Date of approval.
Date of revision.
Docetaxel Injection Instructions
Please read the instructions carefully and use under the guidance of a physician
Drug Name]
Generic name: Docetaxel Injection
English name: Docetaxel Injection
Hanyu Pinyin：Duoxitasai Zhusheye
Ingredients
Active ingredient: Docetaxel
Chemical name: {2aR-[2aα,4β,4aβ,6β,9α,(αR*,βS*),11α,12α,12aα,12bα]}-β-{[(1,1-dimethylethoxy)carbonyl]amino}-α-carbonylbenzenepropanoic acid [12b-acetoxy-12-benzoyloxy-2a,3,4,4a,5,6,9,10,11,12, 12a,12b-Dodecahydro-4,6,11-trihydroxy-4a,8,13,13-tetramethyl-5-oxo-7,11-methylene-1H-cyclodecapentaeno[3,4]benzo[1,2-b]oxetan-9-yl] ester
Chemical structure formula.
Molecular formula: C43H53NO14
Molecular weight: 807.88
Excipients: Polysorbate 80, anhydrous citric acid and anhydrous ethanol.
Properties]: This product is a colorless to brownish yellow clear liquid.
Indications
Breast cancer
1.It is suitable for the treatment of locally advanced or metastatic breast cancer.
2.Docetaxel combined with trastuzumab is used for the treatment of metastatic breast cancer patients with HER 2 gene overexpression who have not received prior chemotherapy for metastatic cancer.
3. docetaxel in combination with adriamycin and cyclophosphamide for postoperative adjuvant chemotherapy in patients with lymph node positive breast cancer.
Non-small cell lung cancer
For the treatment of locally advanced or metastatic non-small cell lung cancer, even after failure of cisplatin-based chemotherapy.
Prostate cancer
Docetaxel in combination with prednisone or prednisolone is used to treat hormone-refractory metastatic prostate cancer.
Gastric cancer
Docetaxel in combination with cisplatin and 5-fluorouracil (TCF regimen) is used to treat advanced gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, that has not received prior chemotherapy.
Specification
1ml: 20mg
Dosage and Administration
Docetaxel should only be used for intravenous infusion.
Recommended dose.
General
The recommended dose of docetaxel is 75mg/m2 titrated over one hour every three weeks. To reduce the incidence and severity of fluid retention and to mitigate the severity of allergic reactions, all patients must be premedicated prior to receiving docetaxel therapy, except where contraindicated. Such medications may only include oral glucocorticoids, such as dexamethasone, taken one day prior to docetaxel titration at 16 mg per day (e.g., 8 mg twice daily) for 3 days. Only your doctor can modify the treatment regimen. Docetaxel should not be used in patients with a neutrophil count below 1500/mm3. During docetaxel treatment, the dose of docetaxel should be tapered as appropriate if the patient experiences febrile neutropenia; a neutrophil count below 500/mm3 for more than one week; severe or accumulating skin reactions or severe peripheral neurologic symptoms.
For the treatment of prostate cancer with concomitant administration of prednisone or prednisolone, the recommended pre-chemotherapy dose and regimen is: 12 hours, 3 hours and 1 hour prior to the patient’s treatment with docetaxel, oral dexamethasone 8 mg (see PRECAUTIONS). Prophylactic use of granulocyte colony-stimulating factor (G-CSF) to mitigate the risk of drug hematologic toxicity occurring.
Breast Cancer
In adjuvant chemotherapy for operable lymph node-positive breast cancer, the recommended dose is docetaxel 75 mg/m2 given every three weeks for six cycles after adriamycin 50 mg/m2 and cyclophosphamide 500 mg/m2 for one hour (see Adjusting Doses in Treatment).
The recommended dose for docetaxel administration in the treatment of patients with locally advanced or metastatic breast cancer is 100 mg/m2. for first-line dosing, docetaxel 75 mg/m2 in combination with adriamycin (50 mg/m2) (see Safe Disposition Recommendations).
In combination with trastuzumab, the recommended dose of docetaxel is 100 mg/m2 every three weeks and trastuzumab once weekly. In a pivotal clinical study, the first intravenous dose of docetaxel should be given one day after the first dose of trastuzumab. If the patient tolerated the previous trastuzumab dose well, subsequent doses of docetaxel should be administered immediately following the trastuzumab intravenous infusion. The dosage and administration of trastuzumab are described in its product insert.
Non-small cell lung cancer
For the treatment of non-small cell lung cancer, the recommended dose for previously untreated patients is docetaxel 75 mg/m2 and an immediate intravenous infusion of cisplatin 75 mg/m2 over 30-60 minutes. For patients who have failed prior platinum-containing therapy, the recommended dose of docetaxel is 75 mg/m2 as monotherapy.
Prostate cancer
The recommended dose is docetaxel 75mg/m2 every 3 weeks as a continuous course of oral prednisone or prednisolone 5mg twice daily
Gastric cancer
The recommended dose is docetaxel 60 mg/m2 infused over 1 hour, followed by cisplatin 60 mg/m2 infused over 1-3 hours (both on day 1 only), and 5-fluorouracil at the end of the cisplatin infusion at a dose of 600 mg/m2 daily for 24 hours IV for 5 days. Treatment was repeated every three weeks. Patients must be treated with antiemetics and moderately hydrated prior to cisplatin treatment. Recombinant granulocyte colony-stimulating factor (G-CSF) is recommended in the second and/or subsequent cycles in the event of febrile neutropenia or infection with neutropenia or neutropenia lasting more than 7 days (see Dose Adjustment in Therapy section). Patients are required to take oral dexamethasone as prophylaxis to avoid the development of allergic reactions and to reduce and/or delay the onset of skin toxicity and fluid retention associated with docetaxel. To be taken at the following prescribed times.
Dexamethasone 8 mg orally for 6 doses.
1. the night before chemotherapy
2. early in the morning immediately after waking up on the day of chemotherapy
3. 1 hour prior to docetaxel infusion
4. the evening of chemotherapy
5. the morning of the day after chemotherapy
6. the evening of the day after chemotherapy
Intra-treatment dose adjustment.
General.
Docetaxel should be used in patients with a neutrophil count ≥ 1500/mm3.
During docetaxel treatment, if the patient experiences febrile neutropenia; neutrophil count <500/mm3 for more than one week; severe or accumulating skin reactions or severe peripheral neurologic symptoms, the dose of docetaxel should be reduced from 100 mg/m2 to 75 mg/m2 and/or from 75 mg/m2 to 60 mg/m2. If the patient still has the above symptoms at the 60 mg/m2 If the patient continues to have these symptoms at the 60mg/m2 dose, treatment should be discontinued.
Adjuvant chemotherapy for breast cancer
In the pivotal clinical study, patients receiving adjuvant chemotherapy for breast cancer who developed concurrent neutropenia (including prolonged onset of neutropenia, febrile neutropenia, or infection) were recommended prophylaxis with G-CSF for all subsequent dosing cycles (e.g., days 4 through 11). If the patient continues to experience these reactions, G-CSF should be maintained and the docetaxel dose reduced to 60 mg/m2.
However, neutropenia may occur earlier in clinical practice. Therefore, the patient’s risk of neutropenia should be weighed against the currently used recommended dose and G-CSF should be used.
If G-CSF is not used, the docetaxel dose should be reduced to 60 mg/m2 from 75. Patients who develop grade 3 or 4 stomatitis should have the dose reduced to 60 mg/m2.
For trastuzumab dose adjustment when co-administered with trastuzumab, see its product insert.
Combination cisplatin therapy
For patients with a starting dose of docetaxel 75 mg/m2 in combination with cisplatin and who have had a platelet minimum <25,000/mm3 during the prior course, or have had febrile neutropenia, or have had severe non-hematologic toxicity, the docetaxel dose should be reduced to 65 mg/m2 for the next course. for cisplatin dose adjustment, see their product insert.
Combined cisplatin and 5-fluorouracil therapy.
For patients with advanced or recurrent gastric cancer at a starting dose of docetaxel 60 mg/m2 in combination with cisplatin and 5-fluorouracil (5-FU), dose adjustments may be made in the event of severe hematologic and/or non-hematologic toxicity during treatment. Toxic reactions were graded using NCI -CTC 3.0 criteria.
Some toxic reactions (e.g., diarrhea) may prompt a dose reduction of more than one drug in the combination.
If a patient experiences a toxic reaction and the recommended management regimen is conflicting, the most conservative dose adjustment recommended (the dose reduction appropriate for the most severe toxicity) should be used. Note: Dose reductions due to toxic reactions do not have to be re-increased.
Two consecutive drug reductions may be made when a toxic reaction occurs; if two dose reductions and/or up to 2 weeks of delayed dosing do not alleviate this toxic reaction, treatment should be discontinued.
Hematologic toxicity.
If febrile neutropenia, prolonged duration of neutropenia, or neutropenic infections occur despite the use of G-CSF, the docetaxel dose should be reduced by 20%. If concurrent neutropenia reappears, the docetaxel dose should be reduced again by 20%. If platelets are reduced to <50 x 109/L, the docetaxel dose should be reduced by 20%. The next course of therapy should be administered only when the neutrophil count has recovered to ≥1.5 × 109/L and the platelet count has recovered to ≥75 × 109/L, with dose adjustment according to the most serious adverse event that occurred during the previous cycle.
Gastrointestinal toxicity.
Toxic Dose Adjustment Diarrhea Grade 3 First occurrence: 20% reduction in 5-FU dose
Second occurrence: docetaxel dose reduction by 20%
Third occurrence: discontinuation of treatment Diarrhea Grade 4 First occurrence: 20% reduction in both docetaxel and 5-FU dose
Second occurrence: discontinuation of treatment Stomatitis Grade 3 first occurrence and lasting more than 48 hours: 20% reduction in 5-FU dose
second occurrence: discontinuation of 5-FU in subsequent courses
Third occurrence: docetaxel dose reduction by 20%. Stomatitis Grade 4 First presentation: discontinue 5-FU for subsequent courses.
Second occurrence: docetaxel dose reduced by 20%. Skin reactions: If Grade 3 skin reactions occur during the course of treatment, delay dosing to ≤ Grade 1 and reduce docetaxel dose by 20% before retreatment.
Nail changes: No dose adjustment.
Special Populations
Patients with impaired hepatic function: Based on pharmacokinetic data from 100 mg/m2 docetaxel monotherapy, the recommended dose of docetaxel is 75 mg/m2 for patients with ALT and/or AST>1.5 x ULN along with alkaline phosphatase>2.5 x ULN (see Precautions and Pharmacokinetics). For patients with serum bilirubin >ULN and/or ALT and AST >3.5×ULN with concomitant alkaline phosphatase >6×ULN, it should not be used unless strictly indicated, and no dose reduction is recommended.
Docetaxel in combination with cisplatin and 5-FU for the treatment of gastric cancer did not include patients with ALT and/or AST>1.5×ULN along with alkaline phosphatase>2.5×ULN, and bilirubin>ULN in the pivotal clinical study. It should not be used in such patients unless there is a strict indication for its use, and there is no recommendation for dose reduction. There are also no data on docetaxel combination therapy in patients with impaired hepatic function in other indications.
[Adverse Reactions].
Adverse reactions likely or possibly associated with docetaxel were collected from the following patients on monotherapy and in combination.
. 1312 patients received 100 mg/m2 and 121 patients received 75 mg/m2 docetaxel monotherapy.
. 258 patients received 75 mg/m2 docetaxel in combination with adriamycin 50 mg/m2.
. 406 patients received 75 mg/m2 docetaxel in combination with cisplatin 75 mg/m2.
. 92 patients were treated with docetaxel in combination with trastuzumab.
. 332 patients received docetaxel in combination with prednisone or prednisolone.
. 1,276 patients (744 in the TAX316 trial and 532 in the GEICAM9805 trial) received docetaxel in combination with adriamycin and cyclophosphamide.
. 300 patients with gastric cancer (221 subjects in phase III clinical trials and 79 subjects in phase II clinical trials) received docetaxel in combination with cisplatin and 5-FU.
The types and severity of reactions were mainly described according to the NCI generic toxicity criteria (Grade 3 = G3, Grades 3-4 = G3/4; Grade 4 = G4) and the COSTART and MedDRA terms. Severity” in some tables follows the descriptions in the original data from earlier completed clinical studies and is based on the subjective judgment of the investigator and is defined as a Grade 3 and/or Grade 3-4 adverse event. Frequencies were defined as: very common (≥1/10), common (≥1/100, 1/10); uncommon (≥1/1000, 1/100); rare (≥1/10,000, <1/1000); and very rare (<1/10,000).
Adverse reactions are listed in each frequency group in order of severity from highest to lowest.
The most commonly reported adverse reactions to docetaxel monotherapy were: neutropenia [reversible and non-accumulative see Dosage and Administration and Precautions; median duration of reduction to nadir was 7 days, median duration of severe neutropenia (<500/mm3) occurred for 7 days], anemia, alopecia, nausea, vomiting, stomatitis, diarrhea, and weakness. The severity of docetaxel adverse events can be increased when docetaxel is used in combination with other chemotherapeutic agents.
Adverse events with an incidence of ≥10% (all grades) reported in combination trastuzumab therapy are listed. The incidence of SAEs (40% versus 31%) and grade 4 AEs (34% versus 23%) was increased in the trastuzumab combination arm compared to the docetaxel monotherapy arm.
Common adverse reactions to docetaxel were as follows.
Immune system disorders
Most allergic reactions occur within the first few minutes of starting docetaxel infusion and are usually mild to moderate. The most commonly reported symptoms are: facial flushing, rash with or without pruritus, chest tightness, back pain, dyspnea and fever or chills. Severe reactions include, hypotension and/or bronchospasm or a generalized rash/erythema that recovers with discontinuation of the infusion and symptomatic treatment (see PRECAUTIONS).
Various neurological disorders
The dose of docetaxel should be reduced when symptoms of severe peripheral neurotoxicity are present (see DOSAGE AND ADMINISTRATION and PRECAUTIONS). Mild to moderate sensory neurological symptoms include abnormal sensation, sensory disturbances or pain including burning pain. Motor nerve events manifest primarily as weakness.
Skin and subcutaneous tissue disorders
A usually mild to moderate reversible skin reaction is observed, often manifesting as a rash, including a localized rash that occurs primarily on the hands and feet (including severe hand-foot syndrome), or on the arms, face and chest, often with pruritus. The rash most often occurs within one week of docetaxel infusion. Rarely, severe symptoms such as a rash followed by peeling that interferes with or interrupts docetaxel therapy have been reported (see DOSAGE AND ADMINISTRATION and PRECAUTIONS). Severe nail lesions, characterized by hyperpigmentation or hypopigmentation, sometimes with pain and nail loss. In some cases, multiple factors may have contributed to these findings, such as the patient’s concomitant infection, concomitant other medications, and underlying disease.
Systemic disease and various reactions at the site of administration
Injection site reactions are generally mild and include hyperpigmentation, inflammation, redness or dryness of the skin, phlebitis or exudation, and swelling.
Fluid retention includes, for example, peripheral edema and, in rare cases, pleural effusion, pericardial effusion, ascites and weight gain. Peripheral edema usually begins in the lower extremities and may progress to the whole body with weight gain of 3 kg or more. The incidence and extent of fluid retention is accumulative (see PRECAUTIONS).
Docetaxel 100 mg/m2 as a single agent.
MedDRA System
Organ classification Very common adverse reactions Common adverse reactions Uncommon adverse reactions Infections and invasive diseases Infections (G3/4: 5.7%, including sepsis and pneumonia, 1.7% lethal) Infections combined with grade IV neutropenia (G3/4: 4.6%) Hematologic and lymphatic system disorders Neutropenia (G4: 76.4%); anemia (G3/4:8.9%) Febrile neutropenic thrombocytopenia (G4: 0.2%) Immune system disorders Hypersensitivity reactions (G3/4: 5.3%) Metabolic and nutritional disorders Anorexia Various neurological disorders Peripheral sensory neuropathy (G3:4.1%)
Peripheral motor neuron disease (G3/4: 4%)
Taste abnormalities (severe 0.07%) Diseases of cardiac organs Arrhythmia (G3/4: 0.7%) Heart failure Vascular and lymphovascular diseases Hypotension.
Hypertension.
Hemorrhage Respiratory, thoracic and mediastinal diseases dyspnea (severe 2.7%) Gastrointestinal system diseases stomatitis (G3/4: 5.3%)
Diarrhea (G3/4: 4%).
Nausea (G3/4: 4%)
Vomiting (G3/4: 3%) Constipation (severe 0.2%)
Abdominal pain (severe 1%).
Gastrointestinal bleeding (0.3% severe) Esophagitis (0.4% severe) Skin and subcutaneous tissue disorders Hair loss
Skin reactions (G3/4: 5.9%)
Nail changes (severe 2.6%). Various musculoskeletal and connective tissue disorders Myalgia (severe 1.4%) Arthralgia Systemic disorders and various reactions at the site of administration Fluid retention (severe: 6.5%)
Weakness (severe 11.2%).
Painful injection site reactions.
Non-cardiogenic chest pain (severe 0.4%) Various tests G3/4 Elevated blood bilirubin
(<5%).
G3/4 elevated blood alkaline phosphatase (<4%).
G3/4 elevated AST (<3%)
G3/4 ALT elevation (<2%) Hematologic and lymphatic system disorders
Rare: bleeding events combined with G3/4 thrombocytopenia
Various neurological disorders
Data suggest that 35.3% of patients with neurotoxic reactions are reversible after docetaxel 100 mg/m2 monotherapy. It recovered spontaneously within 3 months.
Skin and subcutaneous tissue disorders
Very rare: one case of alopecia, not reversed at the end of the study. 73% of skin reactions were reversed within 21 days.
Systemic disease and various reactions at the dosing site
The median cumulative dose to treatment interruption was over 1,000 mg/m2 and the median time to recovery of fluid retention was 16.4 weeks (range 0-42 weeks). The onset of moderate and severe fluid retention was delayed in patients on prophylaxis (median cumulative dose: 818.9 mg/m2) compared to patients not on prophylaxis (median cumulative dose: 489.7 mg/m2); however, fluid retention was reported to occur early in treatment in some patients.
Docetaxel 75 mg/m2 as a single agent.
MedDRA Systematic Organ Classification Very Common Adverse Reactions Common Adverse Reactions Infections and Infectious Diseases Infections (G3/4:5%). Hematologic and Lymphatic System Disorders Neutropenia (G4:54.2%).
Anemia (G3/4:10.8%).
Thrombocytopenia (G4:1.7%). Febrile neutropenia Immune system disorders Hypersensitivity reactions (no severe events) Metabolic and nutritional disorders Anorexia Various neurological disorders Peripheral sensory neuropathy (G3:0.8%) Peripheral motor neuron disease (G3:2.5%) Cardiac organ disorders Arrhythmias (no severe events); Vascular and lymphovascular disorders Hypotension Gastrointestinal system disorders Nausea (G3/4:3.3%)
Stomatitis (G3/4:1.7%)
Vomiting (G3/4:0.8%)
diarrhea (G3/4:1.7%) constipation skin and subcutaneous tissue disorders hair loss; skin reactions (G3/4: 0.8%) nail changes (severe 0.8%) various musculoskeletal and connective tissue disorders myalgia systemic disorders and various reactions at the site of administration weakness (severe 12.4%)
Fluid retention (0.8% severe)
Pain Various tests Elevated G3/4 blood bilirubin (<2%) Docetaxel 75 mg/m2 in combination with Adriamycin.
MedDRA system
Organ classification Very common adverse reactions Common adverse reactions Uncommon adverse reactions Infections and invasive diseases Infections (G3/4:7.8%) Hematologic and lymphatic system disorders Neutropenia (G4:91.7%)
Anaemia (G3/4:9.4%).
Febrile neutropenia.
Thrombocytopenia (G4:0.8%) Immune system disorders Hypersensitivity reactions (G3/4: 1.2%) Metabolic and nutritional disorders Anorexia Various neurological disorders Peripheral sensory neuropathy (G3:0.4%) Peripheral motor neuron disease (G3:0.4%) Cardiac organ disorders Heart failure.
Arrhythmias (no severe events) Vascular and lymphovascular diseases Hypotension Gastrointestinal system diseases Nausea (G3/4:5%)
Stomatitis (G3/4:7.8%).
Diarrhea (G3/4:6.2%)
Vomiting (G3/4:5%).
Constipation Hair loss in skin and subcutaneous tissue disorders.
Nail changes (0.4% severe).
Skin reactions (no severe events) Various musculoskeletal and connective tissue disorders Myalgia Systemic disorders and various reactions at the site of administration Weakness (severe 8.1%)
Fluid retention (1.2% severe)
Painful injection site reactions Various tests Elevated G3/4 blood bilirubin (<2.5%).
G3/4 elevated blood alkaline phosphatase (<2.5%) G3/4 elevated AST (<1%).
G3/4 ALT elevation (<1%) Docetaxel 75 mg/m2 in combination with cisplatin.
MedDRA system
Organ Classification Very common adverse reactions Common adverse reactions Uncommon adverse reactions Infection and invasive disease Infection (G3/4:5.7%) Hematologic and lymphatic system disorders neutropenia (G4:51.5%).
Anemia (G3/4:6.9%).
Thrombocytopenia (G4:0.5%); febrile neutropenia Immune system disorders Hypersensitivity reactions (G3/4: 2.5%) Metabolic and nutritional disorders Anorexia Various neurological disorders Peripheral sensory neuropathies (G3:3.7%)
Peripheral motor neuron disease (G3/4:2%) Diseases of cardiac organs Arrhythmia (G3/4:0.7%) Heart failure Vascular and lymphovascular diseases Hypotension (G3/4:0.7%) Diseases of the gastrointestinal system Nausea (G3/4:9.6%)
Vomiting (G3/4:7.6%)
Diarrhea (G3/4:6.4%)
Stomatitis (G3/4:2%) Constipation Skin and subcutaneous tissue disorders Hair loss
Nail changes (severe 0.7%)
Skin reactions (G3/4: 0.2%) Various musculoskeletal and connective tissue disorders Myalgia (severe 0.5%) Systemic disorders and various reactions to weakness at the site of administration (severe 9.9%)
Fluid retention (0.7% severe)
Fever (G3/4:1.2%) Injection site reactions.
Pain Various tests Elevated G3/4 blood bilirubin (2.1%).
G3/4 ALT elevation (1.3%) G3/4 AST elevation (0.5%)
G3/4 elevated blood alkaline phosphatase (0.3%) Docetaxel 100 mg/m2 in combination with trastuzumab.
MedDRA system
Organ classification Very common adverse reactions Common adverse reactions Blood and lymphatic system disorders Neutropenia (G3/4:32%).
Febrile neutropenia (including neutropenia with fever and antibiotics) or neutropenic sepsis Metabolic and nutritional disorders Anorexia Mental abnormalities Insomnia Various neurological disorders Sensory abnormalities; headache; taste abnormalities; hyposensitivity; Eye organ abnormalities Increased tearing; conjunctivitis Heart organ disorders Heart failure Vascular and lymphatic vessel disorders Lymphedema Respiratory, thoracic and mediastinal Diseases epistaxis; sore throat; nasopharyngitis; dyspnea; cough; nasal overflow Gastrointestinal system diseases nausea; diarrhea; vomiting; constipation; stomatitis; dyspepsia; abdominal pain Skin and subcutaneous tissue diseases alopecia; erythema; rash; nail changes Various musculoskeletal and connective tissue diseases myalgia; arthralgia; limb pain; bone pain; back pain Systemic diseases and various reactions at the site of administration weakness; peripheral edema; fever Fatigue; mucositis; pain; flu-like illness; chest pain; chills Weight gain on various tests Blood and lymphatic system disorders
Very common: Increased hematologic toxicity compared to docetaxel monotherapy in patients receiving docetaxel in combination with trastuzumab (G3/4 neutropenia using NCI-CTC criteria, 32% versus 22%). It is important to note that this response may have been underestimated, as tests of the lowest complete blood count at 100 mg/m2 of docetaxel alone showed that neutropenia occurred in 97% of patients, 76% of whom were grade 4. The incidence of febrile neutropenia/neutropenic sepsis was higher than in patients in the docetaxel combined with trastuzumab treatment group (23% versus 17%) compared to docetaxel alone.
Cardiac organ disease
Symptomatic heart failure was reported in 2.2% of patients in the group receiving docetaxel in combination with trastuzumab compared with 0% in the docetaxel monotherapy group. In the group receiving docetaxel in combination with trastuzumab, 64% received prior anthracycline adjuvant therapy compared to 55% in the docetaxel monotherapy group.
Docetaxel 75 mg/m2 in combination with prednisone or prednisolone.
MedDRA System Organ Classification Very Common Adverse Reactions Common Adverse Reactions Infections and Infectious Diseases Infections (G3/4: 3.3%) Hematologic and Lymphatic System Disorders Neutropenia (G3/4: 32%).
Anemia (G3/4: 4.9%) Thrombocytopenia (G3/4: 0.6%)
Febrile neutropenia Immune system disorders Hypersensitivity reactions (G3/4: 0.6%) Metabolic and nutritional disorders Anorexia (G3/4: 0.6%) Various neurological disorders Peripheral sensory neuropathies (G3/4: 1.2%)
Taste abnormalities (G3/4: 0%) Peripheral motor neuron disease (G3/4: 0%) Ocular organ abnormalities Increased tearing (G3/4: 0.6%) Cardiac organ diseases Left ventricular hypoperfusion (G3/4: 0.3%) Respiratory, thoracic and mediastinal diseases Epistaxis (G3/4: 0%)
Dyspnea (G3/4: 0.6%)
Cough (G3/4: 0%) Gastrointestinal disorders nausea (G3/4: 2.4%)
Diarrhea (G3/4: 1.2%).
Stomatitis/pharyngitis (G3/4: 0.9%)
Vomiting (G3/4: 1.2%) Hair loss in skin and subcutaneous tissue type disorders.
Nail changes (no severe events) Exfoliative rash (G3/4: 0.3%) Various musculoskeletal and connective tissue disorders Arthralgia (G3/4: 0.3%)
Myalgia (G3/4: 0.3%) Systemic diseases and various reactions to fatigue at the site of administration (G3/4: 3.9%)
Fluid retention (severe: 0.6%) The following relevant data were obtained from the Chinese Prostate Cancer Registry Study, which showed similar results to the above table, and no new adverse reactions were identified.
MedDRA Systematic Organ Classification Very Common Adverse Reactions Common Adverse Reactions Infections and Infectious Diseases Pulmonary Infections (G3/4: 1.8%)
Infection (G3/4: 0.9%) Blood and lymphatic system abnormalities Febrile neutropenia
(G3/4: 1.8%) Reduced neutrophil count in all types of examinations (G3/4: 57.66%)
Decreased white blood cell count (G3/4: 17.12%) decreased hemoglobin (G3/4: 3.6%); gastrointestinal disorders oral ulcers (G3/4: 0.9%).
Pharyngitis (G3/4: 0.9%)
Nausea
Diarrhea (G3/4: 1.8%); skin and subcutaneous tissue abnormalities Hair loss (G3/4: 3.6%); systemic and injection site abnormalities Fatigue
Fever (G3/4: 4.5%) List of adverse reactions to docetaxel 75 mg/m2 in combination with adriamycin and cyclophosphamide in lymph node positive (TAX-316) and lymph node negative (GEICAM9805) breast cancer patients with integrated data.
MedDRA System
Organ classification Very common adverse reactions Common adverse reactions Uncommon adverse reactions Infections and infectious-like disease infections (G3/4: 2.4%).
Neutropenic infections (G3/4: 2.6%). Anemia of the blood and lymphatic system (G3/4: 3%).
Neutropenia (G3/4: 59.2%).
Thrombocytopenia (G3/4: 1.6%).
Febrile neutropenia (G3/4: NA) Immune system disorders Hypersensitivity reactions (G3/4: 0.6%) Metabolic and nutritional disorders Anorexia (G3/4: 1.5%) Various neurological disorders Abnormal taste perception (G3/4: 0.6%)
Peripheral sensory neuropathy (G3/4: <0.1%) Peripheral motor neuron disease (G3/4: 0%); syncope (G3/4: 0%)
Neurotoxicity (G3/4: 0%)
Drowsiness (G3/4: 0%) Ocular organ abnormalities Conjunctivitis (G3/4: <0.1%) Increased tearing (G3/4<0.1%) Cardiac organ disease Arrhythmia (G3/4: 0.2%) Vascular and lymphatic vessel diseases Hot flashes (G3/4: 0.5%) Hypotension (G3/4: 0%)
Phlebitis (G3/4: 0%) Lymphedema (G3/4: 0%) Respiratory, thoracic and mediastinal disorders Cough (G3/4: 0%) Gastrointestinal disorders Nausea (G3/4: 5.0%)
Stomatitis (G3/4: 6.0%)
Vomiting (G3/4: 4.2%)
Diarrhea (G3/4: 3.4%).
Constipation (G3/4: 0.5%) Abdominal pain (G3/4: 0.4%) Skin and subcutaneous tissue disorders Hair loss (persistent<3%)
Skin lesions (G3/4: 0.6%)
Nail changes (G3/4: 0.4%) Myalgia in various musculoskeletal and connective tissue disorders (G3/4: 0.7%)
Arthralgia (G3/4: 0.2%) Reproductive system and breast diseases amenorrhea (G3/4: NA) Systemic diseases and various reactions to weakness at the site of administration (G3/4: 10.0%)
Fever (G3/4: NA).
Peripheral edema (G3/4: 0.2%) Various examinations Increase in body weight (G3/4: 0%)
Weight loss (G3/4: 0.2%) Various neurological disorders
In the lymph node-positive breast cancer study (TAX316) persistent peripheral sensory neuropathy was observed at the end of chemotherapy in 10 of 84 patients who had peripheral sensory neuropathy during follow-up.
Cardiac organ disease
In the TAX316 study, 26 (3.5%) patients in the TAC group and 17 (2.3%) patients with FAC, developed congestive heart failure. All of the above patients were diagnosed with congestive heart failure after 30 days of the treatment period, except for one patient in each treatment group. 2 patients in the TAC group and 4 patients in the FAC group died of heart failure.
In the GEICAM 9805 study, 3 (0.6%) patients in the TAC group and 3 (0.6%) patients in the FAC group developed congestive heart failure during the follow-up period. 1 patient in the TAC group died of dilated cardiomyopathy
Skin and subcutaneous tissue-based diseases
In the TAX316 study, 687 patients in the TAC group and 645 patients in the FAC group reported alopecia during the follow-up period after the end of chemotherapy.
Persistent alopecia was observed in 29 patients in the TAC group (3.9%) and 16 patients in the FAC group (2.2%) at the end of the follow-up period.
In the GEICAM9805 study, 49 patients (9.2%) in the TAC group and 35 patients (6.7%) in the FAC group reported continued alopecia during the follow-up period after the end of chemotherapy. Persistent alopecia was observed in 3 (0.6%) patients in the TAC group and 1 (0.2%) patient in the FAC group at the end of the follow-up period.
Reproductive system and breast disease
In the TAX316 study, ongoing amenorrhea was observed at the end of chemotherapy in 121 of the 202 patients with amenorrhea at the end of follow-up.
In the GEICAM9805 study, persistent amenorrhea was observed in 18 (3.4%) patients in the TAC group and 5 (1.0%) patients in the FAC group at a median follow-up of 10 years and 5 months.
Systemic disease and various reactions at the site of administration
In the TAX316 study, at the end of chemotherapy, persistent peripheral edema was observed during follow-up in 19 of 119 patients in the TAC group who had peripheral edema, and in 4 of 23 patients in the FAC group.
In the GEICAM 9805 study, lymphedema was observed to persist at the end of chemotherapy in 4 of the 5 patients in the TAC group who had lymphedema and during follow-up, and in 1 of the 2 patients in the FAC group who had lymphedema during follow-up.
Acute leukemia/myelodysplastic syndrome
During the 10-year follow-up of the TAX316 study, 4 of 744 patients in the TAC group and 1 of 736 patients in the FAC group were reported to have acute leukemia. 2 of 744 patients in the TAC group and 1 of 736 patients in the FAC group were reported to have myelodysplastic syndromes.
During the 10-year follow-up of the GEICAM 9805 study, acute leukemia was reported in 1 of 532 patients (0.2%) in the TAC group and no cases were reported in patients in the FAC group. No patient was diagnosed with myelodysplastic syndrome in either of the two on-treatment groups.
Complications of neutropenia
The table below shows that the incidence of grade 4 neutropenia, febrile neutropenia and neutropenic infections was reduced in patients receiving G-CSF primary prophylaxis in the GEICAM9805 study TAC group.
The incidence of complications of neutropenia in patients in the TAC group who received or did not receive G-CSF primary prophylaxis (GEICAM 9805).
Did not receive G-CSF primary prophylaxis
(n = 111)
n (%) Received G-CSF primary prophylaxis
(n = 421)
n (%) Neutropenia (G 4) 104 (93.7) 135 (32.1) Febrile neutropenia 28 (25.2) 23 (5.5) Neutropenic infection 14 (12.6) 21 (5.0) Neutropenic infection (G3/4) 2 (1.8) 5 (1.2) Docetaxel 75 mg/m2 combined with cisplatin and 5 Fluorouracil for gastric adenocarcinoma (according to the V325 study) List of adverse reactions.
MedDRA Systematic Organ Classification Very Common Adverse Reactions Common Adverse Reactions Infections and Infectious Diseases Neutropenic infections.
Infections (G3/4: 11.7%) Blood and lymphatic system disorders Anemia (G3/4: 20.9%)
Neutropenia (G3/4: 83.2%)
Thrombocytopenia (G3/4: 8.8%)
febrile neutropenia immune system disorders hypersensitivity reactions (G3/4: 1.7%) metabolic and nutritional disorders anorexia (G3/4: 11.7%) various neurological disorders peripheral sensory neuropathy (G3/4: 8.7%) dizziness (G3/4: 2.3%)
Peripheral motor neuron disease (G3/4: 1.3%) Eye organ abnormalities Increased tearing (G3/4: 0%) Ear and vagus type disorders Hearing impairment (G3/4: 0%) Heart organ disorders Arrhythmia (G3/4: 1.0%) Gastrointestinal system disorders Diarrhea (G3/4: 19.7%)
Nausea (G3/4: 16.0%)
Stomatitis (G3/4: 23.7%)
Vomiting (G3/4: 14.3%) Constipation (G3/4: 1.0%)
Gastrointestinal pain (G3/4: 1.0%)
esophagitis/difficulty swallowing/painful swallowing (G3/4: 0.7%) skin and subcutaneous tissue disorders hair loss (G3/4: 4.0%) rash/pruritus (G3/4: 0.7%)
Nail changes (G3/4: 0.7%)
Peeling (G3/4: 0%) Systemic disease and various reactions to drowsiness at the site of administration (G3/4: 19.0%)
Fever (G3/4: 2.3%).
Fluid retention (severe/life-threatening: 1.0%) Hematologic and lymphatic system abnormalities
The incidence of febrile neutropenia and neutropenic infections was 17.2% and 13.5%, respectively, and was not associated with the use of G-CSF. 19.3% of patients (10.7% of cycles) used G-CSF as a secondary prophylactic agent. The incidence of febrile neutropenia and neutropenic infections was 12.1% and 3.4%, respectively, when patients were on G-CSF prophylactically, compared with 15.6% and 12.9%, respectively, when G-CSF was not used.
List of adverse reactions to docetaxel 60 mg/m2 combined with cisplatin and 5-fluorouracil for advanced gastric adenocarcinoma (according to the Chinese DOCET_L_02195 study).
MedDRA system
Organ Classification Very common adverse reactions Common adverse reactions Uncommon adverse reactions Infectious and invasive diseases Infection (G3/4: 0.8%) Infectious small bowel colitis (G3/4: 0.8%).
Septic shock (G3/4: 0.8%) Blood and lymphatic system disorders Anemia (G3/4: 5.0%)
Febrile neutropenia (G3/4: 12.6%) Leukopenia (G3/4: 0.8%) Immune system abnormalities Hypersensitivity reactions (G3/4: 0.8%) Metabolic and nutritional abnormalities Decreased appetite (G3/4: 2.5%) Hyponatremia (G3/4: 3.4%)
Hypocalcemia (G3/4: 0.8%)
Hypokalemia (G3/4: 1.7%)
Hypomagnesemia; hypoproteinemia Mental abnormalities Cognitive impairment; delirium
(G3/4: 0.8%) Various neurological disorders Dizziness; hyperalgesia Peripheral sensory neuropathy (G3/4: 0.8%)
Syncope (G3/4: 0.8%)
Headache; palmoplantar redness and pain syndrome Ear and vagus type disorders Hearing loss (G3/4: 0.8%) Heart organ disorders Palpitations Gastrointestinal system disorders Diarrhea (G3/4: 12.6%)
Nausea (G3/4: 2.5%)
Stomatitis (G3/4: 4.2%)
Mouth ulcers (G3/4: 3.4%)
Vomiting (G3/4: 7.6%) Constipation.
Abdominal pain (G3/4: 0.8%)
Intestinal obstruction
(G3/4: 1.7%); eructation; dyspepsia; abdominal distention; dry mouth; vomiting blood; esophagitis abdominal discomfort; anal abscess; colitis; taste disturbance; black stool; oral mucosal erythema hepatobiliary system disorders hyperbilirubinemia liver injury.
Abnormal liver function renal disease and urinary system disease renal damage vascular and lymphatic disorders hypotension various musculoskeletal and connective tissue disorders arthralgia back pain; myalgia; limb pain skin and subcutaneous tissue disorders alopecia (G3/4: 3.4%) rash; subcutaneous hemorrhage; nail pigmentation systemic disorders and various reactions at the site of administration weakness (G3/4: 1.7%); fever (G3/ 4: 0.8%).
Fatigue; chest discomfort; discomfort; peripheral edema facial flushing; pain respiratory, thoracic and mediastinal disorders oropharyngeal pain tonsillitis genital and breast disorders irregular menstruation various types of examinations decreased white blood cell count (G3/4: 52.1%)
Reduced neutrophil count
(G3/4: 60.5%).
Decreased hemoglobin (G3/4: 3.4%)
Decreased platelet count
(G3/4: 1.7%).
Decreased lymphocyte count
(G3/4: 10.1%).
Decreased red blood cell count.
Elevated alanine aminotransferase
(G3/4: 0.8%).
elevated aspartate aminotransferase (G3/4: 1.7%) elevated blood bilirubin.
Elevated blood alkaline phosphatase.
Decreased renal creatinine clearance.
Elevated blood glucose.
Elevated white blood cell count (G3/4: 0.8%).
decreased monocyte count (G3/4: 0.8%) elevated blood myohepatitis.
Decreased blood magnesium.
Decreased blood albumin.
Elevated blood urea.
Reduced total protein post-marketing experience
Benign and malignant tumors (including cysts and polyps)
Very rare docetaxel-related acute myelogenous leukemia and myelodysplastic syndrome when combined with other chemotherapeutic agents and/or radiotherapy.
Hematologic and lymphatic system disorders
Bone marrow suppression and other hematologic adverse reactions have been reported. Disseminated intravascular coagulation (DIC) often associated with sepsis or multi-organ failure has been reported.
Immune system disorders
Cases of anaphylaxis have been reported rarely, and very rarely with fatal outcome in patients who have been treated with pre-chemotherapy agents.
Various neurological disorders
Cases of convulsions or temporary loss of consciousness following docetaxel treatment are rare. This reaction sometimes occurs during drug infusion.
Eye organ abnormalities
Transient visual disturbances (flickering, flashing lights, blind spots) have been reported rarely, especially during intravenous infusion of the drug, and are associated with allergic reactions. It may be reversed after discontinuation of the infusion. Tearing with or without conjunctivitis has been reported rarely, especially in patients receiving other anticancer drugs concomitantly, and tearing due to lacrimal duct obstruction has been reported very rarely.
As with other paclitaxel drugs, cystic macular edema has been reported after docetaxel treatment.
Ear and vagus disorders
Rare reports of ototoxicity, hearing impairment, and/or hearing loss have been reported, including cases caused by other ototoxic drugs.
Cardiac organ disease
Myocardial infarction has been reported rarely.
Vascular and Lymphatic Vessel Disease
Rare reports of venous embolism.
Respiratory, thoracic and mediastinal diseases
Acute respiratory distress syndrome, interstitial pneumonia, interstitial lung disease, pulmonary fibrosis and respiratory failure have been reported rarely. Radiation pneumonia has been reported rarely in patients with combined radiotherapy.
Gastrointestinal disorders
Gastrointestinal events such as gastrointestinal perforation, ischemic enterocolitis, colitis and neutropenic small bowel colitis are rare. Rarely, intestinal obstruction and bowel obstruction have been reported.
Hepatobiliary system abnormalities
Very rare reports of hepatitis, sometimes fatal in patients with pre-existing liver disorders.
Skin and subcutaneous tissue disorders
Very rare reports of docetaxel-associated cutaneous lupus erythematosus and maculopapular rashes such as erythema multiforme or Stevens-Johnson syndrome, toxic epidermal necrolysis and scleroderma-like changes. In some cases concomitant factors may contribute to the development of such events. In some cases, other combined factors such as concomitant infections, concomitant medications and underlying diseases may also play a role in the development of these abnormalities.
Systemic disease and various reactions at the site of administration
Rarely reported recall reactions to radiation therapy
Fluid retention not accompanied by acute oliguria or hypotension. The occurrence of dehydration and pulmonary edema has been reported rarely.
Renal and urinary system adverse reactions
Renal insufficiency and renal failure have been reported, and most cases of these adverse reactions occurred with concomitant receipt of other nephrotoxic drugs.
Metabolic and nutritional disorders
Hyponatremia has been reported and is often associated with dehydration, vomiting and pneumonia.
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Docetaxel should not be used in patients with a baseline neutrophil count <1500/mm3.
Docetaxel is not permitted for use in women who are pregnant.
Due to the unavailability of relevant data, docetaxel should not be used in patients with severe impairment of hepatic function (see PRECAUTIONS and DOSAGE and ADMINISTRATION).
When other drugs are used in combination with docetaxel, the contraindications of the other drugs should be followed.
[Precautions].
Docetaxel must be used under the guidance of a physician experienced in the application of cancer chemotherapy drugs. Due to the possibility of more serious allergic reactions, appropriate emergency facilities should be available and close monitoring of major functional indicators is recommended during injection.
For the treatment of breast cancer and non-small cell lung cancer, unless contraindicated, prophylaxis is required prior to docetaxel treatment to reduce the incidence and severity of fluid retention and the severity of allergic reactions, including oral corticosteroids such as dexamethasone 16 mg daily (8 mg BID), started one day before docetaxel injection for 3 days (see Dosage and Administration). .
For the treatment of prostate cancer, patients receive oral dexamethasone 8 mg 12 hours, 3 hours and 1 hour prior to docetaxel treatment (see Dosage and Administration).
Hematology
Neutropenia is the most common adverse effect of docetaxel treatment. The median time to nadir neutropenia is 7 days, but this interval may be shortened in patients on multiple treatments. A complete blood count should be monitored frequently in all docetaxel-treated patients. Patients should receive docetaxel only when their neutrophil count has recovered to ≥1500/mm3 or higher (see Dosage and Administration).
If severe neutropenia (<500/mm3 for 7 days or more) occurs during docetaxel treatment, dose reduction or appropriate symptomatic management is recommended for the next course of therapy (see DOSAGE AND ADMINISTRATION).
Patients treated with docetaxel in combination with cisplatin and 5-FU (TCF) should be closely monitored for reduced odds of febrile neutropenia and neutropenic infections when prophylaxis is given with G-CSF. And, patients treated with TCF should be given G-CSF prophylactically to reduce the risk of developing concurrent neutropenia (febrile neutropenia, prolonged neutropenia, or neutropenic infection). (See DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS).
Patients receiving docetaxel in combination with adriamycin and cyclophosphamide (TAC) should be closely monitored for a reduced incidence of febrile neutropenia and neutropenic infections when G-CSF is given as primary prevention. Also, patients receiving adjuvant therapy with TAC should be considered for primary prevention with G-CSF to reduce the risk of concurrent neutropenia (febrile neutropenia, prolonged neutropenia, or neutropenic infections). (See Dosage and Administration and Adverse Reactions).
Allergic Reactions
Patients should be closely monitored for allergic reactions, especially during the 1st and 2nd infusions. Anaphylactic reactions are possible within the first few minutes of starting docetaxel infusion; therefore, equipment should be available to treat hypotension and bronchospasm. Severe allergic reactions such as generalized rash/erythema, severe hypotension, bronchospasm or rare fatal anaphylactic reactions have been reported in patients who have received pre-chemotherapy dosing. The occurrence of anaphylactic reactions requires immediate discontinuation of the infusion and symptomatic treatment. Docetaxel should not be re-administered to patients who have already had a severe allergic reaction.
Skin reactions
Localized skin erythema with edema followed by peeling of the skin at the ends of the extremities (palms and toes) has been observed. Interruption or discontinuation of docetaxel treatment due to severe symptoms such as rash followed by peeling has been reported (see DOSAGE AND ADMINISTRATION).
Fluid retention
Patients may experience severe fluid retention and should be closely monitored for the development of pleural effusions, pericardial effusions, and ascites.
Patients with impaired hepatic function
Patients treated with docetaxel monotherapy at a dose of 100 mg/m2 with serum transaminases (ALT and/or AST) above 1.5 times the upper limit of normal in combination with alkaline phosphatase above 2.5 times the upper limit of normal have an increased risk of serious adverse reactions such as toxic death, including fatal sepsis and gastrointestinal bleeding, febrile neutropenia, infections, platelet reduction, stomatitis, and malaise. Therefore, the recommended dose of docetaxel for these patients with elevated liver function tests (LFTs) is 75 mg/m2 and liver function (LFTs) is tested at baseline and before each cycle (see Dosage and Administration).
When patients have serum bilirubin > upper limit of normal and/or ALT and AST > 3.5 times upper limit of normal with serum alkaline phosphatase > 6 times upper limit of normal, it should not be used unless strictly indicated and no dose reduction is recommended.
There is no information on the use of docetaxel in combination with cisplatin in patients with severe hepatic impairment.
Docetaxel in combination with cisplatin and 5-FU for the treatment of gastric cancer did not include patients with ALT and/or AST>1.5×ULN along with alkaline phosphatase>2.5×ULN and bilirubin>ULN in the pivotal clinical study. It should not be used in such patients unless strictly indicated, and there is no recommendation for dose reduction. There are also no data on docetaxel co-administration in patients with impaired hepatic function in other indications.
Ethanol intake should be noted
Patients with renal impairment
There is no information on the use of docetaxel in patients with severe renal impairment
Neurological
Docetaxel dose should be reduced when signs of severe peripheral neurotoxicity are observed (see Dosage and Administration)
Cardiotoxicity
In patients treated with docetaxel in combination with trastuzumab, particularly after anthracycline-containing therapy (adriamycin or epoetin), the occurrence of heart failure has been observed, which may be moderate to severe and may lead to death (see Adverse Reactions)
When a patient is ready to receive docetaxel in combination with trastuzumab, his or her underlying cardiac status should be evaluated. Monitoring of cardiac function should continue during treatment (e.g., every 3 months) to help confirm whether the patient is experiencing cardiac dysfunction. For more details, see the trastuzumab instruction sheet.
Eye organ abnormalities
As with other paclitaxel drugs, cystoid spot edema has been reported in patients treated with docetaxel, and patients suffering from visual impairment need to undergo prompt and complete ophthalmologic examination. If a patient is diagnosed with cystoid spot edema, docetaxel needs to be discontinued immediately and treated appropriately (see ADVERSE REACTIONS).
Other
Contraception should be used during treatment and for at least three months after the end of treatment.
Other precautions to take with adjuvant chemotherapy for breast cancer
Complicated neutropenia
G-CSF and dose reduction should be considered in patients with concomitant neutropenia (including prolonged neutropenia, febrile neutropenia, or infection) (see Dosage and Administration).
Gastrointestinal Reactions
Early symptoms include: abdominal pain and gastrointestinal sensitivity with or without neutropenia, fever, diarrhea. Severe gastrointestinal toxicity may occur early and should be diagnosed and treated promptly.
Congestive Heart Failure
Patients should be monitored for signs of congestive heart failure during treatment and follow-up. Higher CHF in the first year after treatment has been observed in patients with lymph node positive breast cancer treated with TAC.
Leukemia
Hematologic follow-up is required for the risk of developing delayed spinal cord dysplasia or myeloid leukemia in patients receiving docetaxel, adriamycin, and cyclophosphamide (TAC).
Patients with 4 or more positive lymph nodes
The observed benefit in disease-free survival (DFS) and overall survival (OS) in patients with 4 or more positive lymph nodes did not reach statistical significance; therefore, the positive benefit/risk ratio of TAC in patients with 4 or more positive lymph nodes was not fully confirmed at the time of final analysis.
Excipients
Ethanol may be harmful in patients with alcoholism. The effects of ethanol need to be considered in pregnant or lactating patients, in children and in high-risk groups such as patients with liver disease or epilepsy.
Be aware of possible effects on the central nervous system.
Ethanol may alter the effects of other co-administered drugs.
Studies on effects on driving or machine operation have not been performed. Ethanol may affect driving or machine operation.
Geriatric
In a study conducted in patients with non-small cell lung cancer receiving chemotherapy for the first time (TAX 326), 148 of the patients treated with docetaxel and cisplatin were older than or equal to 65 years of age and 15 patients were older than or equal to 75 years of age; no difference in treatment outcome was found between older and younger patients when they were compared.
Older patients treated with docetaxel and cisplatin showed a trend toward increased incidence of diarrhea and 3/4 degree neurotoxicity in the former compared with older patients receiving vincristine and cisplatin.
In a study of 333 prostate cancer patients receiving a 3-week regimen of docetaxel, 209 patients were 65 years of age or older and 68 patients were 75 years of age or older. No differences in efficacy were shown in older and younger patients. Among patients receiving a 3-week regimen of docetaxel, the incidence of anemia, infection, nail changes, anorexia and weight loss was more than 10% higher in patients 65 years of age or older compared with patients younger than 65 years of age.
In a study of 300 patients with gastric cancer treated with docetaxel combined with a cisplatin and 5-FU regimen (221 from a phase III clinical trial and 79 from a phase II clinical trial), 74 patients were 65 years of age or older and 4 patients were 75 years of age or older. The incidence of serious adverse events was higher in older patients compared with younger patients. The incidence of the following adverse events (all grades): drowsiness, stomatitis, and neutropenic infections was more than 10% higher in patients 65 years of age or older compared to younger patients.
Elderly patients treated with the TCF regimen should be closely monitored.
Recommendations for safe disposition.
Cytotoxic drugs should be administered according to the following guidelines.
Drug compounding should only be performed by trained personnel at designated sites.
Docetaxel is an anticancer drug and extra care should be taken when handling and preparing solutions when used with other toxic compounds.
The work surface should be covered with a disposable plastic laminate.
Wear protective gloves and clothing.
If Docetaxel Injection, pre-injection solution or injection solution comes in contact with skin, wash immediately and thoroughly with soap and water. If Docetaxel Injection, Pre-Infusion Solution or Injection Solution comes in contact with eyes or mucous membranes, wash immediately and thoroughly with water.
Cytotoxic drugs should not be disposed of by pregnant personnel.
Take extra care when disposing of discarded medications.
Pregnant women and nursing mothers]
There is no information on the use of docetaxel in pregnant women. Docetaxel has shown embryotoxicity and fetal toxicity in rabbits and rats, and reduced fertility in rats. As with other cytotoxic drugs, there may be fetal damage when docetaxel is used in pregnant women. Therefore, docetaxel should not be used in pregnant women. Women of childbearing age should be cautioned to avoid pregnancy while on docetaxel therapy and to notify their treating physician immediately if they become pregnant.
Docetaxel is esterophilic, but it is not known whether it can be excreted from human milk.
Also, due to potential adverse effects on nursing infants, breast-feeding should be discontinued during docetaxel treatment.
Pediatric Use]
There is limited experience with docetaxel in children and adolescents.
Geriatric Use]
Geriatric: Based on the results of population pharmacokinetic data, there is no specific guidance for the use of the drug in the elderly.
There is no data on the use of docetaxel in combination with adriamycin and cyclophosphamide in patients aged >70 years.
[Drug Interactions].
No formal clinical data are available to evaluate the interaction of docetaxel with other drugs.
In vitro studies suggest that the metabolism of docetaxel may be altered by the combination of drugs that induce, inhibit, or are metabolized by cytochrome P450-3A (and thus may competitively inhibit this enzyme) such as cyclosporine, terfenadine, ketoconazole, erythromycin, and vinblastine. Caution should be taken when patients combine the above drugs because of the potential for significant drug-to-drug effects.
Combination with CYP3A4 inhibitors may result in slowed metabolism of docetaxel in the body, and its incidence of adverse reactions may increase as a result. If combination with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, indinavir, carbofurazone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole) is unavoidable, close clinical monitoring is required, and dose adjustment may be an appropriate option. In a pharmacokinetic study with seven patients, the combination of docetaxel with a strong inhibitor of CYP3A4 resulted in a reduction in the in vivo clearance of docetaxel of up to 49%.
Docetaxel had a high protein binding rate (>95%). Although the in vivo interaction of docetaxel with other drugs has not been formally studied, in vitro tests have shown that drugs that bind easily to protein such as erythromycin, diphenhydramine, propranolol, propafenone, phenytoin, salicylates, sulfamethoxazole, and sodium valproate do not affect the binding of docetaxel to protein. In addition, dexamethasone did not affect the protein binding of docetaxel. Docetaxel did not affect the protein binding of digitalis toxin.
There was no effect on the pharmacokinetic properties of docetaxel, adriamycin, and cyclophosphamide when they were coadministered. Limited data from a single-agent uncontrolled study suggest an interaction between docetaxel and carboplatin. When combined with docetaxel, the clearance of carboplatin increased by approximately 50% compared to previously reported data for carboplatin alone.
A pharmacokinetic study of docetaxel was conducted in combination with prednisone in patients with metastatic prostate cancer. Docetaxel is metabolized by CYP3A4, and prednisone is a known CYP3A4 inducer. No statistically significant effect of prednisone on docetaxel pharmacokinetics was observed.
[Drug Overdose].
Known symptoms of overdose and disposition.
A few overdoses have been reported. In case of docetaxel overdose, no antidote is available and the patient should be moved to a special care unit and closely monitored for vital signs. Adverse events may occur in the case of overdose. Major complications of overdose that can be anticipated include bone marrow depression, peripheral neurotoxicity, and mucositis. G-CSF therapy should be administered as soon as possible after a patient is found to have overdosed. If needed, other symptomatic treatment should be administered.
Pharmacology and Toxicology
Pharmacological effects
Docetaxel is an antitumor agent that promotes the polymerization of tubules into stable microtubules and inhibits their depolymerization, thereby significantly reducing the number of free tubules. The binding of docetaxel to microtubules does not change the number of protofilaments.
In vitro experiments have shown that docetaxel can disrupt the microtubule meshwork structure, which is important for the function of cells in interphase mitosis.
In vitro experiments have demonstrated that docetaxel is cytotoxic to a variety of mouse and human tumor cell lines. In addition, it has been shown to be cytotoxic to newly excised human tumor cells in clonogenesis assays. The intracellular concentration of docetaxel was high and the retention time was long. In addition, it is active against many tumor cell lines that overexpress P-glycoprotein (encoded by multidrug resistance genes). In in vivo studies, docetaxel has a broad antitumor spectrum with antitumor activity against both advanced mouse and human transplanted tumors, independent of the dosing regimen.
Toxicological effects
Carcinogenic effects
The carcinogenicity of docetaxel has not been studied.
Mutagenicity
Docetaxel has been shown to be mutagenic in in vitro micronucleus and chromosome aberration assays in CHO-K1 cells and in vivo micronucleus assays in mice. However, it was not mutagenic in the Ames assay or in the CHO/HGPRT gene mutation assay. The present results are consistent with the pharmacological activity of docetaxel.
Impairment of reproductive capacity
Adverse reactions in rodent toxicity studies suggest that docetaxel may impair fertility in males.
[Pharmacokinetics].
In a phase I study, the pharmacokinetics of docetaxel were studied in cancer patients at doses ranging from 20-115 mg/m2. The pharmacokinetic characteristics of docetaxel were dose-independent and conformed to a three-compartment pharmacokinetic model with alpha, beta, and gamma half-lives of 4 min, 36 min, and 11.1 h, respectively. The latter phase is partly due to the relatively slow elimination of the drug from the peripheral compartment. The mean peak concentration was 3.7 ug/mL and the AUC was 4.6 h-ug/mL for docetaxel 100 mg/m2 given by intravenous infusion over 1 h. The overall clearance and steady-state volume of distribution were 21 L/h/m2 and 113 L, respectively. The individual variation in total body clearance was approximately 50%. The plasma protein binding rate of docetaxel exceeds 95%.
Docetaxel and its metabolites are mainly excreted in the feces. The amount excreted in the feces and urine is approximately 75% and 6% of the administered dose, respectively, with only a small amount excreted in prototype form. In vitro studies have shown that cytochrome P450-3A isoenzymes are associated with the metabolism of docetaxel, that protein binding of docetaxel exceeds 95%, and that dexamethasone does not affect the binding of docetaxel to protein.
In a 14C-docetaxel study in 3 cancer patients, docetaxel was excreted in urine and feces as a cytochrome P450-mediated 3-butyl ester oxidation metabolite. within 7 days, urinary and fecal excretion accounted for approximately 6% and 75% of the administered radioactivity, respectively, and approximately 80% of the radioactivity was found in the feces during the first 48 hours, including 1 major inactive metabolite and 3 trace inactive metabolites and a very small amount of the prototype drug.
Pharmacokinetic analysis of the docetaxel population was performed in 577 patients. The pharmacokinetic parameters assessed by the model were very close to the results of the phase I clinical study. The pharmacokinetics of docetaxel were independent of the age or sex of the patients. Results of clinical biochemical data in a small number of patients (n=23) showed a mean reduction in total clearance of 27% with mild to moderate hepatic impairment (ALT, AST ≥ 1.5 times ULN with alkaline phosphatase ≥ 2.5 times ULN). (See Dosage and Administration). Docetaxel clearance was unchanged in patients with mild to moderate fluid retention and no data are available on dosing in patients with severe fluid retention.
In combination dosing, docetaxel did not affect the clearance of adriamycin or the plasma concentration of adriamycinol (a metabolite of adriamycin). A study in 30 breast cancer patients found that concomitant administration of docetaxel, adriamycin, and cyclophosphamide did not affect their pharmacokinetic properties.
The Phase I study evaluated capecitabine with docetaxel and showed that capecitabine did not affect the pharmacokinetic properties of docetaxel (Cmax and AUC), nor did docetaxel affect the pharmacokinetic properties of the related metabolite of capecitabine, 5-DFUR (the predominant metabolite of capecitabine).
In combination with cisplatin or carboplatin, docetaxel clearance was similar to that with single dosing. When docetaxel infusion was followed immediately by cisplatin treatment, the pharmacokinetic profile of cisplatin was similar to that of its monotherapy.
Pharmacokinetic studies of 12 patients treated with docetaxel in combination with cisplatin and 5-fluorouracil in solid tumors showed that the combination did not affect the pharmacokinetics of each drug.
The effect of prednisone on the pharmacokinetics of docetaxel was studied in 42 patients using standard dexamethasone prophylaxis. No effect of prednisone on the pharmacokinetics of docetaxel was observed.
Storage】Docetaxel Injection should be stored at 2℃～25℃ and kept in the original package to avoid light.
Keep away from children.
The injection should be used within 6 hours after preparation at 25℃, including a 1-hour intravenous drip to the patient.
Refrigeration will not adversely affect the drug.
Package】Cillin bottle package (medium borosilicate glass controlled injection bottle, copolymer film of PTFE/hexafluoropropylene with chlorinated butyl rubber stopper for injection), 1 pc/box
【Validity】12 months
Execution standard
Approval number】
【Drug marketing license holder
Drug Holder: Chengdu Huiyu Biotechnology Co.
Address: 302, 3/F, Building 2, No. 5, Gaopeng Avenue, Gaoxin District, Chengdu
Postal Code: 610000
Telephone number: 028-86021875
Fax number: 028-83150922
If you have questions, you can contact the drug holder
[Entrusted manufacturer
Manufacturer: Sichuan Huiyu Pharmaceutical Co.
Production address: Neijiang City, Sichuan Province, west of the west side of Road 5, Industrial Park, Lot B
Telephone: 0832-8808045
Docetaxel Injection Instructions for use
Do not mix this product with other double vials of docetaxel injection (concentrated solution and solvent).
Read all the contents before preparing Docetaxel Intravenous Injection.
Prescription
Docetaxel Injection (1ml:20mg) is a colorless to brownish yellow clear liquid which is a solution of anhydrous docetaxel dissolved in polysorbate 80 and anhydrous ethanol.
Specification
One box contains one docetaxel injection 1ml:20mg.
2.1 Docetaxel 1ml:20mg solution:
Each docetaxel 1ml:20mg is packed in a 6ml clear glass vial with a green easy-open elastic cap.
1ml:20mg is made by dissolving docetaxel in polysorbate 80 and anhydrous ethanol at a concentration of 20mg/ml.
Docetaxel Injection 1ml:20mg should be stored in the original package at 2~25℃ away from light. Under these storage conditions, the validity of unopened docetaxel injection is 12 months. The product should not be used after the expiration date indicated on the outer packaging box.
2.2 Stability after compounding
The prepared infusion bag solution should be used within 6 hours at 25°C (including a 1-hour intravenous drip to the patient).
In addition, physicochemical properties indicate that formulated docetaxel injection in a non-PVC infusion bag is stable for 48 hours when stored at 2-8°C.
Docetaxel infusion is a supersaturated solution and therefore will crystallize over time. If crystallization occurs, the infusion should be discarded.
3. Recommendations for safe use
Docetaxel is an antineoplastic drug and, like other toxic compounds, must be handled and prepared with the utmost care and the use of gloves is recommended.
If docetaxel solution, pre-injection solution or injection solution touches the skin, rinse immediately and thoroughly with soap and water; if it touches mucous membranes, rinse immediately and thoroughly with water.
4. Preparation of intravenous injection
Docetaxel Injection 1ml:20mg can be added to the infusion without dilution with solvent.
Each bottle is for single use and should be used immediately after opening.
5. Disposal
All items used for dilution and injection are disposed of according to standard operating procedures.