Docetor

Approved Indications:

• Breast cancer:
• Adjuvant treatment of node-positive breast cancer following surgery and chemotherapy.
• Treatment of metastatic breast cancer.
• Non-small cell lung cancer (NSCLC):
• First-line treatment in combination with cisplatin for locally advanced or metastatic disease.
• Second-line treatment following failure of prior platinum-based chemotherapy.
• Prostate cancer:
• Hormone-refractory metastatic prostate cancer, typically in combination with prednisone.
• Gastric cancer:
• Advanced gastric adenocarcinoma, including gastroesophageal junction adenocarcinoma, in combination with cisplatin and fluorouracil.
• Head and neck cancer:
• Locally advanced squamous cell carcinoma of the head and neck, in combination with cisplatin and fluorouracil.

Off-label Uses:

• Occasionally used in other solid tumors where taxanes are indicated.

Route: Intravenous infusion only.

General Dosing Guidelines (Adults):

• Breast cancer (Adjuvant):
• 75 mg/m² IV infusion every 3 weeks for 4 cycles, often following 4 cycles of doxorubicin and cyclophosphamide.
• Metastatic breast cancer:
• 60–100 mg/m² IV every 3 weeks.
• Non-small cell lung cancer:
• 75–100 mg/m² IV every 3 weeks in combination with cisplatin.
• Prostate cancer:
• 75 mg/m² IV every 3 weeks with oral prednisone 5 mg twice daily.
• Gastric and head & neck cancer:
• 75 mg/m² IV every 3 weeks in combination regimens.

Infusion Time:

• Administer over 1 hour; infusion time may be extended to reduce hypersensitivity risk.

Premedication:

• Corticosteroids (e.g., dexamethasone 8 mg twice daily for 3 days starting 1 day prior) to reduce risk of hypersensitivity and fluid retention.

Pediatrics:

• Safety and efficacy not established.

Elderly:

• Use with caution; monitor for toxicity.

Renal/Hepatic Impairment:

• Avoid use in severe hepatic impairment (bilirubin >1.5 × ULN or AST/ALT >2.5 × ULN).
• No specific dose adjustment for renal impairment, but use caution.

Docetaxel is a semisynthetic taxane that promotes and stabilizes microtubule assembly by binding to β-tubulin subunits. This stabilization inhibits microtubule depolymerization, thereby blocking the dynamic reorganization of the microtubule network essential for mitotic and interphase cellular functions. The result is inhibition of mitotic cell division, leading to apoptosis of rapidly dividing cancer cells.

• Absorption: Administered IV; complete bioavailability.
• Distribution: Extensive tissue distribution; highly bound (~95%) to plasma proteins.
• Metabolism: Metabolized primarily by hepatic CYP3A4 enzymes to inactive metabolites.
• Half-life: Terminal elimination half-life approx. 11 hours (range 11–18 hours).
• Elimination: Mainly eliminated via feces (approximately 75%); <5% excreted unchanged in urine.

• Pregnancy: FDA Category D
• Documented teratogenicity and embryotoxicity in animal studies.
• Contraindicated during pregnancy unless potential benefits outweigh risks.
• Lactation:
• Unknown if excreted in human milk.
• Breastfeeding not recommended during treatment due to potential toxicity.

• Primary Class: Antineoplastic agent
• Subclass: Taxane antimitotic agent

• Known hypersensitivity to docetaxel, other taxanes, or polysorbate 80 (excipient)
• Severe neutropenia or thrombocytopenia prior to treatment
• Severe hepatic impairment
• Pregnancy and lactation unless benefits outweigh risks

• Myelosuppression: Severe neutropenia with risk of infections; monitor CBC regularly.
• Hypersensitivity reactions: Can be severe or fatal; premedication with corticosteroids is mandatory.
• Fluid retention: May cause edema, pleural effusion, and ascites; monitor and manage accordingly.
• Hepatic impairment: Dose modification or avoidance recommended.
• Neuropathy: Peripheral sensory neuropathy can occur; monitor symptoms.
• Pulmonary toxicity: Rare but serious interstitial pneumonitis reported.
• Cardiac effects: Monitor for arrhythmias and heart failure in predisposed patients.

Common:

• Hematologic: Neutropenia, anemia, thrombocytopenia
• Gastrointestinal: Nausea, vomiting, diarrhea, mucositis
• Alopecia
• Fatigue
• Fluid retention/edema
• Neuropathy (paresthesia, neuropathic pain)
• Nail changes

Serious / Rare:

• Febrile neutropenia
• Severe hypersensitivity reactions (anaphylaxis)
• Hepatic toxicity
• Interstitial lung disease
• Cardiac arrhythmias

• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin):
• Increase docetaxel plasma concentration → increased toxicity risk.
• CYP3A4 inducers (e.g., rifampin, phenytoin):
• Decrease docetaxel plasma concentration → reduced efficacy.
• Other myelosuppressive agents:
• Additive bone marrow suppression.
• Live vaccines:
• Avoid during therapy due to immunosuppression.

• Recent oncology guidelines emphasize the importance of corticosteroid premedication to reduce hypersensitivity and fluid retention.
• Dose adjustments recommended in hepatic impairment.
• Increasing evidence supports combination therapies incorporating docetaxel for advanced solid tumors.
• Monitoring for neuropathy and early intervention has been highlighted in supportive care protocols.

• Store at 2°C to 8°C (36°F to 46°F) (refrigerated)
• Protect from light
• Do not freeze
• Use reconstituted solutions promptly; if storage is necessary, use within 8 hours at 2–25°C and protect from light.