Brands, Medical Use, Clinical Data
Brands / Synonyms
7-epi-Paclitaxel; 7-epi-Taxol; 7-Epipaclitaxel; 7-Epitaxol; Abraxane; Epitaxol; LipoPac; Onxol; Paclitaxel; Paxceed; Paxene; Taxol; Taxol (TN); Taxol A
Used in the treatment of Kaposi's sarcoma and cancer of the lung, ovarian, and breast.
Paclitaxel is a taxoid antineoplastic agent indicated as first-line and subsequent therapy for the treatment of advanced carcinoma of the ovary, and other various cancers including breast cancer. Paclitaxel is a novel antimicrotubule agent that promotes the assembly of microtubules from tubulin dimers and stabilizes microtubules by preventing depolymerization. This stability results in the inhibition of the normal dynamic reorganization of the microtubule network that is essential for vital interphase and mitotic cellular functions. In addition, paclitaxel induces abnormal arrays or "bundles" of microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.
Mechanism of Action
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 mictotubules, 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.
Rat (ipr) LD50=32530 µg/kg. Symptoms of overdose include bone marrow suppression, peripheral neurotoxicity, and mucositis. Overdoses in pediatric patients may be associated with acute ethanol toxicity.
Biotrnasformation / Drug Metabolism
Hepatic. In vitro studies with human liver microsomes and tissue slices showed that paclitaxel was metabolized primarily to 6a-hydrox-ypaclitaxel by the cytochrome P450 isozyme CYP2C8; and to two minor metabolites, 3’-p-hydroxypaclitaxel and 6a, 3’-p-dihydroxypaclitaxel, by CYP3A4.
TAXOL is contraindicated in patients who have a history of hypersensitivity reactions to TAXOL or
other drugs formulated in Cremophor® EL (polyoxyethylated castor oil).
TAXOL should not be used in patients with solid tumors who have baseline neutrophil counts of <1500
cells/mm3 or in patients with AIDS-related Kaposi’s sarcoma with baseline neutrophil counts of
In a Phase I trial using escalating doses of TAXOL (110-200 mg/m2) and cisplatin (50 or 75
mg/m2) given as sequential infusions, myelosuppression was more profound when TAXOL was given after
cisplatin than with the alternate sequence (ie, TAXOL before cisplatin). Pharmacokinetic data from these patients
demonstrated a decrease in paclitaxel clearance of approximately 33% when TAXOL was administered following
The metabolism of TAXOL is catalyzed by cytochrome P450 isoen-zymes CYP2C8 and CYP3A4. In the absence of formal
clinical drug interaction studies, caution should be exercised when administering TAXOL concomitantly with known
substrates or inhibitors of the cytochrome P450 isoenzymes CYP2C8 and CYP3A4.
Potential interactions between TAXOL, a substrate of CYP3A4, and protease inhibitors (ritonavir, saquinavir,
indinavir, and nelfinavir), which are substrates and/or inhibitors of CYP3A4, have not been evaluated in clinical
Reports in the literature suggest that plasma levels of doxorubicin (and its active metabolite doxorubicinol) may
be increased when paclitaxel and doxorubicin are used in combination.
Hematology: TAXOL therapy should not be administered to patients with baseline neutrophil counts of
less than 1,500 cells/mm3. In order to monitor the occurrence of myelotoxicity, it is recommended that
frequent peripheral blood cell counts be performed on all patients receiving TAXOL. Patients should not be re-treated
with subsequent cycles of TAXOL until neutrophils recover to a level >1500 cells/mm3 and platelets
recover to a level >100,000 cells/mm3. In the case of severe neutropenia (<500 cells/mm3
for seven days or more) during a course of TAXOL therapy, a 20% reduction in dose for subsequent courses of therapy
For patients with advanced HIV disease and poor-risk AIDS-related Kaposi’s sarcoma, TAXOL, at the
recommended dose for this disease, can be initiated and repeated if the neutrophil count is at least 1000
Hypersensitivity Reactions: Patients with a history of severe hypersensitivity reactions to products
containing Cremophor® EL (eg, cyclosporin for injection concentrate and teniposide for injection
concentrate) should not be treated with TAXOL. In order to avoid the occurrence of severe hypersensitivity reactions,
all patients treated with TAXOL should be premedicated with corticosteroids (such as dexamethasone), diphen-hydramine
and H2 antagonists (such as cimetidine or ranitidine). Minor symptoms such as flushing, skin reactions, dyspnea,
hypotension, or tachycardia do not require interruption of therapy. However, severe reactions, such as hypotension
requiring treatment, dyspnea requiring bronchodilators, angioedema, or generalized urticaria require immediate
discontinuation of TAXOL and aggressive symptomatic therapy. Patients who have developed severe hypersensitivity
reactions should not be rechallenged with TAXOL.
Cardiovascular: Hypotension, bradycardia, and hypertension have been observed during administration
of TAXOL, but generally do not require treatment. Occasionally TAXOL infusions must be interrupted or discontinued
because of initial or recurrent hypertension. Frequent vital sign monitoring, particularly during the first hour of
TAXOL infusion, is recommended. Continuous cardiac monitoring is not required except for patients with serious
Nervous System: Although the occurrence of peripheral neuropathy is frequent, the development of
severe symptomatology is unusual and requires a dose reduction of 20% for all subsequentcourses of TAXOL.
TAXOL contains dehydrated alcohol USP, 396 mg/mL; consideration should be given to possible CNS and other effects
Hepatic: There is limited evidence that the myelotoxicity of TAXOL may be exacerbated in patients
with serum total bilirubin >2 times ULN. Extreme caution should be exercised when administering TAXOL to such
patients, with dose reduction as recommended in DOSAGE AND ADMINISTRATION, Table
InjectionSite Reaction: Injection site reactions, including reactions secondary to extravasation,
were usually mild and consisted of erythema, tenderness, skin discoloration, or swelling at the injection site. These
reactions have been observed more frequently with the 24-hour infusion than with the 3-hour infusion. Recurrence of
skin reactions at a site of previous extravasation following administration of TAXOL at a different site, ie,
"recall", has been reported rarely.
Rare reports of more severe events such as phlebitis, cellulitis, induration, skin exfoliation, necrosis, and
fibrosis have been received as part of the continuing surveillance of TAXOL safety. In some cases the onset of the
injection site reaction either occurred during a prolonged infusion or was delayed by a week to ten days.
A specific treatment for extravasation reactions is unknown at this time. Given the possibility of extravasation,
it is advisable to closely monitor the infusion site for possible infiltration during drug administration.