Paclitaxel is a chemotherapy drug that is given as a treatment for some types of cancer. It is commonly known as Taxol. It is most commonly used to treat ovarian, breast and lung cancer. This information describes paclitaxel, how it is given and some of its possible side effects.

What Taxol looks like

Taxol is a colourless fluid.

How it is given

Taxol may be given as a drip (infusion):

• through a fine tube (cannula) inserted into the vein
• through a central line (Hickman or Portacath), which is inserted under the skin into a vein near the collarbone, or into a PICC, which is inserted into a vein in the crook of the arm.
• Taxol is most commonly given as a 3 hour infusion.

Chemotherapy is usually given as a course of several sessions (or cycles) of treatment over a few months. The length of your treatment and the number of cycles you have will depend on the type of cancer for which you are being treated. Your nurse or doctor will discuss your treatment plan with you.

Possible side effects

Each person’s reaction to chemotherapy is different. Some people have very few side effects, while others may experience more. The side effects described in this information will not affect everyone who is given Taxol, and may be different if you are having more than one chemotherapy drug.

We have outlined the most common side effects as well as rarer ones, so that you can be aware of them if they occur. However, we have not included those that are very rare and therefore extremely unlikely to affect you. If you do notice any effects which you think may be due to the drug, but which are not listed in this information, please discuss these with your doctor or chemotherapy nurse.

Lowered resistance to infection

Taxol can reduce the production of white blood cells by the bone marrow, making you more prone to infection. This effect can begin seven days after treatment has been given and your resistance to infection usually reaches its lowest point 10–14 days after chemotherapy. Your blood cells will then increase steadily and will usually have returned to normal levels before your next cycle of chemotherapy is due.

Contact your doctor or the hospital straightaway if:

• your temperature goes above 38ºC (100.5ºF)
• you suddenly feel unwell (even with a normal temperature).

You will have a blood test before having more chemotherapy, to make sure that your cells have recovered. Occasionally it may be necessary to delay your treatment if the number of blood cells (the blood count) is still low.

Bruising or bleeding

Taxol can reduce the production of platelets (which help the blood to clot). Let your doctor know if you have any unexplained bruising or bleeding, such as nosebleeds, blood spots or rashes on the skin, and bleeding gums. Your platelet count will be checked prior to each cycle of treatment.

Anaemia (low number of red blood cells)

While having treatment with Taxol you may become anaemic. This may make you feel tired and breathless. Let your doctor or nurse know if these symptoms are a problem.

Sore mouth and ulcers

Your mouth may become sore, or you may notice small ulcers during this treatment. Drinking plenty of fluids, and cleaning your teeth regularly and gently with a soft toothbrush, can help to reduce the risk of this happening. Tell your nurse or doctor if you have any of these problems, as they can prescribe special mouthwashes and medicines to prevent or clear any mouth infection.

Taste changes

You may notice that your food tastes different. Normal taste will usually come back after the treatment finishes.

Diarrhoea

This can usually be easily controlled with medicines such as loperamide or codeine but let your doctor know if it is severe or if it continues. It is important to drink plenty of fluids if you do have diarrhoea.

Tiredness and feeling weak

You may feel very tired. It is important to allow yourself plenty of time to rest.

Hair loss

Most patients lose their hair with Taxol. This usually starts 2–3 weeks after the first dose of Taxol, although it may happen earlier. All of your hair will usually fall out completely, but it may just thin. You may also have thinning and loss of eyelashes, eyebrows and other body hair. Hair loss is temporary and your hair will regrow once the treatment is finished. To help reduce hair loss, scalp cooling may be suitable for some people.

Aching or pain in joints and muscles

This may occur a few days after Taxol is given. It does not usually last long and your doctor may prescribe painkillers or anti-inflammatory drugs to help.

Skin changes

Taxol can cause a rash, which may be itchy. Your doctor can prescribe medicine to help with this.

Numbness or tingling in hands or feet.

This is due to the effect of Taxol on nerves and is known as peripheral neuropathy. You may also notice that you have difficulty doing up buttons or similar fiddly tasks. Tell your doctor if you notice any numbness or tingling in your hands or feet. This usually improves slowly a few months after the treatment is finished.

Headaches

Some people find that Taxol causes headaches. Let your doctor know if you have headaches while having treatment.

Allergic reaction

Signs of an allergic reaction include skin rashes and itching, a high temperature, shivering, redness of the face, a feeling of dizziness, headache, breathlessness, anxiety and a desire to pass urine. You will be monitored for any signs of an allergic reaction during the treatment. Tell your doctor or nurse if you have any of these signs.

You will be given steroid tablets (usually dexamethasone) to take before the Taxol to reduce the chance of an allergic reaction. If you are given any of these tablets before treatment it is important to take them as directed and to tell your doctor or nurse if you forget.

Feeling sick (nausea) and being sick (vomiting)

If you do feel sick this may begin soon after the treatment is given and last for a few days. Your doctor can prescribe very effective anti-sickness (anti-emetic) drugs to prevent, or greatly reduce, nausea. If the sickness is not controlled, or continues, tell your doctor; they can prescribe other anti-sickness drugs which may be more effective. Some anti-sickness drugs can cause constipation. Let your doctor or nurse know if this is a problem.

Less common side effects

Low blood pressure

Your blood pressure will be checked regularly during treatment. Let your doctor know if you feel faint or dizzy.

Changes in heart rate

Taxol can sometimes cause a temporary slowing of the heart rate known as bradycardia. This usually does not cause any harm.

Your liver may be temporarily affected

Taxol may cause changes in the way that your liver works, though your liver will return to normal when the treatment is finished. This is very unlikely to cause you any harm, but your doctor will monitor this carefully. Samples of your blood will be taken from time to time to check your liver is working properly.

Abdominal pain

This may start a few days after finishing the chemotherapy and may last for a few days. Your doctor can prescribe regular painkillers if it does happen.

Additional information

Injection site

While Taxol is being given, it can cause pain at the place where the injection is given, or along the vein. If you feel pain, tell your doctor or nurse. They can slow the drip down to reduce the feeling.

Risk of blood clots

Cancer can increase your risk of developing a blood clot (thrombosis), and having chemotherapy may increase this risk further. A blood clot may cause symptoms such as pain, redness and swelling in a leg, or breathlessness and chest pain. Blood clots can be very serious so it is important to tell your doctor straightaway if you have any of these symptoms. However, most clots can usually be successfully treated with drugs to thin the blood. Your doctor or nurse can give you more information.

Other medicines

Some medicines can be harmful to take when you are having chemotherapy. Let your doctor know about any medications you are taking, including non-prescribed drugs such as complementary therapies and herbal drugs.

Fertility

Your ability to become pregnant or father a child may be affected by taking this drug. It is important to discuss fertility with your doctor before starting treatment.

Contraception

It is not advisable to become pregnant or father a child while taking Taxol, as the developing foetus may be harmed. It is important to use effective contraception while taking this drug, and for at least a few months afterwards. Again, discuss this with your doctor.

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Additional Information For Healthcare Professionals

ADVERSE REACTIONS SIGNIFICANT

Percentages reported with single-agent therapy. Note: Myelosuppression is dose related, schedule related, and infusion-rate dependent (increased incidences with higher doses, more frequent doses, and longer infusion times) and, in general, rapidly reversible upon discontinuation.

>10%:

• Cardiovascular: Flushing (28%), ECG abnormal (14% to 23%), edema (21%), hypotension (4% to 12%)
• Dermatologic: Alopecia (87%), rash (12%)
• Gastrointestinal: Nausea/vomiting (52%), diarrhea (38%), mucositis (17% to 35%; grades 3/4: up to 3%), stomatitis (15%; most common at doses >390 mg/m2), abdominal pain (with intraperitoneal paclitaxel)
• Hematologic: Neutropenia (78% to 98%; grade 4: 14% to 75%; onset 8-10 days, median nadir 11 days, recovery 15-21 days), leukopenia (90%; grade 4: 17%), anemia (47% to 90%; grades 3/4: 2% to 16%), thrombocytopenia (4% to 20%; grades 3/4: 1% to 7%), bleeding (14%)
• Hepatic: Alkaline phosphatase increased (22%), AST increased (19%)
• Local: Injection site reaction (erythema, tenderness, skin discoloration, swelling: 13%)
• Neuromuscular & skeletal: Peripheral neuropathy (42% to 70%; grades 3/4: up to 7%), arthralgia/myalgia (60%), weakness (17%)
• Renal: Creatinine increased (observed in KS patients only: 18% to 34%; severe: 5% to 7%)
• Miscellaneous: Hypersensitivity reaction (31% to 45%; grades 3/4: up to 2%), infection (15% to 30%)

1% to 10%:

• Cardiovascular: Bradycardia (3%), tachycardia (2%), hypertension (1%), rhythm abnormalities (1%), syncope (1%), venous thrombosis (1%)
• Dermatologic: Nail changes (2%)
• Hematologic: Febrile neutropenia (2%)
• Hepatic: Bilirubin increased (7%)
• Respiratory: Dyspnea (2%)

<1% (Limited to important or life-threatening):

Anaphylaxis, ataxia, atrial fibrillation, AV block, back pain, cardiac conduction abnormalities, cellulitis, CHF, chills, conjunctivitis, dehydration, enterocolitis, extravasation recall, hepatic encephalopathy, hepatic necrosis, induration, intestinal obstruction, intestinal perforation, interstitial pneumonia, ischemic colitis, lacrimation increased, maculopapular rash, malaise, MI, necrotic changes and ulceration following extravasation, neuroencephalopathy, neutropenic enterocolitis, ototoxicity (tinnitus and hearing loss), pancreatitis, paralytic ileus, phlebitis, pruritus, pulmonary embolism, pulmonary fibrosis, radiation recall, radiation pneumonitis, pruritus, renal insufficiency, seizure, skin exfoliation, skin fibrosis, skin necrosis, Stevens-Johnson syndrome, supraventricular tachycardia, toxic epidermal necrolysis, ventricular tachycardia (asymptomatic), visual disturbances (scintillating scotomata)

MECHANISM OF ACTION

Paclitaxel promotes microtubule assembly by enhancing the action of tubulin dimers, stabilizing existing microtubules, and inhibiting their disassembly, interfering with the late G2 mitotic phase, and inhibiting cell replication. In addition, the drug can distort mitotic spindles, resulting in the breakage of chromosomes. Paclitaxel may also suppress cell proliferation and modulate immune response.

PHARMACODYNAMICS / KINETICS

Distribution:

• Vd: Widely distributed into body fluids and tissues; affected by dose and duration of infusion
• Vdss:
  • 1- to 6-hour infusion: 67.1 L/m2
  • 24-hour infusion: 227-688 L/m2
• Protein binding: 89% to 98%
• Metabolism: Hepatic via CYP2C8 and 3A4; forms metabolites (primarily 6alpha-hydroxypaclitaxel)
• Half-life elimination:
  • 1- to 6-hour infusion: Mean (beta): 6.4 hours
  • 3-hour infusion: Mean (terminal): 13.1-20.2 hours
  • 24-hour infusion: Mean (terminal): 15.7-52.7 hours
• Excretion: Faeces (~70%, 5% as unchanged drug); urine (14%)
• Clearance: Mean: Total body: After 1- and 6-hour infusions: 5.8-16.3 L/hour/m2; After 24-hour infusions: 14.2-17.2 L/hour/m2