in the body. This usually increases over time and is thought to be due to leaky blood vessels. Like paclitaxel, Docetaxel can also lower white blood cell count, especially with certain dosage schedules. The nerve damage is less severe with Docetaxel than with paclitaxel, possibly due to differences in their structure.
Nab-paclitaxel gets spread throughout the blood quite extensively because it is blended with albumin. Because of the higher accessibility and absorption in the body, it can be more effective than traditional paclitaxel. However, this may also lead to higher chances of experiencing side effects like lowered white blood cell count and nerve damage.
Risk Factors and Frequency for Taxane Toxicity
Earlier, about 30% of patients having treatments with paclitaxel and docetaxel experienced hypersensitivity reactions. But, the use of premedication has now reduced this number to around 1 to 2%. These reactions usually happened within the first 10 minutes of the first or second treatment and rarely happened after.
- Almost 30% of patients experienced a slower heart rate (bradycardia) with the use of paclitaxel.
- About 30 to 40% of patients experienced mouth sores (mucositis).
- Only 5 to 10% of patients experienced skin rash and nail damage (onycholysis).
- On the other hand, around 80% of patients had skin toxicity due to the use of docetaxel.
- Blood-related toxicity (hematologic toxicity) was noted as being very common, especially with cabazitaxel, with more than 90% of patients experiencing a decrease in white blood cells (neutropenia).
Signs and Symptoms of Taxane Toxicity
People may experience different types of reactions and side effects when taking certain drugs, commonly known as hypersensitivity reactions. These reactions can range from minor issues to serious health problems. Following are some of the common reactions:
- Minor reactions, experienced by about 40% of people, may manifest as skin irritations like hives or rashes.
- Major reactions can cause symptoms like nausea, vomiting, facial flushing, hives, breathing problems, wheezing, increased heart rate, low blood pressure, and pain in the abdomen or chest.
Neuropathy, or nerve pain, is another potential side effect of some drugs. It often feels like tingling or numbness in the hands and feet. Some patients may also experience muscle weakness or problems with bladder or bowel control. However, during a medical check-up, sensory loss is usually the most common finding.
Mucositis is a condition that can be caused by certain drugs (taxanes) and usually results in mouth ulcers, nausea, vomiting, and diarrhea.
Fluid retention is another issue which can particularly occur with the use of the drug Docetaxel. Symptoms include swelling in the feet and ankles, weight gain, bloating, breathing difficulty, and facial swelling.
Skin toxicity is a likely side effect of Docetaxel. Most patients experience mild skin inflammation, nail discoloration, and hair loss. However, serious toxicity can lead to hand and foot peeling, nail loss, and an excessive redness of the skin.
Bradycardia, or a slow heart rate, while benign, is the most common cardiac side effect found with the drug Paclitaxel.
Lastly, Ophthalmic toxicity, a rare side effect which affects 1 to 2% of individuals, can result in eye issues such as meibomian gland dysfunction, cystoid macular edema and canalicular obstruction. Despite these eye problems, treatment usually continues.
Testing for Taxane Toxicity
Every three weeks, doctors usually request a complete blood count and liver function tests when giving patients certain drug infusions. They do this to check for conditions like neutropenia (a low amount of white blood cells called neutrophils), thrombocytopenia (low platelet count), and increased liver enzymes which can all potentially be side effects of the treatment.
Although there isn’t a universal agreement on what routine blood tests should be done for weekly drug regimens, follow the guidance from your healthcare facility.
Interestingly, recent studies have suggested that certain genes may make people more susceptible to the toxicity from a class of drugs called taxanes. These drugs are broken down in the body by enzymes, known as Cytochrome P450 (specifically CYP3A4 and CYP3A5), into inactive compounds that are then removed from the body. In some rare cases (about 0.2% of people), there are variations in these enzymes that make them less effective at breaking down taxanes which leads to an accumulation of the drug in the body and increased toxicity. While other medications don’t seem to make this issue worse, certain genetic differences (such as in the SLCO1B3, ABCC2, or ABCB1 genes) may potentially increase the problem.
To determine if a patient might have an allergy to taxanes, doctors have found that taxane skin testing is a reliable technique. It can indicate if someone is likely to have an immediate allergic reaction (known as an IgE-mediated hypersensitivity reaction) to the drug.
If a doctor suspects a condition called neutropenic enterocolitis (an inflammation of the small intestine that can occur when there is a low neutrophil count), an abdominal ultrasound can help provide answers. This type of imaging test allows doctors to evaluate the thickness of the gut, which can give an indication of inflammation.
In case of nerve issues like neuropathy (a condition where nerves outside the brain and spinal cord have been damaged), doctors may perform nerve conduction studies. These tests record the speed of electrical signals moving through the nerves, and can help confirm nerve damage.
Treatment Options for Taxane Toxicity
Most side effects from taxane-based drugs, which are commonly used for cancer treatment, can be reversed if managed properly and on time. Both preventive measures and specific treatments can help lessen the impact of these side effects.
One common side effect is called hypersensitivity reactions, which can be reduced by use of preventive steroids and pre-drugs administered before the actual treatment. If severe hypersensitivity reactions occur, despite this preventive action, high-dose steroids are given immediately. For minor reactions, no medication is needed. If the reaction is life-threatening, adrenaline may be required. Future treatments with taxane drugs will depend on the severity of these reactions and may require a gradual reintroduction of the drug into the system.
Another side effect from taxane treatment is neurotoxicity, which affects the nerve cells and can result in conditions like neuropathy, often causing nerve pain that can be difficult to treat. Though there are no definitive cures, certain antidepressants and nerve pain drugs have been used to manage the pain. In some cases, local anesthetics and corticosteroids are combined with other drugs to help relieve neuropathic pain. A treatment method involving thermally-generated water cuffs, known as “hilotherapy,” that provide a constant temperature over an affected area has also been shown to have some success in treating taxane-induced nerve damage.
Neutropenia, a condition characterized by a low number of white blood cells called neutrophils, is a major side effect of taxane drugs. Its severity can limit the dosage of the drug. If a patient’s neutrophil count drops below a certain level, the drug must not be administered. Instead, measures are taken to increase the neutrophil count using certain growth factors. If patients have a fever as well as a low neutrophil count, they may need to be treated for a condition called ‘neutropenic sepsis’.
Steroids are also used to prevent fluid accumulation in the body, which can be a side effect of taxane therapy. In severe cases, medications that manage fluid levels may be used. Skin issues can also arise from this treatment, and depending on the severity, local treatments and specialist consultations may be advised.
Some patients experience a slowing of the heart rate as a side effect of this treatment, but it usually doesn’t require any medical intervention. Other patients might experience joint and muscle pain, which can be treated with certain non-opioid pain relievers.
What else can Taxane Toxicity be?
Hypersensitivity reactions can include a variety of conditions such as:
- Allergic sinusitis
- Hives, also known as urticaria
- Swelling under the skin, known as angioedema
- Severe allergic reactions due to food or environmental factors, known as anaphylaxis
- Anxiety disorder
- Blood clots in the lungs, known as pulmonary embolism
- Heart attack, also known as myocardial infarction
Neuropathy, or damage to the nerves, can be caused by conditions such as:
- Alcoholism
- High blood sugar, known as diabetes mellitus
- A type of anemia called pernicious anemia
- Lack of essential nutrients in diet
- Underactive thyroid, known as hypothyroidism
- Lyme disease
- HIV
Fluid retention can occur due to conditions like:
- Low levels of albumin in the blood, called hypoalbuminemia
- Heart failure, also known as congestive cardiac failure
- Chronic liver failure
- Long-term kidney disease, known as chronic kidney disease
What to expect with Taxane Toxicity
Although taxane, a type of medication, can often cause unwanted side effects, most people fully recover, except for a condition called neuropathy, which is damage to the nerves. This nerve damage can be permanent, particularly for individuals with diabetes or a history of alcohol misuse, as they are more likely to experience long-lasting harmful effects on their nerves.
However, quick and effective treatment of both the nerve damage and associated medical conditions can help avoid long-term damage or disability. So, it’s very important to manage these conditions promptly and efficiently.
Possible Complications When Diagnosed with Taxane Toxicity
Complications from taxane therapy that can’t be reversed are uncommon. However, when coupling doxorubicin and paclitaxel, there’s an increased chance of enduring congestive heart failure. There are also cases where taxanes, particularly docetaxel, have been linked to a skin condition similar to scleroderma.
Extended therapy use can also result in rare occurrences like pneumonitis. According to a recent study, other than a decreased count of neutrophils, which is a type of white blood cell, complications from Taxane treatments can generally be managed with precautionary medication, monitoring, and immediate care.
However, most healthcare providers are hesitant to stop a chemotherapy treatment that hugely benefits the patient due to a single incident.
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Complications from taxane therapy that can’t be reversed are uncommon. However, when coupling doxorubicin and paclitaxel, there’s an increased chance of enduring congestive heart failure. There are also cases where taxanes, particularly docetaxel, have been linked to a skin condition similar to scleroderma.
Extended therapy use can also result in rare occurrences like pneumonitis. According to a recent study, other than a decreased count of neutrophils, which is a type of white blood cell, complications from Taxane treatments can generally be managed with precautionary medication, monitoring, and immediate care.
However, most healthcare providers are hesitant to stop a chemotherapy treatment that hugely benefits the patient due to a single incident.
Preventing Taxane Toxicity
It’s important for patients to understand the potential side effects linked to a group of drugs called taxanes. There are a few ways patients can help protect themselves. For instance, consistently applying sunscreen and avoiding sun exposure can prevent skin inflammation caused by a specific drug called paclitaxel.
It’s crucial patients know how to recognize the signs of neutropenic fever, which is a fever that can happen when the body has a low number of a type of white blood cell called neutrophils. This knowledge enables them to seek prompt medical attention. Nurses specialized in chemotherapy and pharmacists play a key role in teaching patients and their families about these aspects.
Regular exercise can help reduce nerve pain, a condition known as neuropathy, so physiotherapists are well-positioned to assist in designing a consistent exercise schedule suited to the patient’s ability.
