Updated: February 5, 2008
SYNONYM(S): NSC-1259731
COMMON TRADE NAMES: generic available, ONXOL® (USA), TAXOL®
CLASSIFICATION: antimicrotubule agent, cytotoxic2
Special pediatric considerations are noted when applicable, otherwise adult provisions apply.
MECHANISM OF ACTION: Paclitaxel is an antimicrotubule agent that promotes the assembly and stabilization of microtubules from tubulin dimers.3 Late G2 mitotic phase is inhibited and thus cell replication is inhibited.4 Paclitaxel also can distort mitotic spindles resulting in chromosomal damage.4
PHARMACOKINETICS:
|
Interpatient variability |
no information found |
|
Oral Absorption |
not absorbed orally |
|
Distribution |
biphasic; initial rapid distribution to the peripheral compartment, then a slow efflux of paclitaxel from the peripheral compartment; widely distributed into body fluids and tissues; affected by dose and duration of infusion4 |
|
cross blood brain barrier? |
no |
|
volume of distribution |
198-688 L/m2; varies with dose and infusion time |
|
plasma protein binding |
89-98%4 |
|
Metabolism |
hepatic via the cytochrome P450 isozymes CYP2C8/9 and CYP3A4 |
|
active metabolite(s) |
primarily 6α-hydroxypaclitaxel |
|
inactive metabolite(s) |
yes |
|
Excretion |
elimination follows non-linear (saturable) pharmacokinetics5,6; high concentrations found in bile |
|
urine |
14% (1.3-12.6% as unchanged drug)4 |
|
feces |
71% (5% as unchanged drug) |
|
terminal half life |
3.0-52.7 h; varies with dose and infusion time
(e.g., 3 h infusion of 175 mg/m2: 9.9 h) |
|
clearance |
11.6-24.0 L/h/m2; varies with dose and infusion time
(e.g., 3 h infusion of 175 mg/m2: 12.4 L/h/m2) |
|
Gender |
no information found |
|
Elderly |
clearance7 |
11.4-16.2 L/h/m2 |
|
Children |
terminal half life4 |
4.6-17 h |
|
Ethnicity |
no information found |
Adapted from standard reference8 unless specified otherwise.
USES:
|
Primary uses: |
Other uses: |
|
* Breast cancer |
Bladder cancer4 |
|
Cervical cancer9 |
Head and neck cancer4 |
|
Endometrial cancer10 |
Leukemias4 |
|
* Kaposi’s Sarcoma |
Malignant melanoma4 |
|
* Lung cancer |
|
|
* Ovarian cancer |
|
*Health Canada approved indication
SPECIAL PRECAUTIONS:
Hypersensitivity reactions (HSR)8: Paclitaxel infusions may be associated with acute hypersensitivity reactions; incidence is significantly reduced by premedication and increased infusion times. For more information refer to the hypersensitivity reaction paragraph following the side effect table.
Carcinogenicity: Not yet studied.11
Elderly patients are at an increased risk for developing toxicities (e.g., arthralgia, myalgia, neutropenia, neuropathy).4
Mutagenicity8: Paclitaxel was not mutagenic in the Ames test. Paclitaxel was clastogenic in the mammalian in vitro and in vivo chromosome tests.
Fertility: The effects of paclitaxel on fertility have not been established. Women of childbearing potential should be counselled to avoid pregnancy.9
Pregnancy: FDA Pregnancy Category D. There is positive evidence of human fetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Breastfeeding is not recommended due to the potential secretion into breast milk.11
SIDE EFFECTS:
The table includes adverse events that presented during drug treatment but may not necessarily have a causal relationship with the drug. Because clinical trials are conducted under very specific conditions, the adverse event rates observed may not reflect the rates observed in clinical practice. Adverse events are generally included if they were reported in more than 1% of patients in the product monograph or pivotal trials, and/or determined to be clinically important.10,12 When placebo-controlled trials are available, adverse events are included if the incidence is > 5% higher in the treatment group, and the frequencies provided are compared to the incidence in the placebo-controlled arms of the trials.
ORGAN SITE |
SIDE EFFECT |
ONSET |
|
Clinically important side effects are in bold, italics
I = immediate (onset in hours to days); E = early (days to weeks);
D = delayed (weeks to months); L = late (months to years) |
|
allergy/immunology |
hypersensitivity reactions (severe 1%) |
I |
|
|
|
|
blood/bone marrow/
febrile neutropenia |
anemia (62%, severe 6%) |
|
E |
|
|
|
neutropenia (severe 6-21%)4; nadir 8-11 days, recovery 15-21 days |
I |
|
|
|
|
thrombocytopenia (6%) |
I |
|
|
|
|
cardiovascular (arrhythmia) |
arrhythmias9 (1%) (e.g., asymptomatic ventricular tachycardia, atrial fibrillation, supraventricular tachycardia, junctional tachycardia) |
I |
|
|
|
|
bradycardia (25%); during infusion, transient4 |
I |
|
|
|
|
cardiovascular (general) |
electrocardiogram abnormalities (23%) |
I |
|
|
|
|
edema (21%) |
|
E |
|
|
|
hypertension (1%) |
I |
|
|
|
|
hypotension (24%); during infusion, transient |
I |
|
|
|
|
myocardial infarction (rare) |
|
|
D |
|
|
constitutional symptoms |
|
|
|
|
|
|
dermatology/skin |
extravasation hazard13: irritant |
|
alopecia (87%)4,14; usually complete, generally occurs 14-21 days after administration of paclitaxel with a sudden onset, often occurring in a single day9 |
|
E |
|
|
|
flushing (28%)4 |
I |
|
|
|
|
nail and skin changes (2%)12; mild, transient |
|
E |
|
|
|
radiation recall reaction (rare)14 |
|
E |
|
|
|
rash (12%)4 |
I |
|
|
|
|
gastrointestinal |
emetogenic potential15: low |
|
anorexia (25%) |
|
E |
|
|
|
constipation (18%) |
|
E |
|
|
|
diarrhea (38%) |
I |
|
|
|
|
intestinal obstruction (4%)12 |
|
E |
|
|
|
mucositis (31%); more common with 24 h infusion |
|
E |
|
|
|
nausea (52%)14; mild to moderate |
I |
|
|
|
|
stomatitis (15%)4; most common at doses >390 mg/m2 |
|
E |
|
|
|
taste perversion9 |
|
E |
|
|
|
vomiting (5-6%); mild to moderate4 |
I |
|
|
|
|
hepatic |
hepatic necrosis and hepatic encephalopathy (rare) |
|
|
D |
|
|
infection |
febrile neutropenia (12%) |
I |
|
|
|
|
neurology |
ataxia (<1%)4 |
|
E |
|
|
|
encephalopathy (rare) |
|
E |
|
|
|
ethanol intoxication4 |
I |
|
|
|
|
seizures (rare) |
|
E |
|
|
|
myopathy (25-50%)4 |
|
E |
|
|
|
peripheral neuropathy (64%, severe 4%) |
|
E |
|
|
|
metabolic/laboratory |
mild increase in liver enzymes (18%) |
I |
|
|
|
|
ocular/visual |
optic nerve and/or visual disturbances (rare) |
|
E |
|
|
|
pain |
arthralgia/myalgia (54%, severe 12%) |
I |
E |
|
|
|
pulmonary |
interstitial pneumonia, lung fibrosis (rare) |
|
|
D |
|
|
vascular |
pulmonary embolism (rare) |
I |
|
|
|
|
phlebitis (2%)4 |
I |
|
|
|
Adapted from standard reference8 unless specified otherwise.
Hypersensitivity reactions (HSR) are common with paclitaxel and appear to be due to a nonimmunologically-mediated release of histamine and other vasoactive substances.4 The exact cause is not known but may result from either the Cremophor EL in the paclitaxel injection or from the paclitaxel itself.9 HSR most often occur in the first hour of an infusion (75% occur within the first 10 minutes).4 The frequency and severity of these reactions are not affected by the dose or schedule of paclitaxel administration.3 Delayed onset of urticarial rash, 7-10 days following completion of a course of treatment, has been seen in some Kaposi’s sarcoma patients.9
Incidence of HSR are significantly reduced by premedication. Corticosteroids (e.g., dexamethasone), histamine H1-antagonists (e.g., diphenhydramine) and H2-antagonists (e.g., ranitidine) should be administered prior to paclitaxel administration to minimize the potential for anaphylaxis. The following is one suggested regimen for adults16-34:
- 45 minutes before paclitaxel, dexamethasone 20 mg IV
- 30 minutes before paclitaxel, diphenhydramine 50 mg IV and ranitidine 50 mg IV.
A more protracted premedication scheme, which may be more effective, particularly where a patient has exhibited HSR would be: 12 hours and 6 hours before paclitaxel, dexamethasone 20 mg po and then following the above premedication regime.10 In the event of a treatment delay (e.g., admixture is unavailable), additional doses are required. In premedicated patients, symptoms of HSR are reported in as many as 41%, although severe HSR occur in less than 2% of patients.3
The occurrence of HSR does not preclude rechallenge with paclitaxel.35 If there is a hypersensitivity reaction, the patient may be rechallenged after further premedication and with close monitoring.35 Prolonging the infusion to > 6 hours may decrease the incidence of hypersensitivity reactions4; 24, 96 and 120 hour infusions have been studied and show decreased HSR with increased infusion times.35
Treatment for hypersensitivity reactions, including general management, and management of hypotension, dyspnea and bronchospasm can be found in the BC Cancer Agency Protocol Summary of Hypersensitivity Reactions to Chemotherapeutic Agents (SCDRUGRX).36 See below for general management.
General Management36: It is recommended that patients are assessed by a physician if having a reaction requiring the administration of medications or as patient condition warrants.
|
Moderate
e.g., moderate rash, flushing, pruritus, mild dyspnea, chest discomfort, abdominal discomfort, lower back pain, mild hypotension |
- Stop infusion.
- Give diphenhydramine 25-50 mg IV and/or hydrocortisone sodium succinate 100 mg per physician orders.
- After recovery of symptoms, resume infusion at a rate per protocol. If no direction in protocol consider resuming at 25% of previous rate for at least 5 minutes, 50% for at least 5 minutes, 75% for at least 5 minutes and then full rate if no reaction.
- Depending on severity of reaction, may increase to full rate at physician’s discretion.
- Premedication for all future cycles (see Prophylaxis section in SCDRUGRX). Initiate infusion at slower rate (consider 50% of full rate) per physician orders.
|
|
Severe (potentially life threatening)
i.e., to be used if reaction escalates (e.g., one or more of respiratory distress requiring treatment, angioedema, hypotension requiring therapy) |
- Stop infusion and do not restart.
- Give diphenhydramine 50 mg IV push and/or hydrocortisone sodium succinate 100 mg IV push per physician orders.
- Oxygen if needed for dyspnea (see SCDRUGRX).
- Normal saline if needed for hypotension (see SCDRUGRX).
- Epinephrine or bronchodilators if indicated (see SCDRUGRX).
- Either permanently discontinue the drug or attempt to retreat on another occasion after premedication (see SCDRUGRX) and using slower infusion rate.
- Initiate Emergency Response System appropriate for facility if patient condition warrant.
|
IF there is a true anaphylactic reaction with paclitaxel despite premedication and a slow initial infusion rate the patient should not have a further rechallenge.10,35
Very rarely, fatal reactions have occurred in patients despite pre-treatment.11 Docetaxel has been successfully substituted in some patients who experienced severe HSR with paclitaxel;37-39 however, cross-sensitivity has also been reported.40
Arthralgia/myalgia is dose and schedule dependent; worse with higher doses and shorter infusions.41 The symptoms are usually transient, occur within two or three days after paclitaxel administration, and resolve after a few days.8 If arthralgia/myalgia from paclitaxel is grade 2 (moderate) or higher and is not relieved by adequate doses of NSAIDS or acetaminophen with codeine (e.g., TYLENOL #3®), a suggested symptomatic treatment includes16-23,25-32,34:
- gabapentin 300 mg po on day prior to paclitaxel, 300 mg po bid on treatment day and then 300 mg po tid x 7-10 days
- prednisone 10 mg po bid x 5 days starting 24 hours post-paclitaxel42
In non-curative protocols, if arthralgia/myalgia persists, subsequent paclitaxel dose reduction may be considered.20-23,26-29,34 In curative settings, there is no data on the efficacy of a reduced dose, so it is not advised unless toxicity is severe and precludes continuing paclitaxel without a dose reduction.35
Peripheral neuropathy is usually sensory in nature. Paclitaxel-induced neurotoxicity often appears as mild paresthesia characterized by numbness and tingling in a stocking-and-glove distribution.9 Perioral numbness may also occur, and many patients experience burning pain particularly in the feet.9 Onset may be rapid, occurring within a few days of an infusion.9 Frequency and severity are related to cumulative doses; toxicity may be dose-limiting.9 Sensory manifestations usually improve or resolve several months after discontinuing paclitaxel.9 Pre-existing neuropathies resulting from prior therapies are not a contraindication for treatment with paclitaxel; however, the incidence of paclitaxel-related neuropathy appears to be increased in this population of patients.3
Bradycardia and hypotension during paclitaxel administration is usually asymptomatic and generally does not require treatment.3 In some cases, paclitaxel administration may have to be interrupted or discontinued.3 Although the manufacturer recommends frequent monitoring of vital signs, particularly during the first hour of administration,3 this is not the standard of practice at the BC Cancer Agency.43 Based on nursing experience with paclitaxel administration, and consultation with medical oncology and pharmacy, the BC Cancer Agency has found that clinical observation of patients by nurses for early signs of a reaction is more valuable than taking vital signs every15 minutes.43 For more information refer to the hypersensitivity reaction paragraph below. Severe cardiac conduction abnormalities have rarely occurred during paclitaxel therapy.11 If patients develop significant conduction abnormalities during administration, appropriate treatment should be administered and continuous electrocardiographic monitoring should be performed during subsequent infusions.11
Ethanol is contained in the paclitaxel formulation at a concentration of 396 mg/mL. Consideration should be given to possible CNS effects including impaired ability to drive and operate machinery.3,8 CNS toxicity has been reported in pediatric patients receiving high doses of paclitaxel (350-420 mg/m2 as a 3 hour infusion). This toxicity may have resulted from the ethanol contained in the formulation.4
INTERACTIONS:
AGENT |
EFFECT |
MECHANISM |
MANAGEMENT |
|
doxorubicin4 |
increased doxorubicin efficacy and toxicity |
decreased clearance of doxorubicin |
monitor for increased cardiotoxicity (e.g., congestive heart failure) or consider using docetaxel instead of paclitaxel (docetaxel does not appear to share this same interaction potential)44 |
|
epirubicin45-51 |
toxicity of both agents may be increased when given concurrently, regardless of which drug is given first; lower neutrophil and platelet nadirs, and slower neutrophil recovery, have been observed |
increased levels of epirubicin metabolites, decreased paclitaxel clearance |
separate administration by 24 hours if possible |
|
gemcitabine52 |
delayed, moderate, possible; increased gemcitabine efficacy and toxicity |
unknown |
monitor for gemcitabine toxicity during coadministration |
|
platinum derivatives3
(e.g., carboplatin, cisplatin) |
increased paclitaxel toxicity; paradoxical decreased platelet toxicity from carboplatin10 |
decreased clearance of paclitaxel |
paclitaxel should be given first when administering as sequential infusions with either of these drugs |
|
trastuzumab53 |
may increase efficacy of paclitaxel |
unknown |
preferred method is to give trastuzumab first when administering as sequential infusions |
|
warfarin52 |
delayed, moderate suspected; the anticoagulant effect of warfarin may be increased |
decreased warfarin metabolism |
monitor coagulation parameters during coadministration or consider use of LMWH during course of chemotherapy10 |
Paclitaxel is a major CYP2C8/9 substrate, therefore drugs that are CYP2C8/9 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifampin and secobarbital) may decrease the levels/effects of paclitaxel.4 Likewise, drugs that are CYP2C8/9 inhibitors (e.g., fluconazole, gemfibrozil, ketoconazole, NSAIDS and sulfonamides) may increase the levels/effects of paclitaxel.4
Paclitaxel is a major CYP3A4 substrate, therefore drugs that are CYP3A4 inducers (e.g., aminoglutethimide, carbamazepine, nafcillin, phenobarbital and phenytoin) may decrease the levels/effects of paclitaxel.4 Herbs that are CYP3A4 inducers (e.g., St John’s Wort) may also decrease the levels/effects of paclitaxel. Likewise, drugs that are CYP3A4 inhibitors (e.g., azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, propofol, protease inhibitors, quinidine and verapamil) may increase the levels/effects of paclitaxel.4
Paclitaxel is also a weak CYP3A4 inducer.4
SUPPLY AND STORAGE:
Injection: Biolyse Pharma supplies paclitaxel as a 6 mg/mL preservative-free solution in single-dose vials of 5 mL, 16.7 mL and 50 mL.11 Non-medicinal ingredients: dehydrated ethanol 49.7% and Cremophor EL (polyethoxyethylated castor oil).11 Refrigeration is recommended for long term storage.11 The potency of paclitaxel is not affected when transported or stored for up to two months at room temperature.11 Protect vials from light (keep intact vials in their container until use).11 Discard unused portion within 8 hours after puncture.11
Bristol-Myers Squibb supplies paclitaxel as a 6 mg/mL preservative-free solution in multidose vials of 5 mL, 16.7 mL and 50 mL.3 Non-medicinal ingredients: dehydrated ethanol 49.7% and Cremophor EL (polyethoxylated castor oil) 527 mg.3 Store vials at room temperature and protect from light (keep intact vials in their container until use).54 Both the 5 mL vial and the 16.7 mL vial are stable for 48 hours at room temperature after puncture.3,55 The 50 mL vial is stable for 24 hours at room temperature after puncture.3
SOLUTION PREPARATION AND COMPATIBILITY:
For basic information on solution preparation and compatibility, see Chemotherapy Chart in Appendix.
Additional information: Non-polyvinyl (non-PVC) equipment (e.g., polyethylene) is used to minimize leaching. The surfactant,56 Cremophor EL (polyoxyethylated castor oil), leaches the plasticizer, diethylhexyl phthalate (DEHP), from polyvinyl chloride (PVC) bags and administration sets. Actual hazardous exposure levels to DEHP are not known57,58; however, it is hepatotoxic and exposure should be minimized.59 Use of a plastic syringe to measure a dose is acceptable but drug-syringe contact time should be minimized.
Bacterial challenge56: Paclitaxel (Bristol) 0.7 mg/mL diluted in NS did not exhibit an antimicrobial effect on the growth of three of four organisms inoculated into the solution. Microbiological growth should be considered when assigning expiration periods.
Compatibility: The following are compatible with paclitaxel via Y-site injection56: acyclovir, amikacin, aminophylline, ampicillin, bleomycin, butorphanol, calcium, carboplatin, cefepime, cefotetan, ceftazidime, ceftriaxone, cimetidine, cisplatin, cladribine, cyclophosphamide, cytarabine, dacarbazine, dexamethasone, diphenhydramine, doxorubicin, droperidol, etoposide, etoposide phosphate, famotidine, floxuridine, fluconazole, fluorouracil, furosemide, ganciclovir, gatifloxacin, gemcitabine, gentamicin, granisetron, haloperidol, heparin, hydrocortisone, hydromorphone, ifosfamide, linezolid, lorazepam, magnesium, mannitol, meperidine, mesna, methotrexate, metoclopramide, morphine, nalbuphine, ondansetron, pentostatin, potassium, prochlorperazine, propofol, ranitidine, sodium bicarbonate, thiotepa, topotecan, certain TPN formulations, vancomycin, vinblastine, vincristine, zidovudine.
The following are compatible with paclitaxel in the same infusion solution at certain concentrations and diluents56: carboplatin, cisplatin, doxorubicin.
Incompatibility: The following are incompatible with paclitaxel via Y-site injection56: amphotericin B, amphotericin B cholesteryl sulphate complex, chlorpromazine, doxorubicin liposomal, hydroxyzine, methylprednisolone, mitoxantrone.
Paclitaxel is incompatible in the same infusion solution at certain concentrations and diluents with cisplatin.56
PARENTERAL ADMINISTRATION:
|
BCCA administration guideline noted in bold, italics |
|
Subcutaneous |
not recommended |
|
Intramuscular |
not recommended |
|
Direct intravenous |
not recommended |
|
Intermittent infusion |
in appropriate volume of NS or D5W over 1-3 h (range 1-24 h)
- dilute in non-PVC bags
- dilute to final concentration of 0.3-1.2 mg/mL
- premedication required to prevent hypersensitivity reactions
- administer through non-PVC tubing and a 0.22 micron (non-PVC) in-line filter equipment
|
|
Continuous infusion |
as for intermittent infusion except given over 24 h |
|
Intraperitoneal |
has been used60 |
|
Intrapleural |
no information found |
|
Intrathecal |
no information found |
|
Intra-arterial |
no information found |
|
Intravesical |
no information found |
DOSAGE GUIDELINES:
Refer to protocol by which patient is being treated. Numerous dosing schedules exist and depend on disease, response and concomitant therapy. Guidelines for dosing also include consideration of absolute neutrophil count (ANC). Dosage may be reduced, delayed or discontinued in patients with bone marrow depression due to cytotoxic/radiation therapy or with other toxicities.
Adults:
|
|
|
BCCA usual dose noted in bold, italics |
|
|
|
|
Cycle Length: |
|
|
Intravenous: |
|
|
|
|
1 week4: |
50-80 mg/m2 over 1-3 hours on day 1 |
|
|
2 weeks17:
|
when given as a dose-dense regimen with filgrastim (G-CSF) support:
175 mg/m2 IV over 3 hours on day 1
(total dose per cycle 175 mg/m2)
|
|
|
3 weeks16,18-23,27,31,33,34: |
135-175 mg/m2 IV over 3 hours on day 1
(total dose per cycle 135-175 mg/m2)
|
|
|
3 weeks4: |
135 mg/m2 IV over 24 hours on day 1 |
|
|
4 weeks25: |
110 mg/m2 IV over 1 hour for one dose on days 1 and 8 and 15
(total dose per cycle 330 mg/m2)
|
|
|
4 weeks26,28-30: |
135-175 mg/m2 IV over 3 hours on day 1
(total dose per cycle 135-175 mg/m2)
|
|
|
|
|
|
Suggested premedication regimen16-34: |
any: |
45 minutes before: dexamethasone 20 mg IV
30 minutes before: diphenhydramine 50 mg IV; ranitidine 50 mg IV
In the event of a treatment delay (e.g., admixture is unavailable), additional doses are required.11 |
|
|
|
|
|
Concurrent radiation: |
generally not administered concurrently due to additive toxicity |
|
|
|
|
|
Dosage in myelosuppression: |
modify according to protocol by which patient is being treated; if no guidelines available, refer to Appendix 6 "Dosage Modification for Myelosuppression" |
|
|
|
|
|
Dosage in renal failure4: |
no adjustment required |
|
|
|
Dosage in hepatic failure4,61: |
Suggested guidelines for first course; subsequent courses should be based on individual tolerance |
|
paclitaxel 24 h infusion: |
|
ALT |
bilirubin |
dose |
|
<2 X ULN |
and |
<26 µmol/L |
135 mg/m2 |
|
2 to <10 X ULN |
and |
<26 µmol/L |
100 mg/m2 |
|
<10 x ULN |
and |
27-128 µmol/L |
50 mg/m2 |
|
>10 x ULN |
or |
>128 µmol/L |
not recommended |
|
paclitaxel 3 h infusion: |
|
ALT |
bilirubin |
dose |
|
<10 X ULN |
and |
<1.25 x ULN |
175 mg/m2 |
|
<10 X ULN |
and |
1.26-2.0 x ULN |
135 mg/m2 |
|
|
<10 X ULN |
and |
2.01-5.0 x ULN |
90 mg/m2 |
|
|
>10 x ULN |
or |
>5.0 x ULN |
not recommended |
|
|
|
Dosage in dialysis4: |
no significant removal by hemodialysis |
|
|
|
|
|
|
|
|
|
|
|
Children:
|
|
|
|
|
Cycle Length: |
|
Intravenous62-65: |
|
|
|
3 weeks: |
350 mg/m2 |
|
|
|
|
|
Suggested premedication regimen66: |
any: |
12 and 6 hours before: dexamethasone 0.15 mg/kg (up to 20 mg) po
OR 30 minutes before: 0.15 mg/kg (up to 20 mg) IV
30-60 minutes before: diphenhydramine 1 mg/kg (up to 50 mg) IV; ranitidine 1 mg/kg (up to 50 mg) IV
In the event of a treatment delay (e.g., admixture is not available), additional doses are required. |
References:
1. Dorr RT, Von-Hoff DD. Cancer chemotherapy handbook. 2nd ed. Norwalk, Connecticut: Appleton & Lange; 1994. p. 761-7.
2. National Institute for Occupational Safety and Health (NIOSH). Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Healthcare Settings. Cincinnati, OH; 25 March 2004.
3. Bristol-Myers Squibb Canada Pharmaceutical Group. Taxol product monograph. Montreal, Canada; 2002.
4. Paclitaxel: Drug Information. In: Rose BD, editor. UpToDate. Wellesley, MA,: UpToDate; 2006.
5. Panday VRN, Huizing MT, Willemse PHB, et al. Hepatic metabolism of paclitaxel and its impact in patients with altered hepatic function. Seminars in Oncology 1997;24(4 SUPPL. 11).
6. Venook AP, Egorin MJ, Rosner GL, et al. Phase I and pharmacokinetic trial of paclitaxel in patients with hepatic dysfunction: Cancer and Leukemia Group B 9264. Journal of Clinical Oncology 16(5):1811-9, 1998 May 1998.
7. Smorenburg CH, Ten Tije AJ, Verweij J, et al. Altered clearance of unbound paclitaxel in elderly patients with metastatic breast cancer. European Journal of Cancer 2003;39(2):196-202.
8. Bristol-Myers Squibb Pharmaceutical Group, Divison of Bristol-Myers Canada Inc. Taxol product monograph. Montreal Canada; 2006.
9. McEvoy GK, editor. AHFS 2005 Drug Information. Bethesda, Maryland: American Society of Health-System Pharmacists, Inc.; 2005. p. 1124-34.
10. Ken Swenerton. Personal communication. Gynecological Medical Oncologist, BC Cancer Agency Vancouver Centre 2005.
11. Biolyse Pharma. Paclitaxel product monograph. St. Catharines, Ontario; 2002.
12. Caroline Lohrisch, MD. Personal communication. Medical Oncologist, BC Cancer Agency Vancouver Centre 2005.
13. B.C. Cancer Agency Provincial Systemic Therapy Program. Provincial Systemic Therapy Program Policy III-20: Prevention and management of extravasation of chemotherapy. Vancouver, British Columbia: BC Cancer Agency; 1 February 2004.
14. Ken Swenerton, MD. Personal communication. Gynecological Medical Oncologist, BC Cancer Agency Vancouver Centre 2005.
15. B.C. Cancer Agency. SCNAUSEA Protocol Summary. Vancouver, British Columbia: BC Cancer Agency; May 1999.
16. BC Cancer Agency Breast Tumour Group. BCCA Protocol summary for Adjuvant Therapy for Breast Cancer using Doxorubicin and Cyclophosphamide followed by Paclitaxel (Taxol). Vancouver: BC Cancer Agency; BRAJACT, 2005.
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