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Drugs List
Therapeutic Indications
Dosage
Administration
Contraindications
Precautions and Warnings
Pregnancy and Lactation
Side Effects
Monograph

Therapeutic Indications

Uses

Advanced or metastatic non-small cell lung cancer after chemotherapy failed
Advanced/metastatic breast cancer after previous cytotoxic therapy failure
Advanced/metastatic breast cancer in combination with doxorubicin
Advanced/metastatic non-small cell lung cancer - combination with cisplatin
Locally advanced head & neck cancer with cisplatin & 5-fluorouracil
Metastatic breast cancer in patients whose tumours overexpress HER2
Metastatic gastric adenocarcinoma combined with cisplatin & 5-fluorouracil
Operable breast cancer in combination with doxorubicin and cyclophosphamide
Treatment of hormone refractory metastatic prostate cancer

Adjuvant treatment of operable node-positive breast cancer in combination with doxorubicin and cyclophosphamide.

Adjuvant treatment of operable node-negative breast cancer in combination with doxorubicin and cyclophosphamide. Restricted to patients eligible to receive chemotherapy according to internationally established criteria for primary therapy of early breast cancer.

Treatment of locally advanced or metastatic breast cancer in combination with doxorubicin for patients who have not previously received cytotoxic therapy for this condition.

As monotherapy for the treatment of locally advanced or metastatic breast cancer after failure of cytotoxic therapy (previous treatment should have included an anthracycline or an alkylating agent).

Treatment of metastatic breast cancer in combination with trastuzumab where tumours over express HER2, in patients who have not previously received cytotoxic therapy for metastatic disease.

Treatment of locally advanced or metastatic breast cancer in combination with capecitabine after failure of cytotoxic therapy (previous treatment should have included an anthracycline).

Treatment of locally advanced or metastatic non-small cell lung cancer where previous chemotherapy has failed.

Treatment of unresectable, locally advanced or metastatic non-small cell lung cancer in combination with cisplatin in patients who have not previously received chemotherapy for this condition.

Treatment of hormone refractory metastatic prostate cancer in combination with prednisone or prednisolone.

Treatment of metastatic gastric adenocarcinoma (including adenocarcinoma of the gastro-oesophageal junction) in combination with cisplatin and 5-fluorouracil in patients who have not received prior chemotherapy for metastatic disease.

Induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck in combination with cisplatin and 5-fluorouracil.

Dosage

Patients with Hepatic Impairment
Additional Dosage Information

For patients with ALT and/or AST greater than 1.5 times the upper limit of the normal range (ULN) and alkaline phosphatase greater than 2.5 times the ULN, it is recommended to reduce the dose from 100 mg/square metre to 75 mg/square metre (based on docetaxel as monotherapy).

Manufacturer's advise that for patients with serum bilirubin greater than ULN and/or ALT and AST greater than 3.5 times the ULN, with concurrent alkaline phosphatase greater than 6 times the ULN, docetaxel should not be used unless strictly indicated.

Manufacturer's advise that for patients receiving docetaxel in combination with cisplatin and 5-fluorouracil for gastric adenocarcinoma, with elevated ALT and/or AST greater than 1.5 times the ULN range, alkaline phosphatase greater than 2.5 times ULN and bilirubin greater than 1 times ULN, no dosage reduction can be recommended and docetaxel should not be used unless strictly indicated.

Due to limited data, no recommendations are made concerning the treatment of patients with hepatic impairment receiving docetaxel in combination therapy.

In the case of febrile neutropenia, severe neutropenia (less than 500 cells/cubic millimetre for 7 days or more), severe (or cumulative) cutaneous reactions or severe peripheral neuropathy; a reduction in dose for subsequent courses of therapy, is recommended. The dose should be reduced from 100 to 75 mg/square metre and/or from 75 to 60 mg/square metre. If reactions continue at this lowest dose, the treatment should be discontinued.

Adjuvant therapy for breast cancer:

Primary G-CSF prophylaxis should be considered according to the neutropenic risk of the patient for patients receiving docetaxel, doxorubicin and cyclophosphamide in combination. Patients who experience febrile neutropenia or neutropenic infection should have their docetaxel reduced to 60 mg/square metre for all subsequent cycles.
Patients who experience grade 3 or 4 stomatitis, should have their docetaxel reduced to 60 mg/square metre.

In combination with cisplatin

: (see prescribing information for cisplatin)
For patients initially receiving 75 mg/square metre docetaxel, whose nadir of platelet count during the previous course of therapy is less than 25,000 cells/cubic millimetre, or for patients who experience febrile neutropenia or serious non-haematologic toxicities, the dose for subsequent cycles should be reduced to 65 mg/square metre.

In combination with capecitabine:

(see prescribing information for capecitabine)
For patients experiencing the first appearance of a Grade 2 toxicity, which persists at the next cycle treatment, treatment should be delayed until the toxicity is resolved (Grade 0 to 1), when treatment may be resumed at 100% of the original dose.

For patients developing the second appearance of a Grade 2 toxicity, or the first appearance of a Grade 3 toxicity, at any time during the treatment cycle, treatment should be delayed until the toxicity is resolved (Grade 0 to 1), when treatment may be resumed at 55 mg/square metre docetaxel.
For any subsequent appearances of toxicities, or any Grade 4 toxicities, docetaxel should be discontinued.

In combination with trastuzumab:

(see prescribing information for trastuzumab)
In pivotal trials docetaxel was administered the day following the first dose of trastuzumab and immediately after the subsequent doses of trastuzumab, if the preceding dose of trastuzumab was well tolerated.

In combination with cisplatin and 5-fluorouracil:

If an episode of febrile neutropenia, prolonged neutropenia or neutropenic infection occurs despite G-CSF use, the docetaxel dose should be reduced from 75 to 60 mg/square metre. If subsequent episodes of complicated neutropenia occur, the dose should be reduced from 60 to 45 mg/square metre. If grade 4 thrombocytopenia develops the docetaxel dose should be reduced from 75 to 60 mg/square metre.

Subsequent cycles should not be administered until neutrophils recover to a level greater than 1,500 cells/cubic millimetre and platelets recover to greater than 100,000 cells/cubic millimetre. Discontinue permanently if toxicities persist.

Diarrhoea grade 3, 1st episode: reduce 5-fluorouracil dose by 20%
Diarrhoea grade 3, 2nd episode: reduce the docetaxel dose by 20%

Diarrhoea grade 4, 1st episode: reduce dose of both docetaxel and fluorouracil by 20%
Diarrhoea grade 4, 2nd episode: discontinue treatment

Stomatitis/mucositis grade 3, 1st episode: reduce 5-fluorouracil dose by 20%
Stomatitis/mucositis grade 3, 2nd episode: stop 5-fluorouracil treatment, at all subsequent cycles
Stomatitis/mucositis grade 3, 3rd episode: reduce the docetaxel dose by 20%

Stomatitis/mucositis grade 4, 1st episode: stop 5-fluorouracil treatment, at all subsequent cycles
Stomatitis/mucositis grade 4, 2nd episode: reduce the docetaxel dose by 20%

A pivotal trial in squamous cell carcinoma of the head and neck recommended the use of G-CSF on days 6 to 15 on all subsequent cycles in patients experiencing complicated neutropenia.

Concomitant use with strong CYP3A4 inhibitors

The concomitant use of docetaxel with strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, clarithromycin) should be avoided.

Precautions and Warnings

Ascites
Patients over 60 years
Alcoholism
Epileptic disorder
Hepatic impairment
Pericardial effusion
Significant pleural effusion

Reduce dose in patients with hepatic impairment
Advise ability to drive/operate machinery may be affected by side effects
Give pre-treatment counselling and consideration of sperm cryopreservation
Pre-medication with an oral corticosteroid recommended before treatment
Prophylactic G-CSF should be considered
Treatment to be initiated and supervised by a specialist
Contains alcohol
Contains polysorbate
Consult local policy on the safe use of anti-cancer drugs
Never rechallenge treatment after a severe hypersensitivity reaction
Resuscitation facilities must be immediately available
Staff: Not to be handled by pregnant staff
Monitor cardiac function prior to, during and following up from treatment
Monitor hepatic function before treatment and regularly during treatment
If visual disturbances occur, perform ophthalmic evaluation
Monitor for hypersensitivity reactions-particularly 1st and 2nd infusions
Monitor haematological parameters periodically
Monitor patients with severe fluid retention closely
Patients with new pulmonary symptoms should be investigated
Reduce dose if neutrophil count < 500 cells/cubic mm for more than 7 days
Advise patient to report abdominal pain or tenderness, fever or diarrhoea
Advise patient to report any new or worsening respiratory symptoms
Reduce dose if grade 3 or 4 gastrointestinal toxicities occur
Reduce dose if severe peripheral neurotoxicity occurs
Risk of myelodysplasia/myeloid leukaemia requires haematological follow-up
Discontinue if generalised rash or erythema occurs
Discontinue if macular oedema occurs
Discontinue if severe hypersensitivity reactions occur
Discontinue immediately if severe hypotension occurs
Suspend treatment if patients experience worsening of respiratory symptoms
Advise patient grapefruit products may increase plasma level
May cause impaired fertility
Female: Contraception required during and for 3 months after treatment
Male: Contraception required during and for 6 months after treatment

Pre-medication with an oral corticosteroid is recommended, unless contraindicated. This should help to reduce incidence and severity of fluid retention, and severity of any hypersensitivity reaction. For breast cancer, gastric cancer, head and neck cancer and non-small cell lung cancer, dexamethasone 16 mg daily (e.g. 8 mg twice daily) for 3 days, starting one day before docetaxel administration may be used. For prostate cancer where prednisone or prednisolone forms part of the regimen, the recommended premedication regime is 8 mg of dexamethasone 12 hours, 3 hours and 1 hour before the infusion.

Neutropenia is the most frequent adverse effect seen during docetaxel therapy. Neutrophil nadirs occurred at a median of 7 days, but could appear earlier in heavily pre-treated patients. Blood counts should be monitored frequently for all patients receiving docetaxel. Patients should be retreated with docetaxel when neutrophils recover to a level equal to or greater than 1,500 cells/cubic millimetre.

Cardiac failure has been seen in patients treated with docetaxel and trastuzumab (especially after anthracycline containing chemotherapy). This may be moderate to severe and has been associated with fatalities. Eligible patients for combination treatment (docetaxel and trastuzumab) should have their cardiac function assessed prior to, every 3 months during treatment and in the follow up period.

Pregnancy and Lactation

Pregnancy

Docetaxel is contraindicated during pregnancy.

Docetaxel may cause foetal harm when administered to pregnant women.

There is little information on the use of docetaxel in pregnant women, but it has been shown to be embryotoxic and foetotoxic in rabbits and rats.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Breastfeeding is contraindicated during docetaxel therapy.

It is not known whether docetaxel is excreted in human breast milk, but due to the potential for serious adverse reactions in nursing infants, breastfeeding must be discontinued for the duration of docetaxel therapy.

Schaefer recommends withholding breastfeeding for 48 hours, however, the effect of concurrent therapies must also be considered.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Presentation

Infusions of docetaxel

Drugs List

docetaxel 160mg/16ml concentrate for solution for infusion

docetaxel 160mg/8ml concentrate for solution for infusion

docetaxel 20mg/1ml concentrate for solution for infusion

docetaxel 20mg/2ml concentrate for solution for infusion

docetaxel 80mg/4ml concentrate for solution for infusion

docetaxel 80mg/8ml concentrate for solution for infusion