Usual Adult Dose for Non-Small Cell Lung Cancer

As a single agent after failure of prior platinum-based chemotherapy: 75 mg/m2 IV over 1 hour every 3 weeks

Chemotherapy-naive patients: 75 mg/m2 IV over 1 hour immediately followed by cisplatin 75 mg/m2 IV over 30 to 60 minutes; repeat every 3 weeks

Comments:

• Premedicate with oral corticosteroids (e.g., dexamethasone 8 mg 2 times a day) for 3 days starting 1 day prior to chemotherapy.
• Adjust dose as needed for toxicity.
• Patients should receive cisplatin premedication with antiemetics and hydration.

Uses:

• As monotherapy for locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of prior platinum-based chemotherapy
• In combination with cisplatin for unresectable, locally advanced or metastatic NSCLC in patients who have not previously received chemotherapy for this condition

Usual Adult Dose for Breast Cancer

• Monotherapy: 60 to 100 mg/m2 IV over 1 hour every 3 weeks
• Adjuvant therapy: 75 mg/m2 IV over 1 hour administered 1 hour after doxorubicin 50 mg/m2 IV and cyclophosphamide 500 mg/m2 IV every 3 weeks for 6 cycles; prophylactic G-CSF may be used to mitigate the risk of hematological toxicities

Comments:

• Premedicate with oral corticosteroids (e.g., dexamethasone 8 mg 2 times a day) for 3 days starting 1 day prior to chemotherapy.
• Adjust dose as needed for toxicity.

Uses:

• As a single agent for locally advanced or metastatic breast cancer after failure of prior chemotherapy
• In combination with doxorubicin and cyclophosphamide for operable node-positive breast cancer

Usual Adult Dose for Gastric Cancer

75 mg/m2 IV over 1 hour followed by cisplatin 75 mg/m2 IV over 1 to 3 hours (both on Day 1 only), followed by fluorouracil 750 mg/m2 daily given as a 24-hour continuous IV infusion for 5 days, starting at the end of the cisplatin infusion; repeat every 3 weeks

Comments:

• Premedicate with oral corticosteroids (e.g., dexamethasone 8 mg 2 times a day) for 3 days starting 1 day prior to chemotherapy.
• Adjust dose as needed for toxicity.
• Patients should receive cisplatin premedication with antiemetics and hydration.

Use: In combination with cisplatin and fluorouracil for advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, in patients who have not received prior chemotherapy

Usual Adult Dose for Head and Neck Cancer

Induction therapy of locally advanced inoperable SCCHN:

• Day 1: 75 mg/m2 IV over 1 hour followed by cisplatin 75 mg/m2 IV over 1 hour, on Day 1, followed by fluorouracil 750 mg/m2 as a continuous IV infusion daily for 5 days
• Administer this regimen every 3 weeks for 4 cycles.
• Following chemotherapy, patients should receive radiotherapy.

Induction therapy for locally advanced (unresectable, low surgical cure, or organ preservation) SCCHN:

• Day 1: 75 mg/m2 IV over 1 hour followed by cisplatin 100 mg/m2 administered as a 30-minute to 3-hour IV infusion, followed by fluorouracil 1000 mg/m2/day as a continuous IV infusion from Day 1 to Day 4
• Repeat therapy every 3 weeks for 3 cycles.
• Following chemotherapy, patients should receive chemoradiotherapy.

Comments:

• Premedicate with oral corticosteroids (e.g., dexamethasone 8 mg orally 2 times a day) for 3 days starting 1 day prior to chemotherapy.
• Adjust dose as needed for toxicity.
• Patients should receive cisplatin premedication with antiemetics and hydration.
• Prophylaxis for neutropenic infections should be administered; during clinical trials, all patients received prophylactic antibiotics.

Use: In combination with cisplatin and fluorouracil for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN)

Usual Adult Dose for Prostate Cancer

75 mg/m2 IV over 1 hour every 3 weeks; prednisone 5 mg orally 2 times a day is administered continuously

Comments:

• For hormone-refractory metastatic prostate cancer, because of the concurrent use of prednisone, the recommended premedication regimen is dexamethasone 8 mg orally, at 12 hours, 3 hours, and 1 hour before docetaxel.

Use: In combination with prednisone for androgen independent (hormone refractory) metastatic prostate cancer

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

• Patients with bilirubin greater than the upper limit of normal (ULN) should not receive this drug.
• Patients with AST and/or ALT greater than 1.5 x ULN concomitant with alkaline phosphatase greater than 2.5 x ULN should not receive this drug.

Gastric or Head and Neck Cancer - In Combination with Cisplatin and Fluorouracil
The following dose adjustments were used during clinical trials:

• For AST/ALT elevations greater than 12.5 x ULN to less than or equal to 5 x ULN and alkaline phosphatase (AP) elevations of 2.5 x ULN or less: docetaxel dose reduced by 20%
• For AST/ALT elevations greater than 1.5 x ULN to less than or equal to 5 x ULN and AP elevations greater than 2.5 x ULN to less than or equal to 5 x ULN: docetaxel dose reduced by 20%
• For AST or ALT elevations greater than 5 X ULN and/or AP elevations greater than 5 x ULN: docetaxel was stopped.

Dose Adjustments

Do not initiate this drug until neutrophil count recovers to a level greater than 1500 cells/mm3 and platelets recover to a level greater than 100,000 cells/mm3.

Hematologic Toxicity:

• Following severe neutropenia (less than 500 cells/mm3) lasting 7 days or more, febrile neutropenia, or a grade 4 infection during a cycle; reduce docetaxel dose by 25% in subsequent cycles.

Breast Cancer - Monotherapy:

• For patients initially dosed at 100 mg/m2 and experiencing febrile neutropenia, neutrophils less than 500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions, or severe peripheral neuropathy during therapy, reduce dose to 75 mg/m2; if these reactions persist, consider a further reduction to 55 mg/m2 or treatment discontinuation.
• For patients initiated at 60 mg/m2 who do not experience febrile neutropenia, neutrophils less than 500 cells/mm3 for more than 1 week, severe or cumulative cutaneous reactions, or severe peripheral neuropathy may tolerate higher doses. Patients who develop Grade 3 or greater peripheral neuropathy should have therapy discontinued.
• For patients developing Grade 3 or greater peripheral neuropathy, therapy should be discontinued.

Breast Cancer - Combination with Doxorubicin and Cyclophosphamide

• Patients experiencing febrile neutropenia should receive G-CSF in all subsequent cycles; for persistent febrile neutropenia, patients should remain on G-CSF and reduce their docetaxel dose to 60 mg/m2.
• For grade 3 or 4 stomatitis: Reduce docetaxel dose to 60 mg/m2.
• For severe or cumulative cutaneous reactions or moderate neurosensory signs and/or symptoms: Reduce dose to 60 mg/m2; if reactions persist at 60 mg/m2, therapy should be discontinued.

Non-small Cell Lung Cancer (NSCLC) - Monotherapy:

• For patients initially dosed at 75 mg/m2 and experiencing febrile neutropenia, neutrophils less than 500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions, or other Grade 3 or 4 nonhematologic toxicities: withhold treatment until resolution of the toxicity and then resume at 55 mg/m2.
• Patients developing a Grade 3 or greater peripheral neuropathy should have docetaxel treatment discontinued.

Non-small Cell Lung Cancer (NSCLC) - Combination Therapy:

• For patients initially dosed at 75 mg/m2 in combination with cisplatin and experiencing a platelet nadir count of less than 25,000 cells/mm3, febrile neutropenia, and/or serious nonhematologic toxicities, reduce docetaxel dose in subsequent cycles to 65 mg/m2. A further dose reduction to 50 mg/m2 may be undertaken if necessary. See prescribing information for cisplatin dose adjustments.

Prostate Cancer:

• Patients experiencing febrile neutropenia, neutrophils less than 500 cells/mm3 for more than one week, severe or cumulative cutaneous reactions, or moderate neurosensory signs and/or symptoms should have their docetaxel dose to 60 mg/m2; if patient continues to experience these reactions at 60 mg/m2, therapy should be discontinued.

Gastric or Head and Neck Cancer - In Combination with Cisplatin and Fluorouracil:

• For febrile neutropenia, or documented infection with neutropenia, or neutropenia lasting more than 7 days, initiate G-CSF and continue G-CSF in subsequent cycles; if an episode of febrile neutropenia, prolonged neutropenia, or neutropenic infection occurs despite G-CSF use, reduce docetaxel dose to 60 mg/m2; if subsequent episodes of complicated neutropenia occur, the docetaxel dose should be reduced to 45 mg/m2.
• Grade 4 thrombocytopenia: reduce docetaxel dose to 60 mg/m2; platelets should recover to a level greater than 100,000 cells/mm3 prior to retreatment.
• Therapy should be discontinued if neutrophils do not recover to greater than 1500 cells/mm3 and platelets do not recover to greater than 100,000 cells/mm3.

Fluorouracil Dose Modifications and Delays used in the Gastric Cancer Study:

• Grade 2 or greater plantar-palmar toxicity: stop fluorouracil until recovered, then reduce dose by 20%
• Grade 3 toxicities except alopecia and anemia: delay chemotherapy until resolution to grade 1 or less (maximum delay should be 2 weeks from planned date of infusion), recommence if medically appropriate.
• For other fluorouracil dosage adjustments, see fluorouracil prescribing information.

Dose modifications in Combination with Cisplatin and 5-fluorouracil:
DIARRHEA GRADE 3:

• First episode: Reduce the dose of 5-fluorouracil by 20%.
• Second episode: Then reduce the docetaxel dose by 20%.

DIARRHEA GRADE 4:

• First episode: Reduce the dose of both docetaxel and fluorouracil by 20%.
• Second episode: Discontinue therapy.

STOMATITIS/MUCOSITIS GRADE 3:

• First episode: Reduce fluorouracil dose by 20%.
• Second episode: Stop 5-fluorouracil only at all subsequent cycles.
• Third episode: Reduce docetaxel dose by 20%.

STOMATITIS/MUCOSITIS GRADE 4:

• First episode: Stop 5-fluorouracil only at all subsequent cycles.
• Second episode: Reduce docetaxel dose by 20%.

Strong CYP450 3A4 Inhibitors:

• Avoid use of concomitant strong CYP450 3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole); if concomitant use is unavoidable, the docetaxel dose may require adjustment.

Precautions

US BOXED WARNINGS:
Toxic Deaths:

• Increased incidence of treatment-related mortality associated with use in patients with abnormal liver function, use at higher doses, and in patients with non-small cell lung cancer (NSCLC) and prior platinum-based-therapy who received docetaxel at 100 mg/m2.

Hepatotoxicity:

• This drug should not be given to patients with bilirubin levels above the upper limit of normal or to patients with AST and/or ALT levels greater than 1.5 times the upper limit of normal (1.5 x ULN) concomitant with alkaline phosphatase greater than 2.5 x ULN.
• Grade 4 neutropenia, febrile neutropenia, infections, severe thrombocytopenia, severe stomatitis, severe skin toxicity, and toxic death are associated with bilirubin elevations and with transaminase abnormalities concurrent with alkaline phosphatase elevations; isolated transaminase elevations greater than 1.5 x ULN also had a higher rate of grade 4 febrile neutropenia but was not associated with an increased incidence of toxic death.
• Bilirubin, AST or ALT, and alkaline phosphatase levels should be obtained prior to each treatment cycle.

Neutropenia:

• Neutropenia may be severe and result in infection.
• Perform frequent blood cell counts to monitor for the occurrence of neutropenia; do not give this drug to patients with neutrophil counts less than 1500 cells/mm3.

Hypersensitivity Reactions:

• Severe hypersensitivity reactions characterized by generalized rash/erythema, hypotension and/or bronchospasm, or very rarely fatal anaphylaxis, have been reported in patients who have received a 3-day dexamethasone premedication; immediate discontinuation and administration of appropriate therapy is required for severe hypersensitivity reactions.
• Do not administer this drug to patients with a history of severe hypersensitivity reactions to docetaxel or other drugs formulated with polysorbate 80.

Fluid Retention:

• Severe fluid retention occurred in 6.5% (6/92) of patients despite a 3-day dexamethasone premedication regimen; events included poorly tolerated peripheral edema, generalized edema, pleural effusion requiring urgent drainage, dyspnea at rest, cardiac tamponade, and pronounced abdominal distension due to ascites.

CONTRAINDICATIONS:

• Hypersensitivity to the active component or any of the ingredients
• Baseline neutrophil count of less than 1.5 cells x 10(9)/L

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Administer in a facility equipped to manage possible complications, e.g. anaphylaxis.
• Administer IV over 1 hour every 3 weeks; dosages will vary depending on indication.
• Do not use PVC equipment as the plasticizer (di-2-ethylhexyl phthalate; DEHP) may be leached.
• If the drug contacts skin or mucosa, immediately and thoroughly wash with water.

Storage requirements:

• Store lyophilized vials in refrigerator between 2C and 8C (36F to 46F); once reconstituted with provided diluent, stable for 8 hours.
• Store solution for IV infusion between 2C and 25C (36F to 77F); once punctured, stable for 28 days.

Reconstitution/preparation techniques:

• Procedures for proper handling and disposal of anticancer drug should be followed.
• Must dilute prior to administration; do not exceed a concentration of 0.74 mg/mL.
• Stable in NS or D5W for 4 hours between 2C and 25C (36F and 77F); use within 4 hours including storage and administration.
• Refer to manufacturer product information for specifics.

General:

• Therapy should be initiated by a physician experienced in the administration of anti-cancer agents.
• All patients should receive premedication with oral corticosteroids to reduce the incidence and severity of fluid retention and the severity of hypersensitivity reactions.
• Patients treated with docetaxel in combination with cisplatin and fluorouracil must receive antiemetics and appropriate hydration according to current institutional guidelines.

Monitoring:

• Perform frequent peripheral blood cell counts
• Obtain LFTs (bilirubin, AST or ALT, and alkaline phosphatase) prior to each cycle
• Monitor for febrile neutropenia and neutropenic infection
• Monitor for fluid retention

Patient advice:

• Advise patient to use effective contraception during therapy and following therapy; if pregnancy is suspected, patients should seek medical advice and counseling.
• Advise patient about the importance of premedication.
• Patients should immediately report signs of hypersensitivity.
• Have patients watch for and report signs of fluid retention.
• Instruct patients to monitor their temperature and report fever.
• Explain to patients that side effects of nausea, vomiting, diarrhea, constipation, fatigue, excessive tearing, infusion site reactions, and hair loss may occur; have patients report myalgia, cutaneous, or neurologic reactions.