paclitaxel

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paclitaxel

 [pak″lĭ-tak´sel]
an antineoplastic agent that acts by promoting and stabilizing the polymerization of microtubules, isolated from the Pacific yew tree (Taxus brevifolia); used in the treatment of advanced ovarian or breast carcinoma, non–small cell lung carcinoma, and AIDS-related Kaposi's sarcoma. Administered intravenously.

paclitaxel

Apo-Paclitaxel (CA), Paxene (UK)

Pharmacologic class: Antimicrotubule agent

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Box Warning

• Give injection under supervision of physician experienced in use of cancer chemotherapy, in facility with adequate diagnostic and treatment resources.

• Anaphylaxis and severe hypersensitivity reactions may occur despite premedication. All patients should be pretreated with corticosteroids, diphenhydramine, and histamine2 antagonists. Don't give drug to patients who've had previous severe reactions.

• Don't administer drug to patients with solid tumors whose baseline neutrophil counts are below 1,500 cells/mm3 or to patients with AIDS-related Kaposi's sarcoma whose baseline neutrophil counts are below 1,000 cells/mm3. To monitor for bone marrow suppression, obtain frequent peripheral blood cell counts on all patients.

• Albumin form of drug may substantially affect drug's functional properties. Don't substitute for or use with other paclitaxel forms.

Action

Stabilizes cellular microtubules to prevent depolymerization. This action inhibits microtubule network (essential for vital interphase and mitotic cellular functions) and induces abnormal microtubule arrays or bundles throughout cell cycle and during mitosis.

Availability

Concentrate for injection: 30 mg/5-ml vial, 100 mg/16.7-ml vial, 300 mg/50-ml vial

Indications and dosages

Advanced ovarian cancer

Adults: As first-line therapy, 175 mg/m2 I.V. over 3 hours q 3 weeks, or 135 mg/m2 I.V. over 24 hours q 3 weeks, followed by cisplatin. After failure of first-line therapy, 135 mg/m2 I.V. or 175 mg/m2 I.V. over 3 hours q 3 weeks.

Breast cancer after failure of combination chemotherapy

Adults: As adjuvant treatment for node-positive breast cancer, 175 mg/m2 I.V. over 3 hours q 3 weeks for four courses given sequentially with doxorubicin combination chemotherapy. After chemotherapy failure for metastatic disease or relapse within 6 months of adjuvant therapy, 175 mg/m2 I.V. over 3 hours q 3 weeks.

Non-small-cell lung cancer

Adults: 135 mg/m2 I.V. over 24 hours q 3 weeks, followed by cisplatin

AIDS-related Kaposi's sarcoma

Adults: 135 mg/m2 I.V. over 3 hours q 3 weeks, or 100 mg/m2 I.V. over 3 hours q 2 weeks

Dosage adjustment

• Advanced human immunodeficiency virus infection (when used for Kaposi's sarcoma)

Off-label uses

• Advanced head and neck cancer
• Small-cell lung cancer
• Upper GI tract adenocarcinoma
• Non-Hodgkin's lymphoma
• Pancreatic cancer
• Polycystic kidney disease

Contraindications

• Hypersensitivity to drug or castor oil
• Solid tumors when baseline neutrophil count is below 1,500 cells/mm3
• AIDS-related Kaposi's sarcoma when baseline neutrophil count is below 1,000 cells/mm3

Precautions

Use cautiously in:
• severe hepatic impairment, active infection, decreased bone marrow reserve, chronic debilitating illness
• patients with childbearing potential
• breastfeeding patients (not recommended)
• children (safety not established).

Administration

Follow facility protocol for handling chemotherapeutic drugs and preparing solutions.
• Dilute in dextrose 5% in water, normal saline solution, or dextrose 5% in lactated Ringer's solution per manufacturer's guidelines.
• Inspect solution for particles. Administer through polyethylene-lined administration set attached to 0.22-micron in-line filter.
• To prevent severe hypersensitivity reaction, premedicate with dexamethasone 20 mg 12 and 6 hours before infusion, as prescribed. Also give diphenhydramine 50 mg I.V., plus either cimetidine 300 mg or ranitidine 50 mg I.V. 30 to 60 minutes before paclitaxel.

Keep epinephrine available. If severe hypersensitivity reaction occurs, stop infusion immediately and give epinephrine, I.V. fluids, and additional antihistamine and corticosteroid doses, as indicated and prescribed.

Adverse reactions

CNS: peripheral neuropathy

CV: hypotension, hypertension, syncope, abnormal ECG, bradycardia, venous thrombosis

GI: nausea, vomiting, diarrhea, stomatitis, mucositis

Hematologic: anemia, leukopenia, neutropenia, bleeding, thrombocytopenia

Musculoskeletal: joint pain, myalgia

Skin: alopecia, radiation reactions

Other: infection, injection site reaction, hypersensitivity reactions including anaphylaxis

Interactions

Drug-drug. Carbamazepine, phenobarbital: decreased paclitaxel blood level and efficacy

Cisplatin: increased bone marrow depression (when paclitaxel dose follows cisplatin dose)

Cyclosporine, diazepam, doxorubicin, felodipine, ketoconazole, midazolam: inhibited paclitaxel metabolism and greater risk of toxicity

Doxorubicin: increased doxorubicin blood level and toxicity

Live-virus vaccines: decreased antibody response to vaccine, increased risk of adverse reactions

Other antineoplastics: increased risk of bone marrow depression

Drug-diagnostic tests.Liver function tests: abnormal results

Triglycerides: increased levels

Patient monitoring

Watch closely for hypersensitivity reaction.
• Monitor heart rate and blood pressure.
• Assess infusion site for local effects and extravasation, especially during prolonged infusion.

Monitor CBC, including platelet count. If neutropenia develops, monitor patient for infection; if thrombocytopenia develops, watch for signs and symptoms of bleeding.
• If patient has preexisting cardiac conduction abnormality, maintain continuous cardiac monitoring.

Patient teaching

• Instruct neutropenic patient to minimize infection risk by avoiding crowds, plants, and fresh fruits and vegetables.
• Tell thrombocytopenic patient to avoid activities that can cause injury. Advise him to use soft toothbrush and electric razor.

Advise patient to promptly report signs and symptoms of infection, bleeding, or peripheral neuropathy (such as numbness and tingling of feet and hands).
• Tell patient to promptly report pain or burning at injection site.
• Explain that temporary hair loss may occur.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

pac·li·tax·el

(pak'lĭ-taks'ĕl),
Antitumor agent that promotes microtubule assembly by preventing depolymerization; currently used in salvage therapy for metastatic carcinoma of ovary.

paclitaxel

/pac·li·tax·el/ (pak″lĭ-tak´sel) an antineoplastic that promotes and stabilizes polymerization of microtubules, isolated from the Pacific yew tree (Taxus brevifolia); used in the treatment of advanced ovarian or breast carcinoma, non, and AIDS-related Kaposi's sarcoma.

paclitaxel

(păk′lĭ-tăk′səl)
n.
An anticancer drug that was first derived from the bark of the Pacific yew tree and is used in the treatment of ovarian and breast cancer that has not responded to prior therapy.

paclitaxel

an anticancer drug derived from the bark of the rare, slow-growing Pacific yew tree. It is used in the treatment of ovarian cancer. Paclitaxel prevents cancer cells from dividing; it arrests cell division by attaching to microtubules that regulate the formation of spindles necessary for cell division. The anticancer effect of paclitaxel was discovered by the National Cancer Institute in 1963 during a routine investigation of thousands of plant compounds. It takes about 60 pounds of yew bark to produce enough paclitaxel to treat a single patient for several weeks. Semisynthetic and synthetic methods of production have reduced, but not eliminated, the use of yew bark.

paclitaxel

Paxene®, Taxol Oncology An antimitotic anticancer taxane used for KS, breast and ovarian CAs. See Breast CA, Ovarian CA.

pac·li·tax·el

(pak'li-taks'ĕl)
Antitumor agent that promotes microtubule assembly by preventing depolymerization; used in salvage therapy for ovarian metastatic carcinoma.

paclitaxel

A TAXANE anticancer drug used mainly to treat ovarian cancer and widespread breast cancer. A brand name is Taxol.

Paclitaxel

A drug derived from the common yew tree (Taxus baccata) that is the mainstay of chemotherapy for ovarian cancer.
Mentioned in: Ovarian Cancer

pac·li·tax·el

(pak'li-taks'ĕl)
Antitumor agent that promotes microtubule assembly by preventing depolymerization; currently used in salvage therapy for metastatic carcinoma of ovary and other cancers.

paclitaxel (pak´litak´səl),

n brand name: Taxol;
drug class: antineoplastic;
action: obtained from Western Yew tree, unique action inhibits microtubule network reorganization essential for cell division;
use: metastatic ovarian cancer.
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