Docetaxel

Docetaxel is a chemotherapy drug used to treat various types of cancer. It belongs to a class of drugs known as taxanes. Docetaxel works by blocking the ability of cancer cells to divide and grow, which helps slow or stop tumor growth.

This drug is commonly used as a treatment for breast cancer, lung cancer, prostate cancer, ovarian cancer and other forms of cancer. Docetaxel is usually given as an intravenous infusion, often in combination with other chemotherapy drugs or targeted therapy.

In addition to treating cancer, docetaxel may also be used to treat other conditions such as sarcoidosis or immune system disorders, but this is a less common use and requires careful prescription and monitoring by a physician.

Indications Docetaxel

1. Breast cancer: Docetaxel may be used in combination with other chemotherapy drugs to treat metastatic or recurrent breast cancer.
2. Lung cancer: It may be prescribed as a treatment for primary or metastatic lung cancer, either alone or in combination with other drugs.
3. Prostate cancer: Docetaxel may be used to treat metastatic prostate cancer in men, especially when other treatments have not been effective.
4. Ovarian cancer: It may be used in combination with other drugs to treat different types of ovarian cancer.
5. Other cancers: Docetaxel may also be used to treat bladder, brain, cervix, esophagus, stomach, liver, pancreas, and other cancers in certain clinical scenarios.

Release form

Docetaxel is available as a concentrate for the preparation of a solution for infusion.

The drug is available in vials of various sizes, which contain a concentrate intended for dilution before intravenous administration.

Pharmacodynamics

1. Mechanism of action:

   • Docetaxel belongs to a group of drugs called taxanes. It is a microtubule-binding agent that interferes with the normal function of microtubules.
   • Microtubules are important components of the cell cytoskeleton and are involved in cell division processes.
   • Docetaxel binds to beta-tubulin, resulting in stabilization of microtubules, inhibiting their dynamic instability.
   • This leads to disruption of mitotic (cell) division, as well as apoptosis (programmed cell death) of cancer cells.

Pharmacokinetics

1. Absorption: Docetaxel is usually administered intravenously. After administration, the drug reaches peak concentrations in the blood in about 1 hour.
2. Distribution: Docetaxel is highly bound to plasma proteins (more than 94%). It is distributed into various tissues of the body, including tumors.
3. Metabolism: Docetaxel is primarily metabolized in the liver via cytochrome P450. The major metabolite is 4-hydroxydocetaxel.
4. Elimination half-life: The elimination half-life of docetaxel in the body has a wide range and typically ranges from 11 to 25 hours.
5. Excretion: About 75% of docetaxel is excreted from the body via bile as metabolites, approximately 5-20% is excreted in urine unchanged.
6. Systemic concentration: Following intravenous administration of docetaxel, blood concentrations decrease in a biphasic manner.

Dosing and administration

Directions for use:

• The drug is intended for intravenous administration (infusions).
• The concentrate must be diluted before use in accordance with the instructions provided by the manufacturer.

Dosage:

Breast cancer:

• For adjuvant therapy: the recommended dose is 75 mg/m² in combination with doxorubicin and cyclophosphamide every 3 weeks for 6 cycles.
• For metastatic breast cancer: the dose is 100 mg/m² every 3 weeks as monotherapy or in combination with capecitabine.

Lung cancer:

• The recommended dose is 75 mg/m² administered every 3 weeks in combination with platinum-based agents.

Prostate cancer:

• The recommended dose is 75 mg/m² every 3 weeks in combination with prednisone or prednisolone.

Stomach cancer:

• The recommended dose is 75 mg/m² every 3 weeks in combination with cisplatin and fluorouracil.

Head and Neck Cancer:

• Induction therapy: the dose is 75 mg/m² in combination with cisplatin and fluorouracil every 3 weeks for 4 cycles.

Premedication:

• Patients are advised to premedicate with glucocorticosteroids to reduce the risk of hypersensitivity and to decrease fluid retention. Dexamethasone 16 mg daily (8 mg twice daily) for 3 days, starting the day before docetaxel administration, is usually prescribed.

Use Docetaxel during pregnancy

The use of Docetaxel during pregnancy involves weighing the potential risks and benefits. Here are some key points based on scientific research:

1. Pharmacokinetic changes during pregnancy: Physiological changes during pregnancy may affect the pharmacokinetics of Docetaxel, potentially reducing its efficacy and safety. Some studies suggest that Docetaxel clearance may increase, requiring dose adjustment (Janssen et al., 2021).
2. Safety of use: Studies have reported cases of successful use of Docetaxel in the second and third trimesters of pregnancy for breast cancer and other malignancies. The results indicate that the treatment may be relatively safe for the fetus if certain conditions are met and there is strict medical supervision (Nieto et al., 2006).
3. Treatment recommendations: Despite some positive data, the use of Docetaxel during pregnancy should be carried out under strict medical supervision, taking into account the individual clinical situation. It is important to weigh the potential benefit to the mother against the possible risk to the developing fetus.

Docetaxel can be used during pregnancy, but only under strict indications and under close medical supervision, especially in the second and third trimesters. You should always consult with an oncologist to assess all the risks and possible alternatives to therapy.

Contraindications

1. Allergy: People with known hypersensitivity or allergy to docetaxel or any other component of the drug should avoid using it.
2. Low blood protein levels (lymphocytopenia): Docetaxel may cause a decrease in the amount of proteins in the blood, such as lymphocytes. Therefore, the drug may not be used in patients who already have low blood protein levels.
3. Severe liver impairment: Since the liver plays an important role in the metabolism of docetaxel, its use may be contraindicated in patients with severe liver impairment.
4. Pregnancy: The use of docetaxel is not recommended during pregnancy due to potential harmful effects on the fetus.
5. Breastfeeding period: As with pregnancy, the use of docetaxel is not recommended during breastfeeding due to the risks to the child.
6. Severe infections: Patients with severe infections or sepsis may have an increased risk of complications from docetaxel.
7. Severe allopenia: Docetaxel may have toxic effects on the bone marrow, leading to the development of allopenia (a decrease in the number of blood-forming cells), so the use of the drug may be contraindicated in patients with severe allopenia.
8. Severe neutropenia: In patients with severe neutropenia (decreased neutrophil count), docetaxel may be contraindicated due to an increased risk of infections.

Side effects Docetaxel

1. Hematological disorders: Blood levels may decrease, which can lead to anemia, thrombocytopenia (decreased platelet count), and leukopenia (decreased white blood cell count).
2. Weakened immune system: This can lead to an increased risk of infections.
3. Obesity: Patients receiving Docetaxel may gain weight.
4. Skin changes: Rash, skin redness, dryness and itching may occur.
5. Hair loss: Complete or partial hair loss (alopecia) is a common side effect.
6. Nerve toxicity: This may include diarrhea, nausea, vomiting, muscle or joint pain, and numbness or tingling in the arms or legs.
7. Increased levels of urea and creatinine in the blood: This may indicate impaired kidney function.
8. Liver dysfunction: Increased liver enzymes and jaundice may occur.
9. Shortness of breath: You may have trouble breathing.
10. General malaise: Includes fatigue and weakness.
11. Other rare side effects: Include abdominal pain, cold leg syndrome, and others.

Overdose

1. Increased toxic effects: Overdose may result in increased toxic effects of the drug, such as hematological abnormalities (eg, severe neutropenia or thrombocytopenia), nausea, vomiting, diarrhea, and other side effects.
2. Bone marrow suppression: Docetaxel may suppress bone marrow function, which may result in decreased numbers of white blood cells, platelets, and red blood cells in the blood.
3. Neurotoxicity: Overdose may increase neurotoxicity, which manifests as peripheral neuropathy (similar to diabetic neuropathy), which is characterized by pain, numbness, and weakness in the extremities.

Interactions with other drugs

1. Drugs that increase hematological side effects: Docetaxel may increase hematological side effects such as leukopenia and thrombocytopenia. Therefore, concomitant administration with other drugs that also affect hematopoiesis, such as cytostatics, may increase the risk of these side effects.
2. Drugs that affect the liver: Since docetaxel is metabolized in the liver, drugs that affect liver function may alter its metabolism and blood levels. This includes drugs such as inhibitors or inducers of liver enzymes, as well as drugs that cause hepatotoxicity.
3. Drugs that affect the cytochrome P450 system: Docetaxel is metabolized by cytochrome P450 in the liver. Therefore, drugs that are inhibitors or inducers of this enzyme may change the concentration of docetaxel in the blood and its effectiveness.
4. Drugs that increase neurotoxicity: Docetaxel may cause neurotoxicity such as peripheral neuropathy. Concomitant use with other drugs that may also cause or increase this side effect, such as vincristine, may increase the risk of neuropathy.
5. Drugs that affect the immune system: Docetaxel may reduce immunity and increase the risk of infections. Concomitant use with drugs that also suppress the immune system, such as glucocorticoids or immunosuppressants, may increase this risk.
6. Drugs that affect acid-base balance: Docetaxel may cause hypokalemia and hypomagnesemia. Concomitant use with drugs such as diuretics or other drugs that can also affect potassium and magnesium levels in the body may increase these side effects.