Docetaxel Anhydrous is the anhydrous form of docetaxel, a semisynthetic side-chain analog of paclitaxel with the antineoplastic property. Docetaxel binds specifically to the beta-tubulin subunit of microtubules and thereby antagonizes the disassembly of the microtubule proteins. This results in the persistence of aberrant microtubule structures and results in cell-cycle arrest and subsequent cell death.
Mechanism of Action of Docetaxel
Docetaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, docetaxel arrests their function by having the opposite effect; it hyper-stabilizes their structure. This destroys the cell’s ability to use its cytoskeleton in a flexible manner. Specifically, docetaxel binds to the β-subunit of tubulin. Tubulin is the “building block” of microtubules, and the binding of docetaxel locks these building blocks in place. The resulting microtubule/docetaxel complex does not have the ability to disassemble. This adversely affects cell function because the shortening and lengthening of microtubules (termed dynamic instability) is necessary for their function as a transportation highway for the cell. Chromosomes, for example, rely upon this property of microtubules during mitosis. Further research has indicated that docetaxel induces programmed cell death (apoptosis) in cancer cells by binding to an apoptosis stopping protein called Bcl-2 (B-cell leukemia 2) and thus arresting its function.
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Docetaxel, a semisynthetic taxane, has exhibited significant single-agent activity against prostatic tumors. In phase I/II studies, single-agent docetaxel and the combination of docetaxel plus estramustine were effective in inducing prostate-specific antigen reductions of > or = 50% in men with androgen-independent prostate cancer (AIPC). The underlying reason for docetaxel’s clinical activity against prostate cancer has been a focus of ongoing research. Docetaxel is believed to have a twofold mechanism of antineoplastic activity: (1) inhibition of microtubular depolymerization, and (2) attenuation of the effects of bcl-2 and bcl-xL gene expression. Taxane-induced microtubule stabilization arrests cells in the G(2)M phase of the cell cycle and induces bcl-2 phosphorylation, thereby promoting a cascade of events that ultimately leads to apoptotic cell death. In preclinical studies, docetaxel had a higher affinity for tubulin and was shown to be a more potent inducer of bcl-2 phosphorylation than paclitaxel. Laboratory evidence also supports the clinical evaluation of docetaxel-based combinations that include agents such as trastuzumab and/or estramustine. The pathways for docetaxel-induced apoptosis appear to differ in androgen-dependent and androgen-independent prostate cancer cells. Further elucidation of these differences will be instrumental in designing targeted regimens for the treatment of localized and advanced prostate cancer.
Indications of Docetaxel
- For the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. Also used as a single agent in the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy.
- It is also used in combination with prednisone, in the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer. Furthermore, docetaxel has uses in the treatment of gastric adenocarinoma and head and neck cancer.
- Non-Small Cell Lung Cancer
- Breast Cancer
- Gastric Cancer
- Head and Neck Cancer
- Prostate Cancer
- Esophageal Cancers
- Ewing’s Sarcoma
- Locally Advanced Breast Cancer
- Lung Cancer Small Cell Lung Cancer
- Metastatic Bladder Cancer
- Metastatic Breast Cancer
- Metastatic Hormone Refractory Prostate Cancer
- Metastatic Non-Small Cell Lung Cancer
- Node-Positive Breast Cancer
- Ovarian Cancer Metastatic
- Soft Tissue Sarcoma (STS)
- Advanced untreated gastric adenocarcinoma
- Locally advanced Squamous cell carcinoma of head and neck
- Locally advanced untreated nonsmall cell lung cancer
- Metastatic Squamous cell carcinoma of head and neck
- Refractory, locally advanced Nonsmall cell lung cancer
- Refractory, metastatic Nonsmall cell lung cancer
Therapeutic Uses
- Antineoplastic Agents; Tubulin Modulators
- Taxotere is indicated for the treatment of patients with locally advanced or metastatic breast cancer after failure of prior chemotherapy. Taxotere in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of patients with operable node-positive breast cancer.
- Taxotere as a single agent is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of prior platinum-based chemotherapy. Taxotere in combination with cisplatin is indicated for the treatment of patients with unresectable, locally advanced or metastatic non-small cell lung cancer who have not previously received chemotherapy for this condition.
- Taxotere in combination with prednisone is indicated for the treatment of patients with androgen independent (hormone refractory) metastatic prostate cancer. /Included in US product labeling/
- Taxotere in combination with cisplatin and fluorouracil is indicated for the treatment of patients with advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have not received prior chemotherapy for advanced disease.
- Taxotere in combination with cisplatin and fluorouracil is indicated for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).
- Docetaxel is used in combination with doxorubicin for the first-line treatment of metastatic breast cancer
- Docetaxel in combination with carboplatin is used an as alternative regimen for the first-line treatment of ovarian epithelial cancer.
Contra-Indications of Docetaxel
- Severe infection
- Anemia
- Decreased Blood Platelets
- Decreased Neutrophils a Type of White Blood Cell
- Peripheral pain, numbness, tingling, or weakness. সহজ বাংলা: স্নায়ুর ক্ষতি/সমস্যা।" data-rx-term="neuropathy" data-rx-definition="Neuropathy means nerve damage or irritation causing pain, numbness, tingling, or weakness. সহজ বাংলা: স্নায়ুর ক্ষতি/সমস্যা।">neuropathy
- Disorder of the Peripheral Nerves that Cause Movement
- Macular Swelling and Degeneration of the Eye
- Heart Compression caused by Excess Fluid in the Covering
- Failure of the Left Ventricle of the Heart
- Escape of Fluid into the Lungs
- Fluid in the Lungs
- Painful
- Red or Swollen Mouth
- Liver problems
- Visible Water Retention
- Fluid Retention in the Legs
- Feet
- Arms or Hands
- High Amount of jaundice. সহজ বাংলা: জন্ডিসে বাড়তে পারে এমন হলুদ রঞ্জক।" data-rx-term="bilirubin" data-rx-definition="Bilirubin is a yellow pigment that can build up in jaundice. সহজ বাংলা: জন্ডিসে বাড়তে পারে এমন হলুদ রঞ্জক।">Bilirubin in the Blood
- Diarrhea
- Ascites
- Abnormal liver function tests
- Pregnancy
- A mother who is producing milk and breastfeeding
- Severely Decreased Levels of Neutrophils in the Blood
- Lung Tissue Problems
- Allergies to Docetaxel & Paclitaxel/Docetaxel
Dosage of Docetaxel
Strengths: 10 mg/mL; 40 mg/mL; 20 mg/mL; 20 mg; 80 mg
Breast Cancer
- Single-agent – 60 to 100 mg/m2 IV over 1 hour every 3 weeks
- Adjuvant – 75 mg/m2 IV over 1 hour administered 1 hour after doxorubicin 50 mg/m2 IV and cyclophosphamide 500 mg/m2 IV every 3 weeks for 6 cycles; prophylactic G-CSF may be used to mitigate the risk of hematological toxicities
Non-Small Cell Lung Cancer
- As a single agent after failure of prior platinum-based chemotherapy – 75 mg/m2 IV over 1 hour every 3 weeks
- Chemotherapy-naive patients – 75 mg/m2 IV over 1 hour immediately followed by cisplatin 75 mg/m2 IV over 30 to 60 minutes; repeat every 3 weeks
Gastric Cancer
- 75 mg/m2 IV over 1 hour followed by cisplatin 75 mg/m2 IV over 1 to 3 hours (both on Day 1 only), followed by fluorouracil 750 mg/m2 daily given as a 24-hour continuous IV infusion for 5 days, starting at the end of the cisplatin infusion; repeat every 3 weeks
Head and Neck Cancer
Induction therapy of locally advanced inoperable SCCHN
- Day 1: 75 mg/m2 IV over 1 hour followed by cisplatin 75 mg/m2 IV over 1 hour, on Day 1, followed by fluorouracil 750 mg/m2 as a continuous IV infusion daily for 5 days
- Administer this regimen every 3 weeks for 4 cycles.
- Following chemotherapy, patients should receive radiotherapy.
Induction therapy for locally advanced (unresectable, low surgical cure, or organ preservation) SCCHN
- Day 1: 75 mg/m2 IV over 1 hour followed by cisplatin 100 mg/m2 administered as a 30-minute to 3-hour IV infusion, followed by fluorouracil 1000 mg/m2/day as a continuous IV infusion from Day 1 to Day
- Repeat therapy every 3 weeks for 3 cycles.
- Following chemotherapy, patients should receive radiotherapy.
Prostate Cancer
- 75 mg/m2 IV over 1 hour every 3 weeks; prednisone 5 mg orally 2 times a day is administered continuously
Side Effects of Docetaxel
More Common
- Congestion
- diarrhea
- dryness or soreness of the throat
- Burning, numbness, tingling, or pain in the arms, hands, legs, or feet
- swelling of the stomach, face, fingers, hands, feet, or lower legs
- unusual tiredness or weakness
- weight gain
- nausea
- skin rash or redness (mild)
- sores or ulcers on the lips or tongue or inside the mouth
- weakness in the arms, hands, legs, or feet
Less Common
- Black, tarry stools
- blood in the urine or stools
- cough or hoarseness (accompanied by fever or chills)
- difficult or labored breathing
- difficult or painful urination (accompanied by fever or chills)
- difficulty with swallowing
- dizziness
- fast heartbeat
- fever or chills
- hives or skin rash
- itching, puffiness, or swelling of the eyelids or around the eyes, face, lips, or tongue
- lower back or side pain (accompanied by fever or chills)
- noisy, rattling breathing
- pinpoint red spots on the skin
- red, scaly, swollen, or peeling areas of the skin (severe)
- tightness in the chest
- troubled breathing while at rest
- unusual bleeding or bruising
Drug Interactions of Docetaxel
Docetaxel may interact with following drugs, supplements & may change the efficacy of drugs
- other cancer medications (e.g., cisplatin, doxorubicin, teniposide, etoposide, vincristine)
- amiodarone
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- barbiturates (e.g., phenobarbital, secobarbital)
- boceprevir
- bosentan
- carbamazepine
- carvedilol
- clozapine
- conivaptan
- cyclosporine
- deferasirox
- desipramine
- dexamethasone
- diltiazem
- echinacea
- grapefruit juice
- HIV non-nucleoside reverse transcriptase inhibitors (NNRTIs; e.g., delaviridine, efavirenz, etravirine, nevirapine)
- HIV protease inhibitors (e.g., atazanavir, indinavir, ritonavir, saquinavir)
- leflunomide
- lomitapide
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- mefloquine
- natalizumab
- nefazodone
- norfloxacin
- phenytoin
- pimecrolimus
- primidone
- progesterone
- propranolol
- quinidine
- quinine
- rifabutin
- rifampin
- “statin” cholesterol medications (e.g., atorvastatin, pravastatin, simvastatin)
- tacrolimus
- tamoxifen
- telaprevir
- tyrosine kinase inhibitors (e.g., dasatinib, imatinib, nilotinib)
- vaccines
- verapamil
Pregnancy Category of
FDA Pregnancy Category – D
Pregnancy
There are no adequate studies of use of this medication by pregnant women. This medication should not be taken during pregnancy. If you become pregnant while taking this medication, contact your doctor immediately.
Lactation
It is not known if docetaxel passes into breast milk. Women should not breast-feed while using docetaxel. The safety and effectiveness of using this medication have not been established for children.
References
