Paclitaxel is a chemotherapy drug that belongs to the class of mitotic inhibitors. It works by promoting microtubule polymerization and stabilization, which prevents microtubule depolymerization, thereby inhibiting mitosis and cell division. This leads to cell cycle arrest, particularly in the G2/M phase, causing the cell to undergo apoptosis (programmed cell death).

1. Indications:

Paclitaxel is used in the treatment of various cancers, including:

1. Ovarian cancer: As a first-line treatment for advanced ovarian cancer, in combination with other agents such as cisplatin.
2. Breast cancer: For adjuvant therapy (early-stage) and metastatic breast cancer.
3. Non-small cell lung cancer (NSCLC): For advanced or metastatic disease, often in combination with cisplatin.
4. Kaposi’s sarcoma: In patients with acquired immunodeficiency syndrome (AIDS).
5. Other indications: Occasionally used for other malignancies like esophageal cancer, cervical cancer, and head and neck cancers.

2. Dosage and Administration:

Dosing Regimens:

• Ovarian cancer:
  • Initial dose: 175 mg/m² IV over 3 hours every 3 weeks (combined with cisplatin).
• Breast cancer:
  • Dosing varies based on the chemotherapy regimen, but typically 175 mg/m² every 3 weeks.
• Non-small cell lung cancer:
  • Paclitaxel is typically dosed at 135-175 mg/m² over 3 hours every 3 weeks, combined with cisplatin.

3. Administration:

• Intravenous (IV) administration only—Paclitaxel should be administered through a central line or large peripheral vein to reduce the risk of severe extravasation reactions.
• Premedication: Patients are usually premedicated with corticosteroids (e.g., dexamethasone), antihistamines (e.g., diphenhydramine), and H2 blockers (e.g., ranitidine) to prevent hypersensitivity reactions.
• Infusion rate: Administer paclitaxel at a rate of 1-2 mg/min for the first 15 minutes and increase the rate if tolerated.

4. Warnings and Precautions:

• Hypersensitivity reactions: Severe reactions, including anaphylaxis, can occur. Premedication is recommended to reduce the risk.
• Bone marrow suppression: Paclitaxel can cause severe myelosuppression, including neutropenia, thrombocytopenia, and anemia. Regular blood counts are necessary.
• Peripheral neuropathy: Dose-limiting peripheral neuropathy can occur, particularly with prolonged use or higher doses.
• Cardiotoxicity: Bradycardia, heart block, and other arrhythmias may occur.
• Hepatic impairment: Paclitaxel should be used with caution in patients with liver dysfunction, as it is metabolized by the liver. Dose adjustments may be necessary.
• Extravasation: Extravasation of paclitaxel can cause severe tissue damage. Proper infusion techniques and monitoring are essential.

5. Contraindications:

• Known hypersensitivity to paclitaxel or any component of the formulation.
• Pregnant women (paclitaxel can cause fetal harm).
• Severe neutropenia or active infections (due to bone marrow suppression).

6. Side Effects:

• Common:
  • Myelosuppression (neutropenia, thrombocytopenia, anemia)
  • Nausea and vomiting
  • Hair loss (alopecia)
  • Peripheral neuropathy
  • Fatigue
  • Diarrhea
• Serious:
  • Hypersensitivity reactions (e.g., anaphylaxis, rash, urticaria)
  • Severe infections (due to neutropenia)
  • Cardiotoxicity (arrhythmias, bradycardia)
  • Hepatotoxicity (liver dysfunction)
  • Severe mucositis

7. Drug Interactions:

• CYP450 Inhibitors/Inducers: Since paclitaxel is metabolized by the liver enzymes CYP3A4 and CYP2C8, inhibitors (e.g., ketoconazole, ritonavir) and inducers (e.g., rifampin) may affect paclitaxel levels. Dose adjustments may be needed.
• Other Chemotherapy Agents: Paclitaxel can interact with other cytotoxic agents, leading to increased toxicity or altered therapeutic effects.

8. Monitoring:

• Complete blood counts (CBC): To monitor for myelosuppression, especially neutropenia and thrombocytopenia.
• Liver function tests: Given the hepatic metabolism of paclitaxel, liver function tests should be monitored periodically.
• Electrocardiogram (ECG): To detect any arrhythmias, especially in patients with existing cardiovascular concerns.
• Neurological evaluation: Monitor for symptoms of peripheral neuropathy.

9. Pregnancy Category:

• Category D: Paclitaxel can cause fetal harm and should be avoided during pregnancy unless the potential benefit justifies the risk to the fetus.

10. Storage:

• Paclitaxel injection should be stored at room temperature (20°C to 25°C / 68°F to 77°F) and protected from light.
• Avoid freezing.