It is a semisynthetic taxane prepared with a precursor extracted from european yew plants. Docetaxel is slightly more water soluble than paclitaxel and a more potent antimicrotubule agent in vitro, reduction in peripheral neuropathies as compared to paclitaxel.
Mechanism of Action
- Binds to free tubulin and promotes assembly of tubulin into stable microtubules while simultaneously inhibiting their disassembly.
- Stabilization of microtubules results in loss of normal function of microtubules with resultant inhibition of mitosis.
- Antiangiogenic effects
- In vitro analyses demonstrate docetaxel to be 100-fold more potent than paclitaxel in bcl-2 phosphorylation and apoptotic cell death.
Mechanism of Resistance
- Alterations in tubulin with decreased affinity for drug.
- Multidrug-resistant (MDR-1) phenotype with increased expression of P170 glycoprotein. Results in enhanced drug efflux with decreased intracellular accumulation of drug.
- Cross-resistant to other products, including vinca alkaloids, anthracyclines.
- Extensive binding (>90%) to plasma and cellular proteins.
- Extensively metabolized by the hepatic P450 microsomal system.
- About 75% of drug is excreted via fecal elimination.
- Renal clearance is less than 10% . Terminal half-lives ranging from 11.1 to 18.5 hours have been reported.
- Use with caution in patients with abnormal liver function. Patients with abnormal liver function are at significantly higher risk for toxicity, including treatment-related mortality.
Doses or Concentrations Available
- Docetaxel injection concentrate: 20 mg( 1 ml) , 80 mg(4 ml) , 120 mg(6 ml) .Stored below 25 degrees
- Solvent for Docetaxel injection concentrate: 5 ml vial for 20 mg, 6 ml for 80 mg, 9 ml for 120 mg.
- We have to bring the concentrate at room temperature by allowing it to stand at room temperature for 5 minutes after taking from refrigerator. Then reconstitute with solvent. Inject this premix into 250 ml NS or 5% Dextrose. Mix thoroughly, solution should be clear and there should be no precipitation.
FDA-approved for the treatment of metastatic or recurrent breast cancer after failure of prior anthracycline based chemotherapy .
Docetaxel single agent 60-100 mg/m2 every 3 weeks.
AT ( Doxorubicin 50 mg/m2+ Docetaxel 75 mg/m2 everv 3 weeks ) ;
Docetaxel ( 75 mg/m2 on day 1) + Capecitabine 950 mg/2 BD for 14 days every 3 weeks
For adjuvant treatment of patients with node positive breast cancer.
FEC→ Docetaxel ( 100 mg/m2 every 3 weeks)
TAC ( Docetaxel+ Doxoru + Cyclophos)
TC ( Docetaxel + Cyclophos)
TCH ( Docetaxel + Carboplatin + Trastuzumab )
Metastatic or locally advanced gastric adenocarcinoma – Adjuvant CT :DCF ( 75 mg/m2 every 3 weeks)
Head and neck cancer – FDA-approved for use in combination with cisplatin and 5-fluorouracil for induction treatment of patients with inoperable, locally advanced disease. 75 mg/m2 every 3 weeks.
Prostate cancer—FDA-approved in combination with prednisone for androgen-independent (hormone-refractory) metastatic prostate cancer.
Non–small cell lung cancer—Locally advanced or metastatic disease after failure of prior platinum-based chemotherapy. FDA-approved 75 mg/m 2 IV every 3 weeks or 35–40 mg/m 2 IV weekly for 3 weeks with 1 week rest.
Non–small cell lung cancer: non resectable 75 mg/m 2 IV every 3 weeks in combination with cisplatin in patients who have not received prior chemotherapy.
Recurrent ovarian cancer : platinum sensitive ( Docetaxel + carboplatin ) ; platinum resistant ( Docetaxel single agent).
- Neutropenia is the main toxicity of docetaxel.
- Grade 4 neutropenia with ANC < 500/mm3 occurs 100 % with 100 mg/m2 and 75-80% with 60-75 mg/m2).
- When docetaxel is administered on an every 3-week schedule, the onset of neutropenia is usually noted on day 8 with complete resolution by days 15 to 21.
- Neutropenia is significantly less when low doses are administered weekly.
- Closely monitor CBCs, and docetaxel therapy should not be given to patients with neutrophil counts of <1,500 cells/mm 3 .
- Thrombocytopenia and anemia are also observed
- The solvent used for Docetaxel is poly-oxy-ethylated surfactant, polysorbate-80 which causes alteration of membrane fluidity, increased capillary permeability
- Fluid retention is cumulative and Incidence increases with total doses >400 mg/m 2 . Occurs in about 50% of patients.
- Prophylactic Dexamethasone 8 mg BD for 3-5 days beginning one day prior to docetaxel infusion. Aggressive and early treatment with diuretics has been successfully used to manage fluid retention.
- This syndrome resolves slowly once docetaxel therapy is stopped, with complete resolution occurring several months after treatment in patients who experience severe toxicity.
- Hypersensitivity reactions with generalized skin rash, erythema, hypotension,dyspnea, and/or bronchospasm.
- The most popular prophylactic regimen for prevention of hypersensitivity reaction and fluid retention syndrome is dexamethasone 8 mg orally twice daily for 3 or 5 days starting 1 or 2 days before docetaxel, with or without H1– and H2-receptor antagonists given 30 minutes before docetaxel. Overall incidence decreased to less than 3%.
- Maculopapular skin rash and dry, itchy skin. Most commonly affect forearms and hands. Brown discoloration of fingernails may occur. Observed in up to 50% of patients usually within 1 week after therapy.
- Other cutaneous effects include palmar-plantar erythrodysesthesia.
- Alopecia occurs in up to 80% of patients.
- Mucositis and/or diarrhea seen in 40% of patients. Mild to moderate nausea and vomiting, usually of brief duration.
- Peripheral neuropathy is less commonly observed with docetaxel than with paclitaxel.
- Generalized fatigue and asthenia are common, occurring in 60%–70% of patients. Arthralgias and myalgias also observed.
- Reversible elevations in serum transaminases, alkaline phosphatase, and bilirubin.
- Phlebitis and/or swelling can be seen at the injection site