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Paclitaxel Indications is a compound extracted from the Pacific yew tree Taxus brevifolia with antineoplastic activity. Paclitaxel binds to tubulin and inhibits the disassembly of microtubules, thereby resulting in the inhibition of cell division. This agent also induces apoptosis by binding to and blocking the function of the apoptosis inhibitor protein Bcl-2 (B-cell Leukemia 2). (NCI04)
Paclitaxel Celibate is the celibate ester form of paclitaxel, a compound extracted from the Pacific yew tree Taxus brevifolia with antineoplastic activity. Paclitaxel binds to and stabilizes tubulin thereby inhibiting the disassembly of microtubules, resulting in the inhibition of cell division. This agent also induces apoptosis by binding to and blocking the function of the apoptosis inhibitor protein B-cell Leukemia 2 (BCL2).
Mechanism of Action of Paclitaxel
Paclitaxel interferes with the normal function of microtubule growth. Whereas drugs like colchicine cause the depolymerization of microtubules in vivo, paclitaxel 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, paclitaxel binds to the β subunit of tubulin. Tubulin is the “building block” of microtubules, and the binding of paclitaxel locks these building blocks in place. The resulting microtubule/paclitaxel 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 paclitaxel 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.
or
Evidence suggests that paclitaxel also may induce cell death by triggering apoptosis. In addition, paclitaxel and docetaxel enhance the effects of ionizing radiation, possibly by blocking cells in the G2 phase, the phase of the cell cycle in which cells are most radiosensitive.
Paclitaxel Indications
Antineoplastic Agents, Phytogenic; Radiation-Sensitizing Agents
- Used in the treatment of Kaposi’s sarcoma and cancer of the lung, ovarian, and breast. Abraxane is specifically indicated for the treatment of metastatic breast cancer and locally advanced or metastatic non-small cell lung cancer.
- Paclitaxel is an antineoplastic agent which acts by an inhibitor of cellular mitosis and which currently plays a central role in the therapy of ovarian, breast, and lung cancer. Therapy with paclitaxel has been associated with a low rate of serum enzyme elevations but has not been clearly linked to cases of clinically apparent acute liver injury.
- Paclitaxel is approved to be used alone or with other drugs to treats – AIDS-related Kaposi sarcoma.
- Non-small cell lung cancer.
- Ovarian cancer.
- Paclitaxel is also being studied in the treatment of other types of cancer. Paclitaxel is also available in a different form called paclitaxel albumin-stabilized nanoparticle formulation. For more information, see the Drug Information Summary for Paclitaxel Albumin-stabilized Nanoparticle Formulation.
- Squamous cell head and neck cancer, small-cell lung cancer, bladder cancer, endometrial cancer, esophageal cancer, prostate cancer, gastric cancer, testicular cancer, and germ cell tumors. Paclitaxel has also been used for refractory leukemia and recurrent Wilms tumor in children.
- Breast Cancer
- Breast Cancer, Adjuvant
- Breast Cancer, Metastatic
- Kaposi’s Sarcoma
- Non-Small Cell Lung Cancer
- Wilms’ Tumor
- Treatment of advanced AIDS-related Kaposi’s sarcoma (KS), metastatic carcinoma of the breast (MBC), advanced carcinoma of the ovary (AOC), metastatic carcinoma of the ovary (MOC), non-small cell lung carcinoma (NSCLC).
- Apealea in combination with carboplatin is indicated for the treatment of adult patients with the first relapse of platinum-sensitive epithelial ovarian cancer, primary peritoneal cancer, and fallopian tube cancer
- Abraxane monotherapy is indicated for the treatment of metastatic breast cancer in adult patients who have failed first-line treatment for metastatic disease and for whom standard, anthracycline containing therapy is not indicated.
- Abraxane in combination with gemcitabine is indicated for the first-line treatment of adult patients with metastatic adenocarcinoma of the pancreas.
- Abraxane in combination with carboplatin is indicated for the first-line treatment of non-small cell lung cancer in adult patients who are not candidates for potentially curative surgery and/or radiation therapy.
Contraindications of Paclitaxel
- Severe infection
- Decreased function of bone marrow
- Anemia
- Decreased Blood Platelets
- 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
- Heart attack
- Slow Heartbeat
- Abnormal heart rhythm
- Abnormally low blood pressure
- Liver problems
- 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
- Abnormal liver function tests
- Pregnancy
- A mother who is producing milk and breastfeeding
- Severely Decreased Levels of Neutrophils in the Blood
Allergies
- Paclitaxel
- Paclitaxel/Docetaxel
Dosage of Paclitaxel
Strengths: 6 mg/mL
Breast Cancer
After the failure of initial chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy
- 175 mg/m2 IV over 3 hours every 3 weeks
Ovarian Cancer
For previously untreated patients with cancer of the ovary
- 175 mg/m2 IV over 3 hours every 3 weeks followed by cisplatin
Or
- 135 mg/m2 IV over 24 hours every 3 weeks followed by cisplatin
For patients previously treated for cancer of the ovary
- 175 mg/m2 IV over 3 hours every 3 weeks
Or
- 135 mg/m2 IV over 3 hours every 3 weeks
Non-Small Cell Lung Cancer
- 135 mg/m2 IV over 24 hours followed by cisplatin every 3 weeks
Kaposi’s Sarcoma
For patients with AIDS-Related Kaposi’s Sarcoma
- 135 mg/m2 IV over 3 hours every 3 weeks
Or
- 100 mg/m2 IV over 3 hours every 2 weeks
Side Effects of Paclitaxel
More Common
- Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।" data-rx-term="inflammation" data-rx-definition="Inflammation is the body’s response to injury, infection, or irritation, often causing pain, swelling, heat, or redness. সহজ বাংলা: শরীরের প্রদাহ; ব্যথা, ফোলা বা লালভাব হতে পারে।">inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, ulceration, or warmth at the injection site
- cracked lips
- diarrhea
- difficulty with swallowing
- hair loss
- nausea or vomiting
- numbness, burning or tingling in the hands or feet
- pain in the joints or muscles, especially in the arms or legs
Common
- Black or tarry stools
- blurred vision
- burning, numbness, tingling, or painful sensations
- confusion
- cough or hoarseness with fever or chills
- dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
- feeling of warmth
- fever or chills
- lower back or side pain
- painful or difficult urination
- pale skin
- redness of the face, neck, arms, and occasionally, upper chest
Rare
- blurred vision or other visual changes
- cough or hoarseness with fever or chills
- fever or chills
- fast or irregular heartbeat, or lightheadedness occurring during your treatment
- pain or redness at the site of the injection
- severe weakness or tiredness
- signs of clotting problems (e.g., unusual nosebleeds, bruising, blood in urine, coughing blood, bleeding gums, cuts that don’t stop bleeding)
- signs of infection (symptoms may include fever or chills, severe diarrhea, shortness of breath, prolonged dizziness, headache, stiff neck, weight loss, or listlessness)
- signs of liver problems (e.g., nausea, vomiting, diarrhea, loss of appetite, weight loss, yellowing of the skin or whites of the eyes, dark urine, pale stools)
- shortness of breath or wheezing
- skin rash or itching or hives
- symptoms of a urinary tract infection (e.g. pain when urinating, urinating more often than usual, low back or flank pain)
Drug Interactions of Paclitaxel
Paclitaxel may interact with following drugs, supplements & may change the efficacy of drugs
- atorvastatin
- “azole” antifungals (e.g., itraconazole, ketoconazole, voriconazole)
- barbiturates (e.g., phenobarbital, secobarbital)
- BCG vaccine
- calcium channel blockers (e.g., amlodipine, diltiazem, nifedipine, verapamil)
- carbamazepine
- carvedilol
- celecoxib
- cimetidine
- clopidogrel
- clozapine
- corticosteroids (e.g., budesonide, dexamethasone, hydrocortisone, fluticasone, prednisone)
- cyclosporine
- denosumab
- desipramine
- dexamethasone
- estrogens
- gemfibrozil
- grapefruit juice
- haloperidol
- infliximab
- irbesartan
- losartan
- macrolide antibiotics (e.g., clarithromycin, erythromycin)
- metronidazole
- mifepristone
- montelukast
- modafinil
- mycophenolate
- natalizumab
- norfloxacin
- phenobarbital
- phenytoin
- prazosin
- progesterone
- rabeprazole
- rituximab
- St. John’s Wort
- saxagliptin
- tacrolimus
- tamoxifen
- testosterone
- tetracycline
- thiazolidinediones (e.g., pioglitazone, rosiglitazone)
- tocilizumab
- trastuzumab
- trimethoprim
- warfarin
Pregnancy Category
AU TGA Pregnancy Category: D
US FDA Pregnancy Category: D
Pregnancy
There are no adequate studies of the use of this medication by pregnant women, however, paclitaxel may cause severe harm to a developing baby if it is used by the mother during pregnancy. This medication should not be used during pregnancy. If you become pregnant while taking this medication, contact your doctor immediately.
Lactation
It is not known if paclitaxel passes into breast milk. If you are a breastfeeding mother and are taking this medication, it may affect your baby. Talk to your doctor about whether you should continue breastfeeding. The safety and effectiveness of using this medication have not been established for children.
References
