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DOCEtaxel
Docetaxel acts by disrupting the microtubular network in cells that is essential for cell division. It promotes the assembly of tubulin into stable microtubules, while simultaneously inhibiting their disassembly. This leads to the stabilization of microtubules, resulting in the inhibition of mitosis in cells.
Linear, dose dependent pharmacokinetics. Exposure is dose proportional and disposition is triphasic following 70-115 mg/m2. Highest concentrations were found in the liver, bile and intestine.
| Cross blood brain barrier? | No |
| PPB | > 95 % |
Docetaxel is metabolized primarily by the cytochrome P450-3A enzymes.
| Active metabolites | no |
| Inactive metabolites | yes |
Docetaxel is mainly excreted into feces via the bile.
| Urine | 6% |
| Feces |
75%, mostly as inactive metabolites |
| Half-life |
11 hours (terminal) |
- Locally advanced or metastatic breast carcinoma as 1) a single agent; 2) in combination with capecitabine after failure of prior anthracycline chemotherapy; 3) in combination with doxorubicin as first-line therapy, for patients with potentially life-threatening disease (such as visceral or lung metastatic disease)
- Locally advanced or metastatic non-small cell lung cancer in monotherapy or in combination with platinum agents
- Recurrent and/or metastatic squamous cell carcinoma of the head and neck as monotherapy after the failure of prior chemotherapy
- Metastatic carcinoma of the ovary after failure of first-line or subsequent chemotherapy
- Androgen-independent (hormone-refractory) metastatic prostate cancer in combination with prednisone (or prednisolone)
- Adjuvant treatment in patients with operable node-positive breast cancer in combination with doxorubicin and cyclophosphamide
Other Uses:
- Gastroesophageal cancer
- Bladder/urothelial cancer
- Gynecological sarcoma
- Soft tissue sarcoma
Emetogenic Potential:
Extravasation Potential: Irritant
The following table contains adverse effects reported mainly in docetaxel monotherapy for breast, lung and ovarian cancer.
| ORGAN SITE | SIDE EFFECT* (%) | ONSET** | |||
|---|---|---|---|---|---|
| Cardiovascular | Arrhythmia (2%) | I | |||
| Arterial thromboembolism (rare) | E | ||||
| Cardiotoxicity (<1%) | I | ||||
| Hypertension (2%) | I | ||||
| Venous thromboembolism (rare) | E | ||||
| Dermatological | Alopecia (76%) (rarely permanent) | E | |||
| Hand-foot syndrome (rare) | E | ||||
| Nail disorder (31%) (severe 3%) | E D | ||||
| Radiation recall reaction and injection site recall reaction | |||||
| Rash (48%) (5% severe) | E D | ||||
| Gastrointestinal | Colitis (rare, may be severe) | E | |||
| Diarrhea (39%) (may be severe) | E | ||||
| GI obstruction (rare) | E | ||||
| GI perforation (rare) | E | ||||
| Mucositis (42%) (severe 6%) | E | ||||
| Nausea, vomiting (39%) | I | ||||
| General | Fatigue (62%) (severe 13%) | E | |||
| Fluid retention (47%) (with pre-medication; severe 7%) | I D | ||||
| Hematological | Disseminated intravascular coagulation (rare) | E | |||
| Myelosuppression ± infection, bleeding (75%) (severe) | E | ||||
| Hepatobiliary | ↑ LFTs (<5%) (may be severe) | E | |||
| Hypersensitivity | Hypersensitivity (21%) (severe 4%) | I | |||
| Injection site | Injection site reaction (6%) | I | |||
| Musculoskeletal | Musculoskeletal pain (19%) | E | |||
| Neoplastic | Leukemia (secondary) (AML, MDS) | D | |||
| Nervous System | Cognitive disturbance (rare) | E | |||
| Neuropathy (49%) (severe 4%) | E D | ||||
| Seizure (rare) | E | ||||
| Ophthalmic | Cystoid macular edema | E | |||
| Eye disorders (transient visual disturbance - rare) | E | ||||
| Other (lacrimal duct obstruction) | E | ||||
| Watering eyes | E | ||||
| Renal | Renal failure (rare, concurrent nephrotoxic drugs) | E | |||
| Respiratory | Acute respiratory distress syndrome (ARDS) (rare) | E | |||
| Dyspnea (5%) (with prednisone in prostate cancer) | E | ||||
| Pneumonitis (rare, also reported in combination with radiotherapy) | E | ||||
* "Incidence" may refer to an absolute value or the higher value from a reported range.
"Rare"
may refer to events with < 1% incidence, reported in post-marketing, phase 1 studies,
isolated data or anecdotal
reports.
** I = immediate (onset in hours to days)
E = early (days to weeks)
D = delayed (weeks to months)
L = late (months to years)
The most common side effects for DOCEtaxel include alopecia, myelosuppression, fatigue, neuropathy, skin/nail effects, fluid retention, mucositis, diarrhea, nausea/vomiting and hypersensitivity.
The major dose-limiting adverse effect of docetaxel is myelosuppression. Febrile neutropenia occurs in 11%; this may be fatal in 1% of cases. When associated with enterocolitis, it may be life-threatening or fatal.
Severe hypersensitivity reactions characterized by hypotension, bronchospasm or generalized rash/erythema may occur within a few minutes of docetaxel infusions and may potentially be fatal. All patients receiving docetaxel should be pre-medicated with oral dexamethasone and should be observed closely for hypersensitivity reactions, especially during the first and second infusions. Patients who are hypersensitive to paclitaxel are at an increased risk. Depending on the severity of the symptoms, appropriate treatment for sensitivity reactions associated with docetaxel may include a decrease in the rate of the infusion, immediate interruption of the infusion, IV administration of diphenhydramine with or without dexamethasone and/or epinephrine as needed, pre-medication with an oral or IV antihistamine prior to the next cycle of docetaxel, or discontinuance of docetaxel therapy. Patients who experience severe hypersensitivity reactions should not be re-challenged.
Diarrhea, nausea and vomiting are common, may be severe and may be associated with electrolyte disturbances.
Docetaxel-induced fluid retention is cumulative in severity and incidence, generally reversible but may be severe with ascites, pleural or pericardial effusions. Premedication decreases the severity of fluid retention, and all patients should receive premedication. Use with caution in patients with existing effusions and ascites.
Cutaneous reactions are dose-dependent and cumulative, characterized by a rash, including localized eruptions mainly on feet and hands (palmar-plantar dysesthesia), but also on arms, face or thorax, and may be associated with pruritus. Eruptions generally occur within 1 week following the docetaxel infusion, and usually resolve before the next infusion. Therapy for erythrodysesthesia has generally been symptomatic. Severe nail disorder (cumulative) may occur. Alopecia is dose-related but may be permanent.
Musculoskeletal manifestations usually are transient, occurring within a few days after docetaxel administration lasting about 4 days.
Docetaxel can cause a dose-related reversible sensory neuropathy. Severe symptoms are less common but require dose modifications.
Cystoid macular edema (CME) has been reported in docetaxel-treated patients, as well as with other taxanes. Patients who present with impaired vision during docetaxel treatment should undergo a prompt ophthalmologic examination. Docetaxel associated CME may not be associated with vascular leakage. CME is usually reversible upon taxane discontinuation; treatment for CME may be required in some cases.
Weekly docetaxel regimens have been tested, but have not been approved by Health Canada. Weekly regimens appear to be associated with a slightly different toxicity profile.
Refer to protocol by which patient is being treated.
Pre-medications (prophylaxis for infusion reaction):
- Dexamethasone* 8 mg PO BID for 3 days, starting 1-day pre-infusion†
An alternative for patients with prostate cancer being treated with prednisone:
- Dexamethasone* 8 mg PO 12 hours, 3 hours, and 1 hour pre-infusion.
* Do not discontinue dexamethasone, even in the absence of an IR, due to the benefits on other adverse effects (e.g. pain and edema).
† Dexamethasone 10-20 mg IV can be given if patient forgot to take oral doses.
Patients should not be treated until they have recovered from prior toxicity and have acceptable blood counts (ANC ≥ 1.5 x 109/L and platelets ≥ 100 x 109/L).
Patients with head and neck cancer are at increased risk of febrile neutropenia and prophylactic antibiotics should be used (i.e. oral fluoroquinolone for 10 days starting on day 5).
Refer to the 2016 CCO Recommendations on G-CSF (prophylaxis of febrile neutropenia in adult patients undergoing systemic treatment)
Monotherapy - Prostate cancer (with prednisone):
Intravenous: 75 mg/m² administered as an 1 hour infusion Every 3 weeks
Monotherapy - All other disease sites:
Intravenous: 75 to 100* mg/m² administered as an 1 hour infusion Every 3 weeks
* Refer to the regimen monographs for dosing in specific disease sites
Combination:
Intravenous: 75 mg/m² administered as an 1 hour infusion Every 3 weeks
|
Toxicity (worst in previous cycle)
|
Modification*
|
||
|
(Previous dose)
|
100mg/m2
|
75mg/m2
|
% of previous dose |
|
Febrile neutropenia / Grade 4 ANC ≥ 7 d |
75mg/m2
(or G-CSF) |
60mg/m2
(or G-CSF) |
75%
|
|
Grade 3 skin/ neuro/ major organ/ non-hematologic toxicity |
75mg/m2
|
60mg/m2
|
75%
|
|
Any occurrence of cystoid macular edema |
Hold and investigate; refer patient promptly an ophthalmic examination. Discontinue if confirmed. |
||
|
Grade 4 skin/ neuro/ major organ/ non-hematologic toxicity OR
Recurrence of Grade 3 toxicity after prior dose reduction |
Discontinue
|
Discontinue
|
Discontinue
|
|
* Do not retreat until ANC ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, and non-hematologic/organ toxicity ≤ grade 2. |
|||
Management of Infusion-related reactions:
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
| Grade | Management | Re-challenge |
| 1 or 2 |
Restart:
|
|
| 3 or 4 |
|
|
Patients with hepatic impairment have a higher risk of severe adverse effects, including fatal gastrointestinal hemorrhage, sepsis and myelosuppression.
| Bilirubin |
AST and/or ALT |
|
Alkaline Phosphatase |
Docetaxel dose |
||
| > ULN | AND | Any | AND | Any |
Do not treat. Discontinue if treatment already started. |
|
| Any | AND |
> 1.5 X ULN
|
AND |
> 2.5 x ULN |
||
No adjustment required.
No adjustment required, but caution should be exercised in elderly patients with poor performance status who are receiving docetaxel. Patients over the age of 60 years appear to have increased toxicity when docetaxel is used in combination with capecitabine, as do patients treated with docetaxel for prostate cancer (>65 years).
Safety and effectiveness in children have not been established.
- Refer to the respective product monographs for preparation instructions. Mix in 250mL D5W or NS to a maximum concentration of 0.3-0.74 mg/mL. For doses over 200 mg, use a larger volume of the infusion vehicle so the maximum concentration is not exceeded.
- Infuse through main IV line over 1 hour.
- In order to minimize patients' exposure to DEHP leaching from PVC bags or sets, use polyolefin or polypropylene infusion bags and polyethylene-lined administration sets.
- To minimize hypersensitivity reactions, docetaxel infusion should be started at a slow rate, then increased incrementally to planned rate.
- Monitor patient for signs of alcohol intoxication (due to alcohol content in formulation) during and after the infusion.
- Injection site recall reactions (recurrence of skin reaction at a previous extravasation site after docetaxel is administered at a different site) have been observed.
Also refer to the CCO guideline for detailed description of Management of Cancer Medication-Related Infusion Reactions.
- Patients who have a history of severe hypersensitivity reactions to docetaxel, to other drugs formulated with polysorbate 80 or polyethylene glycol 300, or to any components of the formulation
- Patients with baseline neutrophil counts of < 1.5 x 109/L
- Patients with severe liver impairment
- Patients with:
- bilirubin > ULN or
- AST and/or ALT > 1.5 x ULN and ALP > 2.5 x ULN or
- ANC < 1.5 x 109/L
- (refer to dose modifications section)
- Use with caution in patients with pre-existing effusions or ascites.
- Use with caution in patients who are hypersensitive to paclitaxel.
- Docetaxel contains ethanol (± 1g/m2; refer to respective product monographs) and may cause drowsiness. Patients should be cautioned regarding driving and the use of machinery immediately after receiving the infusion. Ethanol may be harmful to patients at risk of adverse effects such as those with alcoholism, liver disease, epilepsy and children. Cases of alcohol intoxication have been reported.
Other Drug Properties:
-
Carcinogenicity:
Yes
-
Embryotoxicity:
Yes
-
Fetotoxicity:
Yes
-
Mutagenicity:
Yes
-
Genotoxicity:
Yes
Docetaxel is contraindicated in pregnancy. Adequate contraception must be used by both sexes, during docetaxel treatment and for at least 6 months after the last dose -
Breastfeeding:
Contraindicated
-
Fertility effects:
Probable
Docetaxel is also a substrate of p-glycoprotein. Inducers and inhibitors of p-glycoprotein may potentially affect docetaxel efficacy or increase docetaxel toxicity respectively.
| AGENT | EFFECT | MECHANISM | MANAGEMENT |
|---|---|---|---|
| CYP3A4 inhibitors (i.e. ketoconazole, clarithromycin, ritonavir, fruit or juice from grapefruit, Seville oranges or starfruit) | ↑ docetaxel exposure (up to 2.2 x) and toxicity | ↓ metabolism of docetaxel | Avoid concomitant use; consider docetaxel dose ↓ if must use together (50% for strong inhibitors) |
| Substrates or inducers of CYP3A4 (i.e. cyclosporine, nifedipine, troleandomycin, orphenadrine, testosterone, midazolam) | Alteration of docetaxel pharmacokinetics | Caution | |
| Dronedarone | ↑ docetaxel severe toxicities (case report) | Inhibits Pgp and CYP3A4; delayed clearance of docetaxel | Avoid combination |
| Epirubicin | ↑ systemic exposure to epirubicin or its metabolites. May be schedule dependent. | Docetaxel (or polysorbate 80) is suggested to interact with epirubicin metabolism and/or excretion | Caution if used in combination; give epirubicin first |
| Sorafenib | ↑ docetaxel exposure | Unknown | Caution; monitor for toxicity |
| CNS depressants (e.g. benzodiazepines, opioids) | ↑ risk of CNS depression | Additive due to ethanol in docetaxel formulations | Caution; monitor for intoxication during and after infusions |
Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.
| Monitor Type | Monitor Frequency |
|---|---|
CBC, including nadir counts |
Baseline and before each dose |
Liver function tests |
Baseline and before each cycle |
Clinical toxicity assessment of infection, bleeding, neurotoxicity, fluid retention, hypersensitivity, lethargy, cutaneous reactions, thromboembolism, cardiovascular, musculoskeletal pain, ophthalmic, GI, respiratory effects or enterocolitis especially in the setting of neutropenia |
At each visit |
Grade toxicity using the current NCI-CTCAE (Common Terminology Criteria for Adverse Events) version
Berthold DR, Pond GR, Soban F et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer: updated survival in the TAX327 study. J Clin Oncol 2008;26(2):242-5.
Ceruti M, Tagini V, Recalenda V, et al. Docetaxel in combination with epirubicin in metastatic breast cancer: pharmacokinetic interactions. Il Farmaco 1999;54:733–9.
Esposito M, Venturini M, Vannozzi MO, et al. Comparative effects of paclitaxel and docetaxel on the metabolism and pharmacokinetics of epirubicin in breast cancer patients. J Clin Oncol 1999;17:1132-40.
Martin M, Pienkowski T, Mackey J, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 2005;352(22):2302-13.
McEvoy GK, editor. Docetaxel: AHFS Drug Information 2011. Bethesda: American Society of Health-System Pharmacists.
Prevezas C, Matard B, Pinquier L, et al. Irreversible and severe alopecia following docetaxel or paclitaxel cytotoxic therapy for breast cancer. British Journal of Dermatology 2009;160(4):883-5.
Product Monograph: Nexavar® (sorafenib). Bayer Inc., April 4, 2012.
Product Monograph: Taxotere® (Docetaxel). Sanofi-aventis Canada, November 3, 2017.
Rivera E, Mejia JA, Arun BK et al. Phase 3 study comparing the use of docetaxel on an every-3-week versus weekly schedule in the treatment of metastatic breast cancer. Cancer 2008;112:1455–61.
Scripture CD, Figg WD. Drug interactions in cancer therapy. Nat Rev Cancer 2006;6(7):546-58.
Stemmler HJ, Harbeck N, Gröll de Rivera I, et al. Prospective multicenter randomized phase III study of weekly versus standard docetaxel (D2) for first-line treatment of metastatic breast cancer. Oncology 2010;79(3-4):197-203.
Schröder CP, de Munck L, Westermann AM, et al. Weekly docetaxel in metastatic breast cancer patients: no superior benefits compared to three-weekly docetaxel. Eur J Cancer 2011;47(9):1355-62.
Tannock IF, de Wit R, Berry W, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004;351(15):1502-12.
Vodovar D, Mongardon N, Moachon L, et al. Severe docetaxel overdose induced by pharmacokinetic interaction with dronedarone. J Clin Oncol 2011;29(24):e694-5.
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