Medicinal Products

DOCETAXEL KABI 180 mg / 9 ml 20 mg / 1 mL

Generic drug of the therapeutic class: Oncology and Hematology
active ingredients: Docetaxel
laboratory: Fresenius Kabi Oncology

Solution for solution for IV infusion
Box of 1 bottle of 9 ml
All forms

Indication

Breast cancer

DOCETAXEL KABI in combination with doxorubicin and cyclophosphamide is indicated for the adjuvant treatment of:

• operable breast cancer in patients with lymph node involvement • operable breast cancer in patients with no lymph node involvement

For patients with operable breast cancer without lymph node involvement, adjuvant therapy should be restricted to patients eligible for chemotherapy according to internationally established criteria for the initial treatment of early-stage breast cancer (see section 5.1 ).

DOCETAXEL KABI 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 KABI 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 KABI in combination with trastuzumab is indicated for the treatment of metastatic breast cancer with tumor over-expression of HER2, in patients not pre-treated with chemotherapy for metastatic disease.

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

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

Gastric cancer

DOCETAXEL KABI, 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 received chemotherapy for metastatic disease.

Cancer of the upper aero-digestive tract

DOCETAXEL KABI in combination with cisplatin and 5-fluorouracil is indicated for the induction therapy of locally advanced squamous cell carcinoma of the upper aero-digestive tract.

Dosage DOCETAXEL KABI 180 mg / 9 ml 20 mg / 1 mL Concentrate for solution for infusion IV Box of 1 vial of 9 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 or without lymph node 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 weeks. cycles (TAC scheme) (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 continuous 5-day infusion of fluorouracil is begun at a dosage of 750 mg / m² / day. The treatment is repeated every 3 weeks. Premedication with antiemetics 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 (VADS), the recommended dose of docetaxel is 75 mg / m 2 in 1 hour infusion, followed by cisplatin at 75 mg / mg. sqm infusion of 1 hour to D1, followed by 5 fluorouracil at the dosage of 750 mg / m² / day 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 aerodigestive tract (VADS) (unresectable technically, low probability of surgical curability or organ preservation), the recommended dose of docetaxel is 75 mg / day. m 2 intravenous infusion for 1 hour on D1, followed by cisplatin at the dosage of 100 mg / m 2 in 30 minutes infusion at 3 hours, followed by 5-fluorouracil 1000 mg / m 2 / 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 be given if the number of neutrophils is ≥ 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

Primary prophylaxis with G-CSF should be considered in patients receiving docetaxel, doxorubicin and cyclophosphamide (TAC) adjuvant therapy for breast cancer. Patients with febrile neutropenia and / or neutropenic infection should have a dose reduction of docetaxel to 60 mg / m² for all subsequent cycles (see Warnings and Precautions and Adverse Reactions sections).

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 the nadir in the number of platelets at the previous course of treatment was <25000 / mm 3, or with febrile neutropenia or severe toxicities 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, then resume treatment with 55 mg / m² docetaxel.

• 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 discontinued (see Warnings and Precautions ).

In case of toxicities, the dose adjustments of patients receiving docetaxel in combination with cisplatin and 5-fluorouracil (5-FU) are as follows:

Toxicity - grade

Dosage adjustments

Diarrhea - grade 3

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

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

Diarrhea - grade 4

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

2nd episode: discontinuation of treatment.

Stomatitis / mucitis -grade 3

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

2nd episode: definitive cessation of 5-FU only.

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

Stomatitis / mucitis -grade 4

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

2nd episode: 20% reduction in 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 with 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 ULN and higher alkaline phosphatase at 2.5 times the ULN, is 75 mg / m² (see Warnings and Precautions and Pharmacokinetic Properties sections ). In patients with bilirubinemia> ULN and / or ASAT and ALT 3.5 times ULN and alkaline phosphatase> 6x ULN, no dose reduction may be recommended and docetaxel should not be used. administered unless strictly indicated.

In the treatment of gastric adenocarcinoma, in combination with cisplatin and 5-fluorouracil, the pivotal study excluded patients with transaminase levels (ASAT and / or ALT)> 1.5 times the ULN associated with alkaline phosphatase> 2.5 times ULN and bilirubin> 1 times ULN: therefore, for these patients, no dose reduction may 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.

Pediatric populations

The safety and efficacy of DOCETAXEL KABI in nasopharyngeal carcinoma in children older than 1 month and less than 18 years is not yet established.

The use of DOCETAXEL KABI in pediatric populations in breast cancer, non-small cell lung cancer, prostate cancer, gastric cancer, cancer of the upper aerodigestive tract, not including nasopharyngeal cancers II and III poorly differentiated, is irrelevant.

Elderly patients:

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 listed in the Composition section.

Patients whose initial number of neutrophils is <1500 / mm 3 .

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 Kabi 180 MG / 9 ML

Summary of the tolerance profile for all indications

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). • 1276 patients (744 and 532 respectively in TAX 316 and GEICAM 9805) 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 were described using the NCI Common Criteria for Toxicity (grade 3 = G3, grade 3-4 = G3 / 4, grade 4 = G4) as well as COSTART and MEDRA 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); indeterminate frequency (can not be estimated based on available data).

Within each frequency group, adverse effects should be presented in order of decreasing 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 reactions (≥ 5%) in a phase III trial 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 usually 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 ).

Table of adverse effects for DOCETAXEL KABI 100 mg / m² monotherapy in breast cancer

MeDRA database of organ system classes

Very common

Frequent

Rare

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%)
Blood and lymphatic system disorders 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%); pains Reaction at the injection site; Chest pain of non-cardiac origin (severe: 0.4%)
investigations Elevation of bilirubin (G3 / 4 <5%); Elevation of alkaline phosphatases (G3 / 4 <4%); Elevation of ASAT (G3 / 4 <3%); ALT elevation (G3 / 4 <2%)

Description of some adverse effects in breast cancer for DOCETAXEL KABI 100 mg / m² monotherapy

Hematological 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 defects:

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 occurrence of moderate to severe fluid retention is delayed (median cumulative dose: 818.9 mg / m²) in premedicated patients 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.

Table of adverse effects for DOCETAXEL KABI 75 mg / m² monotherapy in breast cancer

MeDRA database of organ system classes

Very common

Frequent

Infections and infestations Infections (G3 / 4: 5%)
Blood and lymphatic system disorders Neutropenia (G4: 54.2%); Anemia (G3 / 4: 10.8%); Thrombocytopenia (G4: 1.7%) Febrile neutropenia
Immune system disorders Hypersensitivity (never 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; Cutaneous 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%); pains
investigations Elevation of bilirubin (G3 / 4 <2%)

Table of adverse effects for DOCETAXEL KABI 75 mg / m² in combination with doxorubicin in breast cancer

MeDRA database of organ system classes

Very common

Frequent

Rare

Infections and infestations Infection (G3 / 4: 7.8%)
Blood and lymphatic system disorders 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%); Fluid retention (severe: 1.2%); pains Injection site reactions
investigations Increased bilirubin (G3 / 4 < 2.5%); Increased alkaline phosphatase (G3 / 4 <2.5%) Increase of ASAT (G3 / 4 <1%); Increase in ALT (G3 / 4 <1%)

Table of adverse effects for DOCETAXEL KABI 75 mg / m² in combination with cisplatin

MeDRA database of organ system classes

Very common

Frequent

Rare

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%); Fluid retention (severe: 0.7%); Fever (G3 / 4: 1.2%) Injection site reactions pains
investigations Increased bilirubin (G3 / 4: 2.1%); Increase in ALAT (G3 / 4: 1.3%) Increase in ASAT (G3 / 4: 0.5%); Increased alkaline phosphatase (G3 / 4: 0.3%)

Table of adverse effects for DOCETAXEL KABI 100 mg / m² in combination with trastuzumab in breast cancer

MeDRA database of organ system classes

Very common

Frequent

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; Dyspnoea; 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

Description of some adverse effects in breast cancer for DOCETAXEL 100 mg / m² in combination with trastuzumab

Hematological and lymphatic system disorders:

Very common: Hematologic toxicity was higher in patients receiving trastuzumab and docetaxel than in patients receiving docetaxel alone (G 3/4 neutropenia: 32% vs. 22%, according to 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%).

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.

Table of adverse effects for DOCETAXEL KABI 75 mg / m² in combination with capecitabine in breast cancer

MeDRA database of organ system classes

Very common

Frequent

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
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; Erythematous rash (G3 / 4: <1%); Discoloration of the nails; Onycholysis (G3 / 4: 1%)
Musculoskeletal and systemic disorders Myalgia (G3 / 4: 2%); Arthralgia (G3 / 4: 1%) Extremity pain (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%)

Table of adverse effects for DOCETAXEL KABI 75 mg / m² in combination with prednisone or prednisolone in breast cancer

MeDRA database of organ system classes

Very common

Frequent

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; Nail Alteration (never severe) Eruption with desquamation (G3 / 4: 0.3%)
Musculoskeletal and systemic disorders Arthralgia (G3 / 4: 0.3%); myalgia
General disorders and administration site conditions Fatigue (G3 / 4: 3.9%); Fluid retention (severe: 0.6%)

Adjuvant therapy with DOCETAXEL KABI 75 mg / m² in combination with doxorubicin and cyclophosphamide in patients with node-positive breast cancer (TAX 316) and lymph node involvement (GEICAM 9805) - pooled data

MeDRA database of organ system classes

Very common

Frequent

Rare

Infections and infestations Infection (G3 / 4: 2.4%); Neutropenic infection (G3 / 4: 2.6%).
Blood and lymphatic system disorders Anemia (G3 / 4: 3%); Neutropenia (G3 / 4: 59.2%); Thrombocytopenia (G3 / 4: 1.6%); Febrile neutropenia (G3 / 4: not determined)
Immune system disorders Hypersensitivity (G3 / 4: 0.6%)
Metabolism and nutrition disorders Anorexia (G3 / 4: 1.5%)
Nervous system disorders Dysgeusia (G3 / 4: 0.6%); Peripheral sensory neuropathy (G3 / 4: <0.1%) Peripheral motor neuropathy (G3 / 4: 0%); Syncope (G3 / 4: 0%) Neurotoxicity (G3 / 4: 0%)
Eye disorders Conjunctivitis (G3 / 4: <0.1%) Lachrymation (G3 / 4: <0.1%);
Heart conditions Arrhythmia (G3 / 4: 0.2%);
Vascular disorders Vasodilation (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 Alopecia (G3 / 4: <0.1%); Dermal toxicity (G3 / 4: 0.6%); Nail Alteration (G3 / 4: 0.4%)
Musculoskeletal and systemic disorders Myalgia (G3 / 4: 0.7%); Arthralgia (G3 / 4: 0.2%)
Disorders of reproductive organs and breast Amenorrhea (G3 / 4: not determined);
General disorders and administration site conditions Asthenia (G3 / 4: 10.0%); Fever (G3 / 4: not determined); Peripheral edema (G3 / 4: 0.2%)
investigations Weight gain (G3 / 4: 0%) Weight loss (G3 / 4: 0.2%);

Description of some adverse effects for DOCETAXEL KABI 75 mg / m² in combination with doxorubicin and cyclophosphamide in patients with node-positive (TAX 316) and non-ganglionic breast cancer (GEICAM 9805)

Nervous system disorders:

In 84 patients with peripheral sensory neuropathy at the end of chemotherapy in the node-positive breast cancer (TAX316) study, neurosensory disorders persisted in 10 patients after follow-up.

Heart conditions:

In TAX316, 26 patients in the TAC arm (3.5%) and 17 patients in the FAC arm (2.3%) had congestive heart failure. Congestive heart failure was diagnosed in all patients, more than 30 days after the treatment period, with the exception of one patient in each arm. Two patients in the TAC arm and four patients in the FAC arm died from heart failure.

Skin and subcutaneous tissue disorders:

In study TAX316, persistent alopecia was reported during the follow-up period after the end of chemotherapy, in 687 TAC patients and 645 FCC patients. At the end of the follow-up period, alopecia persisted in 29 TAC patients (4.2%) and 16 FCC patients (2.4%).

Disorders of the reproductive organs and the breast:

In study TAX316, of 202 patients who had amenorrhea at the end of chemotherapy, amenorrhea persisted in 121 patients after follow-up.

General disorders and administration site defects:

In study TAX316, of the 119 patients with peripheral edema in the TAC arm, peripheral edema persisted in 19 patients and in 23 patients with peripheral edema in the FAC arm peripheral edema persisted. in 4 patients. In the GEICAM 9805 study, of the 5 patients who had lymphoedema at the end of chemotherapy, lymphedema persisted in 4 patients after follow-up.

Acute Leukemia / Myelodysplastic Syndrome

After a 10-year follow-up in the TAX316 study, acute leukemia was reported in 4 out of 744 TAC patients and 1 in 736 FCC patients. A myelodysplastic syndrome was reported in 2 out of 744 TAC patients and 1 in 736 FCC patients. .

After a median follow-up of 77 months, of 532 patients, one had acute leukemia in 532 patients (0.2%) who received the docetaxel, doxorubicin and cyclophosphamide combination in the GEICAM 9805 study. No cases were reported. reported in patients who received flurouracil, doxorubicin and cyclophosphamide. No myelodysplastic syndrome was diagnosed in one of the two treatment groups.

Neutropenic complications

The table below shows that the incidence of Grade 4 neutropenia, febrile neutropenia and neutropenic infections decreases in patients who received primary G-CSF prophylaxis after protocol amendment, making this prophylaxis mandatory in the TAC group -

GEICAM study.

Neutropenic complications in patients receiving the TAC protocol with or without primary G-CSF prophylaxis (GEICAM 9805).

Without primary prophylaxis by G-CSF

With primary prophylaxis by G-CSF

(N = 111)

(N = 421)

not(%)

not(%)

Neutropenia (Grade 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 2 (1, 8) 5 (1, 2)
(Grade 3-4)

Table of adverse effects for DOCETAXEL KABI 75 mg / m² in combination with cisplatin and 5-fluorouracil in gastric adenocarcinoma

MeDRA database of organ system classes

Very common

Frequent

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
System conditions Hypersensitivity (G3 / 4: 1.7%)
immune
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%)

Description of certain adverse effects in breast cancer for DOCETAXEL KABI 75 mg / m² in combination with cisplatin and 5-fluorouracil in gastric adenocarcinoma

Hematological 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 section Dosage and method of administration ).

Table of adverse effects in cancers of the upper aerodigestive tract for DOCETAXEL KABI 75 mg / m² in combination with cisplatin and 5-fluorouracil

• Induction chemotherapy followed by radiotherapy (TAX323)

MeDRA database of organ system classes

Very common

Frequent

Rare

Infections and infestations Infections (G3 / 4: 6.3%); Neutropenic infections
Benign and malignant tumors (including cysts and polyps) Cancer pain (G3 / 4: 0.6%)
Blood and lymphatic system disorders 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 Increased tearing 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)

MeDRA database of organ system classes

Very common

Frequent

Rare

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
Immune system disorders 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):

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

Hematological and lymphatic system disorders:

Myelosuppression and other hematologic adverse events have been reported. Cases of disseminated intravascular coagulation (CI

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