What is Docitaxel?

What is Docetaxel?

Docetaxel is an antineoplastic chemotherapy agent belonging to the taxoid family that works by disrupting microtubular networks essential for cell division, leading to cell death. 1

Drug Classification and Mechanism

• Docetaxel is a semisynthetic taxane derivative prepared from a precursor extracted from the renewable needle biomass of yew plants 1
• The drug binds to free tubulin and promotes the assembly of tubulin into stable microtubules while simultaneously inhibiting their disassembly, which results in inhibition of mitosis and cell death 1
• It produces microtubule bundles without normal function, leading to cell cycle arrest at G2/M phase and apoptosis 2

Chemical Properties

• The chemical formula is C43H53NO14 with a molecular weight of 807.88 1
• Docetaxel is highly lipophilic and practically insoluble in water 1
• It is approximately 94-97% protein bound in plasma, mainly to α1-acid glycoprotein, albumin, and lipoproteins 1

FDA-Approved Indications

Docetaxel is FDA-approved for multiple solid tumor malignancies:

• Metastatic castration-resistant prostate cancer (mCRPC) as a category 1 preferred option, typically dosed at 75 mg/m² every 3 weeks with prednisone 3
• Metastatic breast cancer after failure of prior chemotherapy, with demonstrated superiority over other agents 3, 4
• Non-small cell lung cancer (NSCLC) both as first-line and second-line therapy 3, 5
• Advanced gastric cancer as part of combination regimens, particularly the DCF regimen (docetaxel/cisplatin/5-fluorouracil) 3, 6

Standard Dosing Regimens

The most commonly used dosing schedules are:

• Every 3 weeks: 75-100 mg/m² IV over 1 hour (standard regimen) 3
• Every 2 weeks: 50 mg/m² (alternative with improved tolerability; febrile neutropenia rate 4% vs 14% with every-3-week dosing) 3
• Weekly: 30 mg/m² for 5 out of every 6 weeks (less neutropenia but slightly less effective) 7

Pharmacokinetics

• Docetaxel follows a three-compartment pharmacokinetic model with a terminal elimination half-life of approximately 12 hours (range 92-135 hours with extended sampling) 1, 2
• Mean total body clearance is approximately 18-22 L/h/m² 1, 2
• The drug is metabolized primarily by the CYP3A4 isoenzyme in the liver 1, 2
• Approximately 75% is excreted in feces and only 6% in urine within 7 days 1

Major Toxicities and Safety Considerations

The dose-limiting toxicity is myelosuppression, particularly neutropenia:

• Grade 3-4 neutropenia occurs in 65-86% of patients depending on dose and regimen 3
• Febrile neutropenia rates range from 4-14% depending on schedule 3
• Patients should receive therapeutic G-CSF as soon as possible after overdose discovery 1

Other significant adverse effects include:

• Fluid retention syndrome (common with cumulative dosing) 5
• Peripheral neuropathy 1
• Mucositis 3
• Fatigue and cutaneous reactions 1

Critical Contraindications and Warnings

• Patients with severe hepatic impairment should not receive docetaxel 1
• Patients with combined abnormalities of transaminase and alkaline phosphatase should not be treated with docetaxel 1
• In patients with mild to moderate liver impairment (AST/ALT >1.5× ULN with alkaline phosphatase >2.5× ULN), total body clearance is lowered by 27%, resulting in 38% increased systemic exposure 1

Drug Interactions

• Caution is required with CYP3A4 inhibitors (erythromycin, ketoconazole, cyclosporin) as they may increase docetaxel exposure 2
• Conversely, CYP3A4 inducers (anticonvulsants) may require increased docetaxel doses 2
• Dexamethasone does not affect protein binding of docetaxel 1

Clinical Evidence for Survival Benefit

In metastatic castration-resistant prostate cancer:

• The TAX 327 trial demonstrated that every-3-week docetaxel resulted in higher median overall survival than mitoxantrone (18.9 vs 16.5 months; P=0.009) 3
• Approximately 45-50% of patients achieve a 50% decrease in PSA, typically assessed after 12 weeks of treatment 7

In metastatic castration-sensitive prostate cancer:

• The CHAARTED trial showed docetaxel plus ADT improved overall survival compared to ADT alone (57.6 vs 47.2 months; HR 0.72; P=0.002), particularly in high-volume disease 3

Formulation Details

• Docetaxel Injection is supplied as a ready-to-use solution at 20 mg/mL concentration 1
• Available in single-dose vials containing 20 mg (1 mL), 80 mg (4 mL), or 160 mg (8 mL) 1
• The solution contains polysorbate 80 and 50% v/v dehydrated alcohol, which should be considered in patients with hepatic impairment 1
• No prior dilution with diluent is required; the injection is ready to add directly to infusion solution 1