Docetaxel - Indications, Dosage, and Contraindications

What Is Docetaxel?

Docetaxel is a Food and Drug Administration (FDA)-approved chemotherapy drug, which got its approval in 1996 and is used to treat various types of cancer. It is administered through an intravenous infusion. It inhibits cancer growth and the spread of cancer cells. Doctors use it alone for breast cancer that has not responded to chemotherapy, as well as for non-small cell lung cancer (NSCLC) after platinum-based treatment fails. Docetaxel injection can be used alone or with other drugs like Cisplatin, Fluorouracil, or Prednisone to increase its effectiveness.

What Is Docetaxel Used For?

Docetaxel is used for the treatment of the following cancers:

1. Docetaxel injection is used for breast cancer that is spreading locally and aggressively. In such cases, chemotherapy fails.

2. In some cases of locally and aggressively advancing non-small cell lung cancer (NSCLC), platinum therapy or Cisplatin fails. Doctors use Docetaxel injection in such cases.

3. Doctors use it to treat Docetaxel along with Prednisone in androgen-independent metastatic prostate cancer. Such cases belong to hormone-refractory prostate cancer (HRPC).

4. Doctors use Docetaxel injection along with Cisplatin and Fluorouracil for untreated, advanced gastric adenocarcinoma.

5. Docetaxel injection is used along with Cisplatin and Fluorouracil for the induction of locally advanced squamous cell carcinoma of the head and neck.

How Does Docetaxel Work?

Docetaxel is a taxane drug that kills cancer cells. It is made from yew plants.

Docetaxel disrupts the internal structure of the cell, called microtubules. These are necessary for cell division and growth. Docetaxel hampers the functioning of microtubules. This prevents cancer cell division and growth. As a result, cancer cells die. Docetaxel prevents cancer cells from dividing and causes them to die. This makes it an effective treatment for slowing down or stopping the spread of cancer.

What Is the Dosage and Administration Protocol for Docetaxel?

Docetaxel injections are available in the form of injections that are delivered into the veins (intravenously) by a doctor or healthcare professional.

• It is usually delivered once every three weeks for one hour.

• The doctor aseptically takes the required amount of Docetaxel injection solution (10 milligrams per milliliter) from the syringe and injects it into 250 ml infusion bags or bottles selected, using either Sodium chloride 0.9 percent solution or Dextrose 5 percent to form a final solution of 0.3 to 0.74 milligrams per milliliter.

• If the dose is greater than 200 mg of Docetaxel, then a larger volume of infusion bag should be used with a concentration of 0.74 milligrams per milliliter.

The doctor will give a premedication of corticosteroids, such as Dexamethasone, to prevent adverse effects, and it is usually taken before each dose cycle.

Docetaxel is based on the patient's body surface area (square meter or m2). The dose may vary based on cases,

1. In hormone-refractory prostate cancer cases, 75 milligrams (mg)/ m2 with 5 mg of Prednisone is given twice daily.

2. In gastric adenocarcinoma and squamous cell carcinoma of the head and neck cancer, the use of 75 mg/m2 followed by Cisplatin 75 mg/m2 administered both on day one, followed by Fluorouracil 750 mg/m2 per day for 24 hours infusion for five days, with the end of Cisplatin infusion for four cycles.

3. If the breast cancer is spreading locally, doctors give a 60 mg/m2 to 100 mg/m2 dose of Docetaxel for one hour every three weeks.

4. It is also administered at 75 mg/m2 following a Cisplatin 100 mg/m2 injection in cases of NSCLC.

5. For head and neck cancer, Docetaxel is given at 75 mg/m2 as a one-hour intravenous infusion, followed by Cisplatin 75 mg/m2 over one hour, on the first day after Fluorouracil 750 mg/m2 for five days. It is repeated every three weeks for four cycles. For the patients who have undergone chemoradiotherapy, a 75 mg/m2 Docetaxel dose on day one, followed by Cisplatin, which is given 100 mg/m2 in 30 minutes to three hours, followed by Fluorouracil 1000 mg/m2 per day from day one to four, which is repeated every three weeks for three cycles.

Liver enzymes CYP3A4 and cytochrome P4503A4 help to metabolize this medicine. As a result, medications that affect these liver enzymes may require dose modification of Docetaxel. These medicines include Ketoconazole, Itraconazole, Clarithromycin, Atazanavir, Telithromycin, and Voriconazole. Also, if the patient has liver issues, doctors may reduce the dose.

People with low neutrophil counts (neutropenia) or other blood count abnormalities (low white blood cells, platelets, or red blood cells) should not take this.

What Are the Dosage Adjustments During Treatment?

• Breast Cancer:

Patients who receive 100 mg/m2 may develop neutropenia (less than 500 neutrophils) for more than 1 week; the dosage is then adjusted from 100 to 75 mg/m2. If the patient carries these symptoms further, the dose is reduced to 75-55 mg/m2. If the patient develops more than grade three peripheral neuropathy, then discontinuation of the drug has to be done.

• Combination Therapy in Breast Cancers:

If the patient is co-administered Docetaxel with Doxorubicin and Cyclophosphamide, the neutrophil count can be more than 1500 cells per milliliter or three to four stomatitis. In such cases, the Docetaxel dosage should be reduced to 60 mg/m2.

• Non-Small Cell Lung Cancer:

In Docetaxel monotherapy, the patient develops neutropenia, so the dose is reduced to 55 milligrams per square meter. In combination therapy, the Cisplatin dose is reduced from 65 mg/m2 to 50 mg/m2.

• Prostate Cancer:

Docetaxel injections are reduced from 75 to 60 mg/m2. If the patient continues to face a reaction, it has to be discontinued at last.

• Gastric Cancer and Head and Neck Cancer:

Patients who have received Docetaxel in combination with Cisplatin and Fluorouracil for gastric cancers or head and neck cancers are observed for neutropenia lasting for a week. If the febrile neutropenia episodes are becoming severe, the injection is reduced to 60 mg/m2. Further discontinuing the treatment has to be suggested if toxic results persist.

For Patients:

What Docetaxel Precautions Should I Follow?

• Inform the doctor in case of any allergic reactions to Docetaxel.

• Tell your doctor about all the other medications you are taking.

• The patient should avoid the use of alcohol while being on Docetaxel injection.

• Avoid being pregnant during Docetaxel treatment.

• The patient should not breastfeed while taking Docetaxel injection and for two weeks after the final dose.

• Inform your doctor before undergoing any surgery, including dental procedures.

• Docetaxel can cause drowsiness and affect thinking and motor functions. So, the patient should avoid driving and other tasks requiring concentration.

What Are the Side Effects of Docetaxel?

The Docetaxel side effects can vary, and some common symptoms include:

1. Vomiting.

2. Constipation.

3. Changes in taste.

4. Extreme tiredness.

5. Muscle, joint, or bone pain.

6. Loss of hair.

7. Changes in nails.

8. Eye tearing is increasing.

9. Sores in the mouth and throat.

10. Redness, dryness, or swelling at the site of injection.

In some cases, serious Docetaxel side effects may occur, requiring immediate medical attention. These severe reactions can include:

1. Blister on the skin.

2. Numbness and tingling in the hands and feet.

3. Burning sensation in hands and feet.

4. Weakness in the hands and feet.

5. Unusual bleeding or bruising.

6. Nose bleeding.

7. Blurred vision.

8. Loss of vision.

9. Stomach pain.

10. Tenderness.

11. Diarrhea.

12. Fever.

For Doctors:

What Are Preparations for the Administration of Docetaxel?

The use of Docetaxel injection at 10 mg per milliliter does not require prior dilution with a diluent; it is ready to be added to the infusion solution for infusion.

Infusion:

• The doctor aseptically takes the required amount of Docetaxel injection solution (10 milligrams per milliliter) from the syringe and injects it into 250 ml infusion bags or bottles selected, using either Sodium chloride 0.9 percent solution or Dextrose 5 percent to form a final solution of 0.3 to 0.74 mg per milliliter.

• If the dose is greater than 200 mg of Docetaxel, then a larger volume of infusion bag should be used with a concentration of 0.74 milligrams per milliliter.

• Mix the infusion bag or bottle thoroughly by inverting or rotating it in a controlled manner, avoiding foaming. Shaking is also prevented during preparation and transportation.

• Docetaxel injection is visually inspected before administration; if the diluted solution is not clear or contains precipitation, it must be discarded.

• The solution is infused intravenously for 1 hour at ambient room temperature, below 25 degrees Celsius.

• It is stored between 2 degrees Celsius and 25 degrees Celsius for stability. It remains stable for 4 hours in 0.9% sodium chloride or 5% dextrose. It should be used within four hours. It should not be frozen.

What Is the Pharmacology of Docetaxel?

• Absorption:

Docetaxel is administered intravenously. An infusion takes one to two hours. It has a three-compartment bag with half-lives of 4 minutes for alpha, 36 minutes for beta, and 11.1 hours for gamma. Total clearance was 21 liters per hour per square meter.

• Elimination:

Docetaxel is eliminated in urine and feces, with the main route of elimination via stool. In the seven days, urinary excretion is seven percent, and fecal excretion is 75 percent. Nearly 80 percent is excreted during 48 hours as one major and three minor metabolites are formed.

What Are the Risks of Docetaxel Treatment?

If a patient is receiving Docetaxel treatment, the following risks may occur;

1. Acute Myeloid Leukemia:

Docetaxel, Doxorubicin, and Cyclophosphamide can affect the normal function of your bone marrow. Delayed myelodysplasia or myeloid leukemia can happen due to suppression of the bone marrow. This can cause patients to suffer from anemia or a low platelet count.

2. Sepsis:

In severe cases, Docetaxel can cause a massive drop in neutrophil count. This can lower the body's defense mechanism. As a result, the patient may face severe infection and sepsis.

3. Cutaneous and Skin Reactions:

The use of Docetaxel can cause reactions, including severe redness and swelling of the skin. If severe skin toxicity occurs, such as peeling off the skin, then it requires immediate attention. For patients suffering from severe hypersensitivity reactions with symptoms like Docetaxel rash, erythema, hypotension, or bronchospasm in the first or second dose or within three days of corticosteroids, discontinuation of the drug is an option.

4. Neurologic Reactions:

Nerve damage due to Docetaxel can cause abnormal neural sensations. Also, it can cause the absence of nerve sensation in some parts of the body.

5. Pregnancy:

If the patient is pregnant, Docetaxel is not used because it can cause fetal harm. It can even cause the death of the unborn baby.

6. Fluid Retention:

Docetaxel therapy can cause fluid accumulation in the body. It can lead to swelling in various parts of the body, such as the abdomen, face, and ankles. If the condition is severe, it can damage the kidneys and liver. Steroid premedications can prevent it.

Conclusion

Docetaxel is an FDA-approved anti-cancer medicine. This chemotherapeutic medicine can effectively treat breast cancer, non-small cell lung cancer, head and neck cancer, and pancreatic cancer. As a taxane group of drugs, they can prevent the growth and spread of cancer cells by disrupting the functionality of microtubules. However, it can cause moderate to severe side effects like diarrhea, fever, weakness, and vomiting. If you have further queries, you can consult a cancer specialist for proper guidance.

Key Takeaways

1. Docetaxel is a taxane drug.

2. It kills cancer cells by hampering the functioning of microtubules.

3. This chemotherapeutic medicine can effectively treat breast cancer, non-small cell lung cancer, head and neck cancer, and pancreatic cancer.

4. Its side effects include diarrhea, fever, weakness, and vomiting.