Docetax Special Precautions

General: All patients should be premedicated with an oral corticosteroid such as dexamethasone prior to docetaxel administration to reduce the incidence and severity of fluid retention as well as the severity of hypersensitivity reactions.
Toxic Deaths: Docetaxel has been associated with deaths considered possibly or probably related to treatment in patients with metastatic breast cancer. These were patients who are previously treated or untreated, with normal baseline liver function and those with various tumor types who had abnormal baseline liver function. Almost half of the accounted deaths occurred during the first cycle with sepsis as the major cause.
Deaths were also reported in patients with locally advanced or metastatic NSCLC who had a history of prior platinum-based chemotherapy.
Acute Myeloid Leukemia: In clinical trials, treatment-related acute myeloid leukemia (AML) or myelodysplasia have occurred in patients receiving docetaxel, doxorubicin and cyclophosphamide. These patients require hematological follow-up.
Fluid Retention: Patients with severe fluid retention such as pleural effusion, pericardial effusion and ascites should be monitored closely.
Hematological Effects: Perform frequent peripheral blood cell counts on all patients receiving docetaxel. Patients should not be retreated with subsequent cycles of docetaxel until neutrophils recover to a level of >1,500 cells/mm³ and platelets recover to a level >100,000 cells/mm³. A 25% reduction in the dose of docetaxel is recommended during subsequent cycles following severe neutropenia (<500 cells/mm³) lasting 7 days or more, febrile neutropenia, or a grade 4 infection in a docetaxel cycle.
In patients treated with docetaxel in combination with cisplatin and 5-fluorouracil (TCF), febrile neutropenia and neutropenic infection occurred at lower rates when patients received prophylactic G-CSF. Patients treated with TCF should receive prophylactic G-CSF to mitigate the risk of complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TCF should be closely monitored.
In patients treated with docetaxel in combination with doxorubicin and cyclophosphamide (TAC), febrile neutropenia and/or neutropenic infection occurred at lower rates when patients received primary G-CSF prophylaxis. Primary G-CSF prophylaxis should be considered in patients who receive adjuvant therapy with TAC for breast cancer to mitigate the risk of complicated neutropenia (febrile neutropenia, prolonged neutropenia or neutropenic infection). Patients receiving TAC should be closely monitored.
Neutropenia (<2,000 neutrophils/mm³) occurs in all patients given 60 mg/m² to 100 mg/m² of docetaxel and grade 4 neutropenia (<500 cells/mm³) occurs in 85% of patients given 100 mg/m² and 75% of patients given 60 mg/m². Frequent monitoring of blood counts is, therefore, essential so that dose can be adjusted. Docetaxel should not be administered to patients with neutrophils <1,500 cells/mm³.
Hypersensitivity Reactions: Patients should be observed closely for hypersensitivity reactions, particularly during the first and second infusions. Hypersensitivity reactions may occur within a few minutes after initiation of a docetaxel infusion. If minor reactions (e.g., flushing or localized skin reactions) occur, interruption of therapy is not required. However, severe reactions (e.g., severe hypotension, bronchospasm or generalized rash/erythema) require immediate discontinuation of docetaxel and appropriate therapy. Patients who have developed severe hypersensitivity reactions should not be rechallenged with docetaxel.
Neurologic Effects: Severe neurosensory symptoms (e.g., paresthesia, dyesthesia, pain) were observed in metastatic breast cancer patients, and resulted in treatment discontinuation. When these symptoms occur, dosage must be adjusted. If symptoms persist, treatment should be discontinued. Patients who experienced neurotoxicity in clinical trials and for whom follow-up information on the complete resolution of the event was available had spontaneous reversal of symptoms with a median of 9 weeks from onset (range: 0 to 106 weeks). Severe peripheral motor neuropathy mainly manifested as distal extremity weakness were also reported.
Cutaneous Reactions: Localized skin erythema of the extremities (palms of the hands and soles of the feet) with edema followed by desquamation has been observed. Severe symptoms such as eruptions followed by desquamation which lead to interruption or discontinuation of docetaxel treatment were reported.
Asthenia: Severe asthenia has been reported in metastatic breast cancer patients and has led to treatment discontinuation. Symptoms of fatigue and weakness which may be associated with deterioration of performance status in patients with progressive disease may last for a few days up to several weeks.
Hepatic Impairment: Docetaxel therapy should not be given to patients with combined abnormalities of transaminases and alkaline phosphatase.
Respiratory Disorders: Acute respiratory distress syndrome, interstitial pneumonia/pneumonitis, interstitial lung disease, pulmonary fibrosis, and respiratory failure have been reported and may be associated with fatal outcome. Cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy.
If new or worsening pulmonary symptoms develop, patients should be closely monitored, promptly investigated, and appropriately treated. Interruption of docetaxel therapy is recommended until diagnosis is available. Early use of supportive care measures may help improve the condition. The benefit of resuming docetaxel treatment must be carefully evaluated.
Cardiovascular Disorder: Heart failure has been observed in patients receiving docetaxel in combination with trastuzumab, particularly following chemotherapy containing anthracycline (doxorubicin or epirubicin). This may be moderate to severe and has been associated with death.
Patients who are candidates for treatment with docetaxel in combination with trastuzumab should undergo baseline cardiac assessment. Cardiac function should be further monitored during treatment (e.g., every three months) to help identify patients who may develop cardiac dysfunction.
Symptoms of congestive heart failure (CHF) should be monitored in patients during therapy and follow-up period. The risk of CHF has been shown to be higher during the first year after treatment of node positive breast cancer in patients treated with TAC regimen.
Eye Disorder: Cystoids macular edema has been reported in patients treated with docetaxel. Patients with impaired vision should undergo a prompt and complete ophthalmologic examination. In case cystoids macular edema is diagnosed, docetaxel should be discontinued and appropriate treatment initiated.
Alcohol Content: The alcohol content in the dose of docetaxel injection may affect the central nervous system. Patients should be advised to avoid or minimize alcohol intake if they are taking docetaxel since there have been reports of cases of intoxication with some formulations of docetaxel.
Effects on ability to drive and use machines: Because of the alcohol content in a dose of docetaxel, this may impair a patient's ability to drive or use machines immediately after infusion.
Patients with Renal Impairment: Patients with bilirubin >ULN, AST and/or ALT >1.5 x ULN concomitant with alkaline phosphatase >2.5 x ULN should not receive docetaxel.
The alcohol content in docetaxel injection should be taken into account when given to patients with hepatic impairment.
Carcinogenicity, Mutagenicity, Impairment of Fertility: No studies have been conducted to fully assess docetaxel's long-term carcinogenic potential. However, based on its pharmacodynamic mechanism of action, docetaxel may be a carcinogen.
Docetaxel has been shown to be clastogenic in the in vitro chromosome aberration test in CHO-K₁ cells and in the in vivo micronucleus test in the mouse, but did not induce mutagenicity in the Ames test or the CHO/HPRT gene mutation assays.
In non-clinical studies, docetaxel has genotoxic effects and may alter male fertility. Thus, men being treated with docetaxel are advised not to father a child during and up to 6 months after treatment and to seek advice on conservation of sperm prior to treatment.
Use in Children: The safety and efficacy of docetaxel in children, one month to less than 18 years old, as monotherapy or in combination have not been established. The overall safety profile of docetaxel in children receiving monotherapy or TCF was consistent with the known safety profile in adults.
The alcohol content in docetaxel injection should be taken into account when given to pediatric patients.
Use in Elderly: Certain toxicities associated with docetaxel therapy may occur more frequently and with greater severity in the elderly patients particularly those with poor performance status, or otherwise non-life threatening indolent disease (such as relatively asymptomatic metastatic disease limited to the bone). Because of the greater frequency of decreased hepatic, renal, and/or cardiac function and of concomitant disease and the drug therapy observed in the elderly, caution is advised in dose selection for geriatric patients.