paclitaxel (Taxol)
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Introduction
Indications
- ovarian cancer
- metastatic ovarian carcinoma after failure of 1st-line agent
- breast cancer
- non small cell lung carcinomas
- gastric cancer
- metastatic melanoma
- acute leukemia
- Kaposi's sarcoma[7]
- head & neck cancer
- esophageal cancer
- endometrial cancer
- bladder cancer
- cervical cancer
- testicular cancer
- pancreatic adenocarcinoma[7]
Dosage
- standard premedication
- 50 mg diphenhydramine
- 300 mg cimetidine
- 10-20 mg dexamethasone
- antiemetics
- depends upon nausea potential of combination chemotherapy
- prochlorperazine is sufficient if Taxol is used alone
- post chemotherapy dexamethasone 4 mg PO TID
- 135-175 mg/m2
- doses of 200-250 mg/m2 have been used
- radiosensitizer dose 30 mg/m2
- lower doses have been given weekly with better efficacy & less adverse effects
- paclitaxel is given prior to cisplatin when used in combination
- carboplatin is given prior to paclitaxel when used in combination
- administered in non PVC, with 0.22 micron filter
Injection: in polyethoxylated castor oil (Camophor EL) 50% & alcohol: 6 mg/mL (5 mL).
Abraxane: solvent-free, albumin-bound formulation
Pharmacokinetics
- high protein binding
- metabolized in the liver by cyt P450 3A4
- 1/2 life is triphasic, approximately 6 hours
elimination via liver
Adverse effects
- common (> 10%)
- myalgia
- abnormal liver function tests
- bone marrow suppression
- neutropenia
- onset 8 days
- nadir 11 days
- recovery 15-21 days
- thrombocytopenia
- less frequent & severe than neutropenia
- nadir 8-9 days
- more frequent & severe in patients with prior radiation
- neutropenia
- alopecia
- observed in nearly all patients
- occurs suddenly after 14-21 days
- reversible
- other[2][3]
- mild nausea
- mucositis
- allergic reactions
- bronchospasm
- peripheral neuropathy[3]
- progressive, predominantly sensory neuropathy
- dose-dependent
- muscle strength is generally preserved
- results from inhibition of microtubule formation in dorsal root ganglia
- arthralgias
- hypotension
- bradycardia
- heart failure (if given with doxorubicin)[3]
- hand & foot syndrome[3]
- frozen gloves & socks for 90 minutes after undergoingtreatment with paclitaxel may help control symptoms of neuropathy[9]
Drug interactions
- aminoglycosides given within 3-5 days can increased risk of ototoxicity
- cisplatin exacerbates myelosuppression
- ketoconazole may inhibit metabolism of Taxol
- any drug that inhibits cyt P450 3A4 may increase levels of paclitaxel
- any drug that induces cyt P450 3A4 may diminish levels of paclitaxel
Laboratory
Mechanism of action
- stabilizes microtubules & inhibits tubulin disassembly
- causes cell-cycle arrest in metaphase
More general terms
More specific terms
Additional terms
Component of
References
- ↑ Wahl et al Nature Medicine 2:72 1996
- ↑ 2.0 2.1 Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ 3.0 3.1 3.2 3.3 3.4 Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 17. American College of Physicians, Philadelphia 1998, 2012, 2015
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ Prescriber's Letter 13(2): 2006 Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220215&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 7.0 7.1 7.2 Deprecated Reference
- ↑ Perez EA, Suman VJ, Davidson NE et al Cardiac safety analysis of doxorubicin and cyclophosphamide followed by paclitaxel with or without trastuzumab in the North Central Cancer Treatment Group N9831 adjuvant breast cancer trial. J Clin Oncol. 2008 Mar 10;26(8):1231-8 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18250349
- ↑ 9.0 9.1 Bassett M Cryotherapy May Help Prevent Neuropathy in Cancer Patients. Less CIPN in patients wearing ice-cold gloves and socks after taxane therapy. MedPage Today. October 12, 2017 https://www.medpagetoday.com/HematologyOncology/Chemotherapy/68498
Hanai A, Ishiguro H, Sozu T et al Effects of Cryotherapy on Objective and Subjective Symptoms of Paclitaxel-Induced Neuropathy: Prospective Self-Controlled Trial. JNCI: J Natl Cancer Institute, 110(2) Feb 1 2018 Not indexed in PubMed https://academic.oup.com/jnci/article/4443215/Effects-of-Cryotherapy-on-Objective-and-Subjective