Docetaxel is a chemotherapy agent belonging to the taxane class. It works by stabilizing microtubules and preventing their disassembly, which disrupts the mitotic spindle and blocks cell division during the mitotic phase of the cell cycle. This inhibition of cell division results in cell cycle arrest and apoptosis (cell death), particularly in rapidly dividing cancer cells.

1. Indications:

Docetaxel is used in the treatment of a variety of cancers, including:

1. Breast cancer: For both adjuvant and metastatic breast cancer, often in combination with other agents.
2. Non-small cell lung cancer (NSCLC): For advanced or metastatic NSCLC, typically in combination with cisplatin.
3. Prostate cancer: In combination with prednisone for metastatic hormone-refractory prostate cancer.
4. Head and neck cancers: For locally advanced or metastatic head and neck squamous cell carcinoma.
5. Gastric cancer: For metastatic or advanced gastric adenocarcinoma in combination with cisplatin.

2. Dosage and Administration:

Dosage Regimens:

• Breast Cancer (Metastatic):
  • The usual dose is 75-100 mg/m² IV over 1 hour every 3 weeks.
• Non-Small Cell Lung Cancer (NSCLC):
  • Typical dose: 75 mg/m² IV every 3 weeks, often in combination with cisplatin.
• Prostate Cancer (Metastatic, Hormone-Refractory):
  • The standard dose is 75 mg/m² IV every 3 weeks, combined with prednisone.
• Head and Neck Cancer:
  • Administered at 75 mg/m² every 3 weeks in combination with other chemotherapy agents.
• Gastric Cancer:
  • The typical dose is 75 mg/m² IV every 3 weeks, in combination with cisplatin.

3. Administration:

• Intravenous (IV) infusion only.
• Ready-to-use formulation (RTU): Docetaxel injection is available as a ready-to-use formulation in a solvent and does not require further dilution.
• Infusion Rate: Docetaxel should be infused over 1 hour.
• Premedication: Patients are often premedicated with corticosteroids (such as dexamethasone) for 3 days (starting 1 day before infusion) to reduce the risk of hypersensitivity reactions, fluid retention, and other side effects such as nausea.

4. Warnings and Precautions:

• Myelosuppression: Docetaxel can cause significant bone marrow suppression, leading to neutropenia, anemia, and thrombocytopenia. Regular monitoring of blood counts is essential, especially during the first few cycles of treatment.
• Hypersensitivity reactions: Severe hypersensitivity reactions, including anaphylaxis, can occur. Premedication with corticosteroids and antihistamines is required to reduce this risk.
• Fluid Retention: Docetaxel may cause fluid retention, resulting in peripheral edema and weight gain. This can lead to serious complications such as pleural effusion, ascites, and other forms of fluid retention. Use with caution in patients with pre-existing heart conditions.
• Neurotoxicity: Peripheral neuropathy (numbness, tingling, and pain in the extremities) may occur, especially in patients who have received other neurotoxic agents or have pre-existing neuropathy.
• Hepatic Impairment: Docetaxel is metabolized in the liver; dose adjustments may be necessary in patients with liver dysfunction.
• Cardiac Events: Cardiotoxicity is rare, but docetaxel can cause arrhythmias and heart failure. Careful monitoring is required, especially in patients with existing heart conditions.
• Severe gastrointestinal effects: Nausea, vomiting, and diarrhea may occur, requiring the use of antiemetics and supportive care.

5. Contraindications:

• Known hypersensitivity to docetaxel or any component of the formulation.
• Severe neutropenia or active infection.
• Pregnancy (Category D) or breastfeeding, as docetaxel may harm the fetus or infant.

6. Side Effects:

• Common:
  • Myelosuppression (neutropenia, thrombocytopenia, anemia)
  • Nausea and vomiting
  • Fatigue
  • Hair loss (alopecia)
  • Diarrhea
  • Edema (fluid retention, peripheral edema)
  • Peripheral neuropathy (numbness, tingling)
  • Stomatitis (mouth sores)
• Serious:
  • Hypersensitivity reactions (anaphylaxis, rash, urticaria)
  • Severe infections (due to myelosuppression)
  • Severe fluid retention (pleural effusion, ascites, edema)
  • Severe mucositis
  • Hepatotoxicity (elevated liver enzymes, jaundice)

7. Drug Interactions:

• CYP3A4 Inhibitors: Docetaxel is metabolized by the CYP3A4 enzyme. Co-administration with CYP3A4 inhibitors (e.g., ketoconazole, ritonavir) may increase docetaxel levels and increase the risk of toxicity. Dose reduction may be necessary.
• CYP3A4 Inducers: Co-administration with CYP3A4 inducers (e.g., rifampin) may decrease docetaxel efficacy by lowering blood levels.
• Other Chemotherapy Agents: Docetaxel is frequently combined with other chemotherapy agents like cisplatin and cyclophosphamide. Increased toxicity, especially myelosuppression, should be monitored carefully in combination regimens.

8. Monitoring:

• Complete Blood Count (CBC): Frequent blood count monitoring is needed to detect myelosuppression (particularly neutropenia and thrombocytopenia).
• Liver Function Tests: Periodically check liver enzymes (AST, ALT) and bilirubin to assess for hepatic toxicity, particularly in patients with liver impairment.
• Fluid status: Monitor for signs of fluid retention, including weight gain, edema, and difficulty breathing (which may suggest pleural effusion or ascites).
• Neurological status: Monitor for signs of peripheral neuropathy, such as tingling or numbness in the extremities.

9. Pregnancy Category:

• Category D: Docetaxel can cause fetal harm and should not be used during pregnancy unless the potential benefit justifies the risk to the fetus. Effective contraception should be used during treatment and for a period of time after treatment.

10. Storage:

• Storage: Docetaxel injection (RTU) should be stored at room temperature (20°C to 25°C / 68°F to 77°F) and protected from light.
• Shelf Life: Ready-to-use docetaxel should be used within 2 hours of opening.