Docetaxel

Docetaxel is a chemotherapy drug that is 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 intravenously as an infusion, often in combination with other chemotherapy drugs or targeted therapies.

In addition to treating cancer, docetaxel may also be used to treat other diseases such as sarcoidosis or immune system disorders, but these are less common uses and require careful prescribing 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 failed.
4. Ovarian cancer: It can be used in combination with other drugs to treat different types of ovarian cancer.
5. Other cancers: Docetaxel may also be used in the treatment of bladder, brain, cervical, esophageal, gastric, liver, pancreatic, and other cancers in certain clinical scenarios.

Release form

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

The drug is presented in bottles 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, which leads to the 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 of the drug, it reaches peak concentration in the blood after about 1 hour.
2. Distribution: Docetaxel is highly bound to plasma proteins (more than 94%). It is distributed to various tissues of the body, including tumors.
3. Metabolism: Docetaxel is primarily metabolized in the liver via cytochrome P450. The main metabolite is 4-hydroxy-docetaxel.
4. Half-life: The half-life of docetaxel from the body varies widely and usually ranges from 11 to 25 hours.
5. Excretion: About 75% of docetaxel is excreted from the body through bile in the form of metabolites, approximately 5-20% is excreted unchanged in the urine.
6. Systemic concentration: After intravenous administration of docetaxel, the concentration in the blood decreases in a two-phase manner.

Dosing and administration

Method of application:

• The drug is intended for intravenous administration (infusion).
• 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 drugs.

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

Premedication:

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

Use Docetaxel during pregnancy

The use of Docetaxel during pregnancy requires an assessment of potential risks and benefits. Here are some key points based on scientific research:

1. Changes in pharmacokinetics during pregnancy: Physiological changes during pregnancy may affect the pharmacokinetics of Docetaxel, potentially reducing its effectiveness and safety. Some studies indicate that the clearance of Docetaxel may be increased, 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 malignant neoplasms. The results indicate that treatment may be relatively safe for the fetus under certain conditions and strict medical supervision (Nieto et al., 2006).
3. Recommendations for treatment: Despite some positive data, the use of Docetaxel during pregnancy should be 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 your oncologist to evaluate all risks and possible treatment alternatives.

Contraindications

1. Allergy: People with a known hypersensitivity or allergy to docetaxel or any other component of the drug should avoid using it.
2. Low blood protein (lymphocytopenia): Docetaxel can cause a decrease in the amount of proteins in the blood, such as lymphocytes. Therefore, the drug may be contraindicated in patients with already low blood protein levels.
3. Severe liver damage: Because the liver plays an important role in the metabolism of docetaxel, its use may be contraindicated in patients with severe hepatic impairment.
4. Pregnancy: The use of docetaxel is not recommended during pregnancy due to potential harmful effects on the fetus.
5. Breastfeeding: Similar to pregnancy, the use of docetaxel is not recommended during breastfeeding due to risks to the baby.
6. Severe Infections: Patients with severe infections or sepsis may have an increased risk of complications from docetaxel.
7. Severe allopenia: Docetaxel may have a toxic effect on the bone marrow, leading to the development of allopenia (decreased number of hematopoietic 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 counts), docetaxel may be contraindicated due to the increased risk of infections.

Side effects Docetaxel

1. Hematological disorders: Blood levels may decrease, which can lead to anemia, thrombocytopenia (low platelet count) and leukopenia (low white blood cell count).
2. Weakened immune system: This may 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 renal function.
8. Liver dysfunction: Elevated liver enzymes and jaundice may occur.
9. Shortness of breath: Trouble breathing may occur.
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 lead to increased toxic effects of the drug, such as hematological disorders (for example, 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 a decrease in the number of white blood cells, platelets and red blood cells in the blood.
3. Neurotoxicity: Overdose may increase neurotoxicity manifested as peripheral neuropathy (similar to diabetic neuropathy), which causes 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 use with other drugs that also affect hematopoiesis, such as cytostatics, may increase the risk of these side effects.
2. Drugs that affect the liver: Because docetaxel is metabolized in the liver, drugs that affect liver function may alter its metabolism and blood levels. This includes drugs such as liver enzyme inhibitors or inducers, as well as drugs that cause hepatotoxicity.
3. Drugs affecting the cytochrome P450 system: Docetaxel is metabolized by cytochrome P450 in the liver. Therefore, drugs that are inhibitors or inducers of this enzyme may alter the blood concentration of docetaxel 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 affecting acid-base balance: Docetaxel can 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.