Medicinal Products

DOCETAXEL TEVA 80 mg 10 mg / mL

Generic drug of Taxotere
Therapeutic class: Oncology and hematology
active ingredients: Docetaxel
laboratory: Teva Pharma BV

Solution for solution and solvent for IV infusion
Box of 1 Bottle of 2.88 ml + solvent bottle of 5.12 ml
All forms

Indication

Breast cancer

Docetaxel Teva in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of operable breast cancer in patients with lymph node involvement.

Docetaxel Teva in combination with doxorubicin is indicated for the treatment of locally advanced or metastatic breast cancer in patients who have not received prior cytotoxic chemotherapy for this condition.

Docetaxel Teva is indicated as monotherapy in the treatment of patients with locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy, including an anthracycline or alkylating agent.

Docetaxel Teva in combination with trastuzumab is indicated for the treatment of metastatic breast cancer with tumor over-expression of HER2 in patients who have not been pre-treated with chemotherapy for metastatic disease.

Docetaxel Teva in combination with capecitabine is indicated for the treatment of locally advanced or metastatic breast cancer after failure of cytotoxic chemotherapy with an anthracycline.

Non-small cell lung cancer

Docetaxel Teva is indicated for the treatment of locally advanced or metastatic non-small cell lung cancer after failure of prior chemotherapy.

Docetaxel Teva in combination with cisplatin is indicated for the treatment of unresectable, locally advanced or metastatic non-small cell lung cancer in patients who have not received prior chemotherapy for this indication.

Prostate cancer

Docetaxel Teva in combination with prednisone or prednisolone is indicated for the treatment of metastatic hormone-resistant prostate cancer.

Gastric cancer

Docetaxel Teva in combination with cisplatin and 5-fluorouracil is indicated for the treatment of metastatic gastric adenocarcinoma, including gastroesophageal junction adenocarcinoma, in patients who have not been pre-treated with chemotherapy for metastatic disease.

Cancer of the upper aero-digestive tract

Docetaxel Teva in combination with cisplatin and 5-fluorouracil is indicated for the induction therapy of locally advanced squamous cell carcinoma of the upper aerodigestive tract.

Dosage DOCETAXEL TEVA 80 mg 10 mg / mL Concentrate for solution and solvent for infusion IV Box of 1 Bottle of 2.88 ml + vial of solvent of 5.12 ml

The use of docetaxel should be restricted to specialized cytotoxic units and docetaxel should be administered under the supervision of a physician qualified in the use of anticancer chemotherapy (see section on Instructions for use, handling and treatment). elimination ).

Recommended dosage:

In breast, non-small-cell lung, gastric and upper aero-digestive tract cancers, and unless contraindicated, premedication with an oral corticosteroid may be used, such as dexamethasone at a dose of 16 mg per day ( for example: 8 mg twice daily) for 3 days starting the day before the infusion of docetaxel (see Warnings and Precautions ). G-CSF prophylaxis can be used to reduce the risk of haematological toxicity. In prostate cancer, given the concomitant use of prednisone or prednisolone, the recommended oral premedication of dexamethasone is 8 mg, 12 hours, 3 hours and 1 hour prior to docetaxel infusion (see section 4.4). and precautions for use ).

Docetaxel is given as a one-hour infusion every three weeks.

Breast cancer :

In the adjuvant treatment of operable breast cancer with nodal involvement, the recommended dose of docetaxel is 75 mg / m² administered 1 hour after 50 mg / m² doxorubicin and 500 mg / m² cyclophosphamide every 3 weeks for 6 cycles. (see Dosage Adjustment).

For the treatment of patients with locally advanced or metastatic breast cancer, the recommended dose of docetaxel monotherapy is 100 mg / m². In the first line, docetaxel at the recommended dose of 75 mg / m² is associated with doxorubicin (50 mg / m²).

In combination with trastuzumab, the recommended dose of docetaxel is 100 mg / m² every 3 weeks, in combination with trastuzumab administered weekly. In the pivotal study, the first docetaxel infusion was performed the day after the first administration of trastuzumab. The following courses of docetaxel were given immediately after the completion of the trastuzumab infusion if the previous dose of trastuzumab had been well tolerated. For the dosage and method of administration of trastuzumab, see the Summary of Product Characteristics.

In combination with capecitabine, the recommended dose of docetaxel is 75 mg / m² every three weeks, combined with 1250 mg / m² of capecitabine twice daily (within 30 minutes after a meal) for two weeks followed by a period without treatment of one week. For capecitabine dose calculations based on body surface area, see capecitabine summary of product characteristics.

Non-small cell lung cancer:

In patients treated for non-small cell lung cancer who received no prior chemotherapy, the recommended doses are 75 mg / m² docetaxel followed immediately by 75 mg / m² cisplatin in 30-60 minutes. After failure of platinum-based chemotherapy, the recommended dose is 75 mg / m² of docetaxel monotherapy.

Prostate cancer :

The recommended dosage of docetaxel is 75 mg / m². Prednisone or oral prednisolone is administered continuously at a dose of 5 mg twice daily (see section 5.1 Pharmacodynamic properties ).

Gastric cancer:

The recommended dose of docetaxel is 75 mg / m 2 followed on the same day by a 1 to 3 hour infusion of cisplatin at a dose of 75 mg / m 2. Immediately after the end of the cisplatin infusion, the 5-day continuous infusion of 5-fluorouracil is initiated at a dose of 750 mg / m² / day. The treatment is repeated every 3 weeks. Premedication with anti-emetics and adequate hydration prior to cisplatin administration should be performed. G-CSF prophylaxis should be used to reduce the risk of hematologic toxicity (see also dose adjustments during treatment).

Cancer of the upper aero-digestive tract:

Patients should be premedicated with anti-emetics and adequate hydration (before and after administration of cisplatin). G-CSF prophylaxis can be used to reduce the risk of haematological toxicity. All docetaxel arm patients in TAX323 and TAX324 were given antibiotic prophylaxis.

• Induction chemotherapy followed by radiotherapy (TAX323). In the induction treatment of locally advanced and inoperable squamous cell carcinoma of the upper aero-digestive tract, the recommended dose of docetaxel is 75 mg / m² infused over one hour, followed by cisplatin at a dosage of 75 mg / m² infusion. from 1 hour to D1, followed by 5-fluorouracil at a dosage of 750 mg / m² / day in continuous infusion over 5 days. This pattern is repeated every 3 weeks for 4 cycles. After chemotherapy, patients should be treated with radiotherapy.

• Induction chemotherapy followed by chemoradiotherapy (TAX324). In the induction treatment of patients with locally advanced squamous cell carcinoma of the upper aero-digestive tract (VADS) (unresectable technically, low probability of surgical curability or organ preservation), the recommended dosage of docetaxel is 75 mg / m² by intravenous infusion for 1 hour on D1, followed by cisplatin at the dosage of 100 mg / m² in infusion from 30 minutes to 3 hours, followed by 5-fluorouracil 1000 mg / m² / day in continuous infusion from D1 to D4. This schedule is administered every 3 weeks at 3 cycles. After chemotherapy, patients should be treated with chemoradiotherapy.

For dosage adjustments of cisplatin and 5-fluorouracil, refer to the summary of the corresponding product characteristics.

Dosage adjustment:

Overview

Docetaxel should not be administered until the number of neutrophils is less than 1500 / mm 3 . In patients who during treatment with docetaxel experienced febrile neutropenia, neutrophils <500 / mm 3 for more than 1 week, severe or repeated skin reactions or severe peripheral neuropathy, docetaxel must be reduced from 100 mg / m² to 75 mg / m² and / or from 75 to 60 mg / m². If these reactions persist at 60 mg / m², treatment should be discontinued.

Adjuvant treatment of breast cancer

In the pivotal study, in patients who received adjuvant treatment for breast cancer and who had complicated neutropenia (including prolonged neutropenia, febrile neutropenia, or infection), it was recommended that G -CSF prophylactically (ex: from 4th to 11th day) for all subsequent cycles. Patients who continued to have this effect should remain under G-CSF and the dose of docetaxel should be decreased to 60 mg / m². However, in clinical practice, neutropenia may occur sooner. Therefore, the use of G-CSF should be considered according to the neutropenic risk of the patient and the recommendations in force. For patients with grade 3 or 4 stomatitis, the dose of docetaxel should be decreased to 60 mg / m².

In combination with cisplatin

In patients who received an initial dose of docetaxel 75 mg / m 2 in combination with cisplatin, for whom nadir platelet count at the previous course of treatment was <25000 / mm 3, or with febrile neutropenia or toxicities severe non-haematological, the dose of docetaxel should be reduced to 65 mg / m² in subsequent cycles. For dosage adjustment of cisplatin, refer to the Summary of Product Characteristics.

In combination with capecitabine

• For dosage adjustment of capecitabine, see its summary of product characteristics.

• In patients with a first appearance of Grade 2 toxicity, which persists until the next dose of docetaxel / capecitabine, delay treatment until returning to Grade 0-1, then continue at 100% initial dosages. .

• In patients with 2nd Grade 2 toxicity or Grade 3 toxicity, regardless of the stage of the treatment cycle, delay treatment until returning to Grade 0-1 and resume treatment with 55 mg / m².

• For any subsequent appearance of toxicity, or any Grade 4 toxicity, discontinue docetaxel therapy.

For dosage modifications of trastuzumab, see the Summary of Product Characteristics.

In combination with cisplatin and 5-fluorouracil

If an episode of complicated neutropenia (febrile, prolonged, or neutropenic) occurs despite the use of G-CSF, the dosage of docetaxel should be reduced from 75 to 60 mg / m². If other episodes of complicated neutropenia occur, the dosage of docetaxel should be reduced from 60 to 45 mg / m². In Grade 4 thrombocytopenia, the dose of docetaxel should be reduced from 75 to 60 mg / m². The following administrations of docetaxel should be resumed only if the number of neutrophils is> 1500 / mm 3 and the number of platelets is> 100 000 / mm 3 . If these haematological toxicities persist treatment should be stopped (see Warnings and precautions for use ). In case of toxicities, the dose adjustments of patients receiving docetaxel in combination with cisplatin and 5-fluorouracil (5-FU) are as follows:

Toxicity

Dosage adjustments

Diarrhea grade 3

1st episode: 20% reduction in the dose of 5-FU.

2nd episode: 20% reduction of the dose of docetaxel.

Diarrhea grade 4

1st episode: 20% reduction in the dose of docetaxel and 5-FU. 2nd episode: stop treatment.

Stomatitis / mucositis grade 3

1st episode: 20% reduction in the dose of 5-FU.

2nd episode: final shutdown of 5-FU only.

3rd episode: 20% reduction of the dose of docetaxel.

Stomatitis / mucositis grade 4

1st episode: final stop of 5-FU only.

2nd episode: 20% reduction of the dose of docetaxel.

For dosage adjustments for 5-fluorouracil and cisplatin, refer to the summary of product characteristics.

In pivotal studies in patients treated with induction chemotherapy for VADS cancer, and who had complicated neutropenia (including prolonged neutropenia, febrile neutropenia, or infection), G-CSF prophylaxis (eg, 6 th to 15 th day) was recommended for subsequent cycles.

Populations at risk

Patients with hepatic insufficiency

Based on the pharmacokinetic data for docetaxel 100 mg / m 2 monotherapy, the recommended dose of docetaxel in patients with transaminases (ALT and / or ASAT) greater than 1.5 times the upper limit of normal ( ULN) and alkaline phosphatase greater than 2.5 times the ULN is 75 mg / m 2 (see sections Warnings and Precautions and Pharmacokinetic Properties ). In patients with bilirubin> 1 x ULN and / or AST and ALT 3.5 times ULN and alkaline phosphatase> 6 x ULN, no dose reduction may be recommended and docetaxel is not recommended. should not be administered unless it is strictly indicated. In the treatment of gastric adenocarcinoma, in combination with cisplatin and 5-fluorouracil, the pivotal clinical study excluded patients with transaminase levels (ASAT and / or ALT)> 1.5 times the ULN associated with alkaline phosphatase> 2.5 x ULN and bilirubin> 1 x ULN: therefore for these patients no dose reduction can be recommended and docetaxel should not be administered unless strictly indicated. There is no data on hepatic impairment treated with docetaxel in combination with other indications.

Children and adolescents:

Use in children is limited.

Elderly

In view of the population pharmacokinetic data, no special precautions are to be taken in the elderly. In combination with capecitabine, it is recommended that the initial dose of capecitabine be reduced to 75% in subjects 60 years of age or older (see summary of capecitabine product characteristics).

Against indications

Hypersensitivity to the active substance or to any of the excipients.

Docetaxel should not be used in patients with an initial neutrophil count <1500 / mm 3 .

In the absence of available data, docetaxel should not be administered to patients with severe hepatic impairment (see sections Posology and method of administration and Warnings and precautions for use ).

Also take into account the contraindications of the specialties associated with docetaxel.

Adverse effects Docetaxel Teva 80 MG

Adverse reactions believed to be possibly or probably related to the administration of docetaxel have been reported in:

• 1312 and 121 patients receiving 100 mg / m² and 75 mg / m² of docetaxel monotherapy, respectively.

• 258 patients who received docetaxel in combination with doxorubicin.

• 406 patients who received docetaxel in combination with cisplatin.

• 92 patients who received docetaxel in combination with trastuzumab.

• 255 patients who received docetaxel in combination with capecitabine.

• 332 patients who received docetaxel in combination with prednisone or prednisolone (clinically important and treatment-related adverse events are presented).

• 744 patients who received docetaxel in combination with doxorubicin and cyclophosphamide (clinically relevant and treatment-related adverse events are presented below).

• 300 patients with gastric adenocarcinoma (221 patients in phase III and 79 patients in phase II) who received docetaxel in combination with cisplatin and 5-fluorouracil (clinically relevant and treatment-related adverse events are presented below) .

• 174 and 251 patients with upper aerodigestive tract cancer treated with docetaxel in combination with cisplatin and 5-fluorouracil (clinically relevant and treatment-related adverse events are presented below).

These events have been described using the NCI Common Criteria for Toxicity (grade 3 = G3, grade 3-4 = G3 / 4, grade 4 = G4) and COSTART terms. Frequencies are defined as: very common (≥1 / 10), frequent (≥1 / 100 to <1/10); uncommon (≥1 / 1000 to <1/100); rare (≥1 / 10, 000 to <1/1000); very rare (<1/10000), not known (can not be estimated based on available data).

Within each frequency group, adverse effects are presented in descending order of severity.

The most commonly observed adverse events when using docetaxel monotherapy are: neutropenia (reversible and non-cumulative, median nadir onset and median duration of severe neutropenia (<500 / mm 3 ) were 7 days), anemia, alopecia, nausea, vomiting, stomatitis, diarrhea and asthenia. The severity of the undesirable effects of docetaxel may be increased when combined with other cytotoxics.

For association with trastuzumab, adverse effects (all grades) reported in at least 10% of cases are presented. An increase in the incidence of serious adverse events (40% vs. 31%) and Grade 4 adverse events (34% vs. 23%) was observed for the combination with trastuzumab compared with docetaxel monotherapy.

For the combination with capecitabine, the most commonly reported adverse events (≥5%) in a phase III study in patients treated for breast cancer after failure of treatment with an anthracycline are presented (see summary of characteristics of capecitabine).

The following side effects have been commonly observed with docetaxel:

Immune system disorders

Hypersensitivity reactions generally occurred within minutes of starting a docetaxel infusion and were usually mild to moderate. The most commonly reported symptoms were flushes, rash with or without pruritus, chest tightness, low back pain, dyspnea and fever or chills. Intense reactions were characterized by hypotension and / or bronchospasm or general rash / erythema (see Warnings and Precautions section ).

Nervous system disorders:

The occurrence of severe peripheral neurotoxicity requires a dose reduction (see sections Posology and method of administration and Warnings and precautions for use ). Mild to moderate neurosensory signs are characterized by paresthesia, dysesthesia or pain-like burning sensations. Neuromotor manifestations are mainly characterized by weakness.

Skin and subcutaneous tissue disorders:

Reversible skin reactions were observed and were generally considered mild to moderate. Reactions were characterized by rash with localized eruptions mainly in the feet and hands (including severe hand-foot syndromes) but also in the arms, face or chest, and frequently associated with pruritus. These eruptions usually occurred in the week following the infusion of docetaxel. Severe symptoms such as eruptions followed by desquamation, rarely leading to temporary or definitive discontinuation of docetaxel, have been reported less frequently (see section 4.2). Posology and method of administration and Warnings and Precautions employment ). Severe nail disorders are characterized by hypo or hyperpigmentation of the nails and sometimes pain and onycholysis.

General disorders and administration site defects:

Injection site reactions were generally minor and manifested by hyperpigmentation, inflammation, redness or dryness of the skin, phlebitis or extravasation, and swelling of the vein.

Fluid retention may result in peripheral edema and, less commonly, pleural effusion, pericardial effusion, ascites, and weight gain. Peripheral edema usually begins in the lower limbs and can be generalized with a weight gain of 3 kg or more. Fluid retention is cumulative in incidence and severity (see Warnings and Precautions section ).

Docetaxel 100 mg / m² monotherapy

MedDRA class-organ system

Very frequent effects

Frequent effects

Infrequent effects

Infections and infestations

Infections (G3 / 4: 5.7%, including sepsis and pneumonia, fatal in 1.7% of cases)

Infection associated with grade 4 neutropenia (G3 / 4: 4.6%)

affections

hematologic and lymphatic system

Neutropenia (G4:

76.4%);

Anemia (G3 / 4: 8.9%);

Febrile neutropenia

Thrombocytopenia (G4:

0.2%)

Immune system disorders

Hypersensitivity (G3 / 4: 5.3%)

Metabolism and nutrition disorders

Anorexia

Nervous system disorders

Peripheral sensory neuropathy (G3: 4.1%);

Peripheral motor neuropathy (G3 / 4: 4%) Dysgeusia (severe 0.07%)

Heart conditions

Arrhythmia (G3 / 4: 0.7%)

Heart failure

Vascular disorders

hypotension;

Hypertension;

Hemorrhage

Respiratory, thoracic and mediastinal disorders

Dyspnoea (severe: 2.7%)

Gastrointestinal disorders

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 haemorrhage (severe 0.3%)

Esophagitis (severe: 0.4%)

Skin and subcutaneous tissue disorders

Alopecia; Cutaneous reactions (G3 / 4: 5.9%); Nail Alteration (severe: 2.6%)

Musculoskeletal and systemic disorders

Myalgia (severe: 1.4%)

arthralgia

General disorders and administration site conditions

Fluid retention (severe: 6.5%) Asthenia (severe: 11.2%); Pain

Reaction at the injection site; Chest pain of non-cardiac origin (severe: 0.4%)

Elevation of bilirubin (G3 / 4 <5%);

Elevation of alkaline phosphatases (G3 / 4 <4%); Elevation of ASAT (G3 / 4 <3%); ALT elevation (G3 / 4 <2%)

investigations


Blood and lymphatic system disorders

Rare: bleeding episodes associated with grade 3/4 thrombocytopenia.

Nervous system disorders

Reversibility data are available for 35.3% of patients with neurotoxic manifestations following docetaxel monotherapy at 100 mg / m². These effects were spontaneously reversible within 3 months.

Skin and subcutaneous tissue disorders

Very rare: 1 case of non-reversible alopecia at the end of the study. 73% of the skin reactions were reversible within 21 days.

General disorders and administration site conditions

For fluid retention, the median cumulative dose at discontinuation was greater than 1000 mg / m² and the median reversal time was 16.4 weeks (range 0 to 42 weeks).

The onset of moderate to severe fluid retention is delayed (median cumulative dose:

818.9 mg / m²) in patients who received premedication compared to patients who did not receive premedication (median cumulative dose: 489.7 mg / m²); however, this event has been reported in some patients during the first cycles of treatment.

Docetaxel 75 mg / m² monotherapy

MedDRA class-organ system

Very frequent effects

Frequent effects

Infections and infestations

Infections (G3 / 4: 5%)

Blood and lymphatic system disorders

Neutropenia a (G4: 54.2%); Anemia (G3 / 4: 10.8%); Thrombocytopenia (G4: 1.7%)

Febrile neutropenia

Immune system disorders

Hypersensitivity (non-severe)

Metabolism and nutrition disorders

Anorexia

Nervous system disorders

Peripheral sensory neuropathy (G3 / 4: 0.8%)

Peripheral motor neuropathy (G3 / 4: 2.5%)

Heart conditions

Arrhythmia (never severe)

Vascular disorders

hypotension

Gastrointestinal 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

Alopecia;

Skin reactions (G3 / 4:

0.8%)

Nail Alteration (Severe 0.8%)

Musculoskeletal and systemic disorders

myalgia

General disorders and administration site conditions

Asthenia (severe: 12.4%); Fluid retention (severe 0.8%);

Pain

investigations

Elevation of bilirubin

(G3 / 4 <2%)


Docetaxel 75 mg / m² in combination with doxorubicin

MedDRA class-organ system

Very frequent effects

Frequent effects

Infrequent effects

Infections and infestations

Infection (G3 / 4: 7.8%)

affections

hematologic and lymphatic system

Neutropenia (G4:

91.7%);

Anemia (G3 / 4: 9.4%);

Febrile neutropenia;

thrombocytopenia

(G4: 0.8%)

Immune system disorders

Hypersensitivity (G3 / 4: 1.2%)

Metabolism and nutrition disorders

Anorexia

Nervous system disorders

Peripheral sensory neuropathy (G3: 0.4%)

Peripheral motor neuropathy (G3 / 4: 0.4%)

Heart conditions

Heart failure; Arrhythmia (never severe)

Vascular disorders

hypotension

Gastrointestinal disorders

Nausea (G3 / 4: 5%);

Stomatitis (G3 / 4:

7.8%);

Diarrhea (G3 / 4: 6.2%);

Vomiting (G3 / 4:

5%);

Constipation

Skin and subcutaneous tissue disorders

Alopecia;

Nail alteration (severe: 0.4%); Skin reactions (never severe)

Musculoskeletal and systemic disorders

myalgia

General disorders and administration site conditions

Asthenia (severe:

8.1%);

Water retention

(severe: 1.2%);

pains

Injection site reactions

investigations

Increased bilirubin (G3 / 4 <2.5%);

Increased alkaline phosphatase (G3 / 4 <2.5%)

Increase in ASAT (G3 / 4 <1%) Increase in ALAT (G3 / 4 <1%)


Docetaxel 75 mg / m² in combination with cisplatin

MedDRA class-organ system

Very frequent effects

Frequent effects

Infrequent effects

Infections and infestations

Infection (G3 / 4: 5.7%)

Blood and lymphatic system disorders

Neutropenia (G4:

51.5%);

Anemia (G3 / 4: 6.9%);

Thrombocytopenia (G4: 0.5%)

Febrile neutropenia

Immune system disorders

Hypersensitivity (G3 / 4 2.5%)

Metabolism and nutrition disorders

Anorexia

Nervous system disorders

Peripheral sensory neuropathy (G3: 3.7%); Peripheral motor neuropathy (G3 / 4: 2%)

Heart conditions

Arrhythmia (G3 / 4: 0.7%)

Heart failure

Vascular disorders

Hypotension (G3 / 4: 0.7%)

Gastrointestinal disorders

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

Alopecia;

Nail alteration (severe 0.7%);

Skin reactions (G3 / 4: 0.2%)

Musculoskeletal and systemic disorders

Myalgia (severe: 0.5%)

General disorders and administration site conditions

Asthenia (severe 9.9%);

Water retention

(severe

0.7%);

Fever (G3 / 4: 1.2%)

Feedback to the site

injection;

pains

investigations

Increased bilirubin (G3 / 4 2.1%); Increase in ALT (G3 / 4 1.3%)

Increase in ASAT (G3 / 4 0.5%); G3 / 4 Increased alkaline phosphatase (G3 / 4 0.3%)


Docetaxel 100 mg / m² in combination with trastuzumab

MedDRA class-organ system

Very frequent effects

Frequent effects

Blood and lymphatic system disorders

Neutropenia (G3 / 4: 32%); Febrile neutropenia (including neutropenia associated with fever and antibiotic use) or neutropenia with sepsis

Metabolism and nutrition disorders

Anorexia

Psychiatric disorders

Insomnia

Nervous system disorders

paresthesia; headache; dysgeusia; Hypoaesthesia

Eye disorders

Increased tearing Conjunctivitis

Heart conditions

Heart failure

Vascular disorders

lymphedema

Respiratory, thoracic and mediastinal disorders

Epistaxis; Pharyngolaryngeal pain; nasopharyngitis; Dyspnea; Cough; rhinorrhea

Gastrointestinal disorders

nausea; Diarrhea; vomiting; Constipation; stomatitis; Dyspepsia; Abdominal pain

Skin and subcutaneous tissue disorders

Alopecia; Erythema; rash; Alteration of the nails

Musculoskeletal and systemic disorders

myalgia; arthralgia; Pain of the extremities; Bone pain, Back pain

General disorders and administration site conditions

Asthenia; Peripheral edema; Fever; Tired; Inflammation of the mucous membranes; pain; flu-like syndrome; Chest pain; Chills

Lethargy

investigations

Increase in weight


Heart conditions

Symptomatic heart failure was reported in 2.2% of patients receiving docetaxel plus trastuzumab, compared to 0% of patients receiving docetaxel alone. In the docetaxel arm associated with trastuzumab, 64% of patients had previously received anthracycline as adjunctive therapy, compared to 55% in the docetaxel arm alone.

Blood and lymphatic system disorders

Very common: Hematologic toxicity was higher in patients receiving trastuzumab and docetaxel than in those receiving docetaxel alone (G 3/4 neutropenia: 32% vs. 22%, based on NCI-CTC criteria). It is possible that these figures are underestimated since according to the nadir blood count, docetaxel monotherapy at the dose of 100 mg / m² is known to cause neutropenia in 97% of patients, 76% of grade 4. The The incidence of febrile neutropenia / neutropenia with sepsis was also increased in patients treated with trastuzumab in combination with docetaxel compared to those treated with docetaxel alone (23% vs. 17%).

Docetaxel 75 mg / m² in combination with capecitabine

MedDRA class-organ system

Very frequent effects

Frequent effects

Infections and infestations

Oral candidiasis (G3 / 4: <1%)

Blood and lymphatic system disorders

Neutropenia (G3 / 4: 63%); Anemia (G3 / 4: 10%)

Thrombocytopenia (G3 / 4: 3%)

Metabolism and nutrition disorders

Anorexia (G3 / 4: 1%); Decreased appetite

Dehydration (G3 / 4: 2%);

Nervous system disorders

Dysgeusia (G3 / 4: <1%); Paresthesia (G3 / 4: <1%)

Dizziness;

Headache (G3 / 4: <1%);

Peripheral neuropathy

Eye disorders

Increased tearing

Respiratory, thoracic and mediastinal disorders

Pharyngolaryngeal pain (G3 / 4: 2%)

Dyspnoea (G3 / 4: 1%);

Cough (G3 / 4: <1%);

Epistaxis (G3 / 4: <1%)

Gastrointestinal disorders

Stomatitis (G3 / 4: 18%); Diarrhea (G3 / 4: 14%); Nausea (G3 / 4: 6%); Vomiting (G3 / 4: 4%); Constipation (G3 / 4: 1%); Abdominal pain (G3 / 4: 2%); Dyspepsia

Epigastric pain; Dryness of the mouth

Skin and subcutaneous tissue disorders

Hand foot syndrome (G3 / 4:

24%)

Alopecia (G3 / 4: 6%);

Nail Alteration (G3 / 4:

2%)

dermatitis;

Eruption erythematous (G3 / 4:

<1%);

Discoloration of the nails;

Onycholysis (G3 / 4: 1%)

Musculoskeletal and systemic disorders

Myalgia (G3 / 4: 2%); Arthralgia (G3 / 4: 1%)

Pains of extremities (G3 / 4:

<1%);

Back pain (G3 / 4: 1%);

General disorders and administration site conditions

Asthenia (G3 / 4: 3%);

Fever (G3 / 4: 1%);

Fatigue / weakness (G3 / 4: 5%); Peripheral edema (G3 / 4: 1%);

Lethargy;

pains

investigations

Decrease in weight Increased bilirubin (G3 / 4 9%)


Docetaxel 75 mg / m² in combination with prednisone or prednisolone

MedDRA class-organ system

Very frequent effects

Frequent effects

Infections and infestations

Infection (G3 / 4: 3.3%)

Blood and lymphatic system disorders

Neutropenia (G3 / 4: 32%); Anemia (G3 / 4: 4.9%)

Thrombocytopenia (G3 / 4: 0.6%) Febrile neutropenia

Immune system disorders

Hypersensitivity (G3 / 4: 0.6%)

Metabolism and nutrition disorders

Anorexia (G3 / 4: 0.6%)

Nervous system disorders

Peripheral sensory neuropathy (G3 / 4: 1.2%); Dysgeusia (G3 / 4: 0%)

Peripheral motor neuropathy (G3 / 4: 0%)

Eye disorders

Increased tearing (G3 / 4, 0.6%)

Heart conditions

Decrease in left ventricular ejection fraction (G3 / 4: 0.3%)

Respiratory, thoracic and mediastinal disorders

Epistaxis (G3 / 4: 0%);

Dyspnoea (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%)

Skin and subcutaneous tissue disorders

Alopecia;

Altered nails (never

severe)

Exfoliative rash (G3 / 4: 0.3%)

Musculoskeletal and systemic disorders

Arthralgia (G3 / 4: 0.3%);

Myalgia (G3 / 4: 0.3%)

General disorders and administration site conditions

Fatigue (G3 / 4: 3.9%); Fluid retention (severe 0.6%)


Docetaxel 75 mg / m² in combination with doxorubicin and cyclophosphamide

MedDRA class-organ system

Very frequent effects

Frequent effects

Infrequent effects

Infections and infestations

Infection (G3 / 4: 3.2%); Neutropenic infection. There was no septic death.

affections

hematologic and lymphatic system

Anemia (G3 / 4: 4.3%);

Neutropenia (G3 / 4: 65.5%);

Thrombocytopenia (G3 / 4: 2.0%);

Febrile neutropenia

Immune system disorders

Hypersensitivity (G3 / 4: 1.1%)

Metabolism and nutrition disorders

Anorexia (G3 / 4:

2.2%)

Nervous system disorders

Dysgeusia (G3 / 4: 0.7%);

Peripheral sensory neuropathy (G3 / 4: 0%)

Motor neuropathy

peripheral

(G3 / 4: 0%);

unrest

neurocorticaux

(G3 / 4: 0.3%);

unrest

neurocerebelleux

(G3 / 4:

0.1%)

Syncope (G3 / 4: 0%)

Eye disorders

Lachrymation (G3 / 4: 0.1%); Conjunctivitis (G3 / 4: 0.3%)

Heart conditions

Arrhythmia (G3 / 4: 0.1%), Congestive Heart Failure

Vascular disorders

Vasodilatation (G3 / 4: 0.9%)

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: 5.1%);

Stomatitis (G3 / 4: 7.1%);

Vomiting (G3 / 4:

4.3%);

Diarrhea (G3 / 4: 3.2%);

Constipation (G3 / 4: 0.4%)

Abdominal pain (G3 / 4: 0.5%)

Colitis / enteritis / extensive intestinal perforation

Skin and subcutaneous tissue disorders

Alopecia; Dermal toxicity (G3 / 4 0.7%); Nail Alteration (G3 / 4 0.4%)

Musculoskeletal and systemic disorders

Myalgia (G3 / 4: 0.8%);

Arthralgia (G3 / 4: 0.4%)

Disorders of reproductive organs and breast

Amenorrhea

General disorders and administration site conditions

Asthenia (G3 / 4:

11%);

Fever (G3 / 4: 1.2%);

Peripheral edema

(G3 / 4: 0.4%)

investigations

Loss or weight gain (G3 / 4: 0.3%)


Heart conditions

Congestive heart failure (2.3% with a median follow-up of 70 months) was also reported. One patient in each arm died of heart failure.

Nervous system disorders

In 73 patients with peripheral sensory neuropathy at the end of chemotherapy, neurosensory disorders persisted in 9 patients after a median follow-up of 55 months.

Skin and subcutaneous tissue disorders

Of the 687 patients who had alopecia at the end of chemotherapy, alopecia persisted in 22 patients after a median follow-up of 55 months.

General disorders and administration site conditions

Of the 112 patients who experienced peripheral edema at the end of chemotherapy, peripheral edema persisted in 18 patients after a median follow-up of 55 months.

Disorders of reproductive organs and breast

Of the 233 patients who had amenorrhea at the end of chemotherapy, amenorrhea persisted in 133 patients after a median follow-up of 55 months.

Docetaxel 75 mg / m² in combination with cisplatin and 5-fluorouracil in gastric adenocarcinoma:

MedDRA class-organ system

Very frequent effects

Frequent effects

Infections and infestations

Neutropenic infection;

Infection (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 (G3 / 4: 1.7%)

Metabolism and nutrition disorders

Anorexia (G3 / 4: 11.7%)

Nervous system disorders

Peripheral sensory neuropathy (G3 / 4: 8.7%)

Dizziness (G3 / 4: 2.3%); Peripheral motor neuropathy (G3 / 4: 1.3%)

Eye disorders

Increased tearing (G3 / 4: 0%)

Affections of the ear and labyrinth

Hearing disorders (G3 / 4: 0%)

Heart conditions

Arrhythmia (G3 / 4: 1.0%)

Gastrointestinal disorders

Diarrhea (G3 / 4: 19.7%);

Nausea (G3 / 4: 16%);

Stomatitis (G3 / 4: 23.7%); Vomiting (G3 / 4: 14.3%)

Constipation (G3 / 4: 1.0%); Gastrointestinal pain (G3 / 4: 1.0%); Esophagitis / dysphagia / odynophagia (G3 / 4: 0.7%)

Skin and subcutaneous tissue disorders

Alopecia (G3 / 4: 4.0%)

Rash, itching (G3 / 4: 0.7%); Nail Alteration (G3 / 4: 0.7%); Desquamation (G3 / 4: 0%)

General disorders and administration site conditions

Lethargy (G3 / 4: 19.0%);

Fever (G3 / 4: 2.3%);

Fluid retention (severe / life-threatening: 1%)


Blood and lymphatic system disorders

Febrile neutropenia and neutropenic infection occurred in 17.2% and 13.5%, respectively, regardless of the use of G-CSF. G-CSF was used for secondary prophylaxis in 19.3% of patients (10.7% of chemotherapy cycles). Febrile neutropenia and neutropenic infection occurred in 12.1% and 3.4%, respectively, of patients who received G-CSF prophylaxis and 15.6% and 12.9% of patients who did not receive G-CSF. -CSF (see paragraph Posology and method of administration ).

Docetaxel 75 mg / m² in combination with cisplatin and 5-fluorouracil in cancers of the upper aero-digestive tract

• Induction chemotherapy followed by radiotherapy (TAX323)

MedDRA class-organ system

Very frequent effects

Frequent effects

Infrequent effects

Infections and infestations

Infections (G3 / 4: 6.3%)

infections

neutropenic

Benign and malignant tumors (including cysts and polyps)

Cancer pain (G3 / 4: 0.6%)

affections

hematologic and lymphatic system

Neutropenia (G3 / 4:

76.3%);

Anemia (G3 / 4: 9.2%);

thrombocytopenia

(G3 / 4: 5.2%)

Febrile neutropenia

Immune system disorders

Hypersensitivity (never severe)

Metabolism and nutrition disorders

Anorexia (G3 / 4: 0.6%)

Affection of the nervous system

Dysgeusia / parosmia; Peripheral sensory neuropathy (G3 / 4: 0.6%)

Fear of heights

Eye disorders

Increase of

watering

Conjunctivitis

Affections of the ear and labyrinth

Hearing disorders

Heart conditions

Myocardial ischemia (G3 / 4: 1.7%)

Arrhythmia (G3 / 4: 0.6%)

Vascular disorders

Venous disorders (G3 / 4: 0.6%)

Gastrointestinal disorders

Nausea (G3 / 4: 0.6%) Stomatitis (G3 / 4: 4.0%) Diarrhea (G3 / 4: 2.9%) Vomiting (G3 / 4: 0.6%)

Constipation Esophagitis / dysphagia / Odynophagia (G3 / 4: 0.6%)

Abdominal pain ; Dyspepsia

Gastrointestinal haemorrhage (G3 / 4: 0.6%)

Skin and subcutaneous tissue disorders

Alopecia (G3 / 4: 10.9%)

Rash with pruritus,

Dry Skin Desquamation (G3 / 4: 0.6%)

Musculoskeletal and systemic disorders

Myalgia (G3 / 4: 0.6%)

General disorders and administration site conditions

Lethargy (G3 / 4: 3.4%); Fever (G3 / 4: 0.6%); Fluid retention; Edema

investigations

Increase in weight

• Induction chemotherapy followed by chemoradiotherapy (TAX324)

MedDRA class-organ system

Very frequent effects

Frequent effects

Infrequent effects

Infections and infestations

Infection (G3 / 4: 3.6%)

Infection with neutropenia

Benign, malignant and unspecified tumors (including cysts and polyps)

Cancer pain (G3 / 4: 1.2%)

Blood and lymphatic system disorders

Neutropenia (G3 / 4: 83.5%); anemia (G3 / 4: 12.4); thrombocytopenia (G3 / 4: 4.0%); Febrile neutropenia

Affections of

system

immune

hypersensitivity

Metabolism and nutrition disorders

Anorexia (G3 / 4: 12.0%)

Nervous system disorders

Dysgeusia / parosmia (G3 / 4: 0.4%); Peripheral sensory neuropathy (G3 / 4: 1.2%)

Dizziness (G3 / 4: 2.0%);

Peripheral motor neuropathy (G3 / 4: 0.4%)

Eye disorders

Increased tearing

Conjunctivitis

Affections of the ear and labyrinth

Hearing Disorder (G3 / 4: 1.2%)

Heart conditions

Arrhythmia (G3 / 4: 2.0%)

Myocardial ischemia

Vascular disorders

Venous disorders

Gastrointestinal disorders

Nausea (G3 / 4: 13.9%);

Stomatitis (G3 / 4:

20.7%);

vomiting

(G3 / 4: 8.4%);

Diarrhea (G3 / 4: 6.8%);

Esophagitis / dysphagia /

odynophagia

(G3 / 4: 12.0%);

Constipation (G3 / 4:

0.4%)

Dyspepsia (G3 / 4: 0.8%);

Gastrointestinal pain (G3 / 4: 1.2%);

Gastrointestinal haemorrhage (G3 / 4: 0.4%)

Skin and subcutaneous tissue disorders

Alopecia (G3 / 4: 4.0%); Rash with pruritus;

Dry skin; peeling

Musculoskeletal and systemic disorders

Myalgia (G3 / 4: 0.4%)

General disorders and administration site conditions

Lethargy (G3 / 4: 4.0%); Fever (G3 / 4: 3.6%); Fluid retention (G3 / 4: 1.2%);

Edema (G3 / 4: 1.2%)

investigations

Weightloss

Increase in weight


Other adverse effects observed after the placing on the market

Benign and malignant tumors (including cysts and polyps)

Very rare cases of acute myeloid leukemia and myelodysplastic syndromes have been reported with docetaxel in combination with other antineoplastics and / or radiotherapy.

Blood and lymphatic system disorders

Myelosuppression and other hematologic adverse events have been reported. Cases of disseminated intravascular coagulation (DIC), often associated with sepsis or multiple organ failure, have been reported.

Immune system disorders

Some cases of sometimes fatal anaphylactic shocks have been reported.

Nervous system disorders

Rare cases of convulsion or transient loss of consciousness have been observed following administration of docetaxel. These reactions sometimes appear during the infusion of the drug.

Eye disorders

Very rare cases of transient visual disturbances (flashes, scintillations, scotomas) typically occurring during infusion of the product and in association with hypersensitivity reactions have been reported. These effects are reversible when the infusion is stopped. Rare cases of tearing, with or without conjunctivitis, and lacrimal duct obstruction with inadvertent tearing have been reported.

Affections of the ear and labyrinth

Rare cases of ototoxicity, hearing impairment and / or hearing loss have been reported.

Heart conditions

Rare cases of myocardial infarction have been reported.

Vascular disorders

Venous thromboembolic effects have been reported rarely.

Respiratory, thoracic and mediastinal disorders

Rare cases of acute respiratory distress syndrome, interstitial lung disease and pulmonary fibrosis have been reported rarely. Rare cases of radiation pneumonitis have been reported in patients receiving concomitant radiotherapy.

Gastrointestinal disorders

Rare cases of dehydration due to gastrointestinal events, intestinal perforations, ischemic colitis, colitis and enterocolitis during neutropenia have been reported. Rare cases of ileus and intestinal obstruction have been reported.

Hepatobiliary disorders

Very rare cases of sometimes fatal hepatitis have been reported, mainly in patients with pre-existing liver damage.

Skin and subcutaneous tissue disorders

Very rare cases of cutaneous lupus erythematosus and bullous eruptions such as erythema multiforme, Stevens-Johnson syndrome, Lyell syndrome, have been reported with docetaxel. In some cases, other concomitant factors may have contributed to the development of these effects. Cutaneous changes of the scleroderma type usually preceded by peripheral lymphoedema have been reported with docetaxel.

General disorders and administration site conditions

Radiation reaction reactivation phenomena have rarely been reported. Cases of fluid retention were not accompanied by acute episodes of oliguria or hypotension. Dehydration and pulmonary edema have been reported rarely.

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