On the part of the hematopoiesis system:
very often (≥ 10%) - reversible neutropenia (in patients who did not receive G-CSF), in a number of cases accompanied by fever, attachment of infections, and sometimes the development of sepsis and pneumonia. The number of neutrophils is reduced to the minimum values on average after 7 days (in patients who received previous chemotherapy, this period may be shorter), the average duration of severe neutropenia (<500 / μL) is also 7 days;
often (≥ 1 and <10%) - development of thrombocytopenia (platelet count <100000 / μl); bleeding, combined with thrombocytopenia (platelet count <50000 / μl) and anemia (hemoglobin <11 g / dL), including severe anemia (hemoglobin <8 g / dL).
From the immune system:
very often (≥ 10%) - mild or moderately sensitive hypersensitivity reactions usually occur within a few minutes after the onset of infusion (hot flashes, rashes, itching, chest tightness, back pain, dyspnea, drug fever, chills);
often (≥ 1 and <10%) - possible the development of severe reactions (lowering blood pressure, bronchospasm, generalized rash and erythema), which disappeared after discontinuation of infusion and the appointment of adequate therapy;
very rarely (<0.01%) - Lyell's syndrome, Stevens-Johnson syndrome.
From the skin and subcutaneous tissues:
very often (≥ 10%) - alopecia, mild and moderately expressed skin reactions;
rarely (≥0.01 and <0.1%) - a pronounced rash accompanied by itching, or limited erythema of the skin of the palms and feet with edema and subsequent desquamation, as well as edema of the hands, face and chest, hypo- or hyperpigmentation of the nails, onycholysis.
From the side of metabolism:
very often (≥ 10%) - fluid retention: cases of development of peripheral edema, pleural or pericardial effusion, ascites, weight gain. Peripheral edema usually appears on the lower limbs, and then can become generalized, resulting in an increase in body weight of 3 kg or more.The frequency and severity of fluid retention increases with repeated administration of the drug; the average total docetaxel dose at which fluid retention was observed was 818.9 mg / m3 during premedication2 and 489.7 mg / m2 - without premedication. However, in some cases, swelling occurred during the first course of therapy. The fluid retention was not accompanied by acute episodes of oliguria or arterial hypotension;
rarely (≥ 0.01 and <0.1%) - In rare cases, it was reported on the development of dehydration and pulmonary edema.
From the gastrointestinal tract:
very often (≥ 10%) - nausea, vomiting, diarrhea, anorexia, constipation, stomatitis, taste disorder, esophagitis, epigastric pain; Colitis, including ischemic, enterocolitis, perforation of the stomach or intestines;
often (≥ 1 and <10%) - for patients receiving monotherapy with docetaxel at a dose of 100 mg / m2, increased activity ACT, ALT, AFP, and serum bilirubin concentrations more than 2.5 times that of UHN are observed in less than 5% of cases;
infrequently (≥ 0.1 and <1%) - hepatitis (a lethal outcome was observed in patients with liver diseases in the anamnesis);
rarely (≥0.01 and <0.1%) - Gastrointestinal bleeding, intestinal obstruction.
From the side of the central nervous system and the peripheral nervous system:
Often (≥1%) - peripheral neuropathy in the form of easy or moderately expressed paresthesia, hyperesthesia, dysesthesia or pain, including burning. Motor disorders were characterized by muscle weakness. If these symptoms occur, dose adjustment is necessary. If symptoms persist, then treatment should be discontinued;
very rarely (<0.01%) - convulsions, transient loss of consciousness.
From the cardiovascular system:
often (≥ 1 and <10%) - heart rhythm disturbances (sinus tachycardia, atrial fibrillation), unstable angina, heart failure, decreased or increased blood pressure;
rarely (≥ 0.01 and <0.1%) - venous thromboembolism and myocardial infarction.
From the respiratory system:
very rarely (<0.01%) - acute respiratory distress syndrome and interstitial pneumonia, pulmonary fibrosis and increased reaction to irradiation.
From the musculoskeletal system:
often (≥ 1 and <10%) - arthralgia, myalgia, muscle weakness.
From the side of the organ of vision:
rarely (> 0.01 and <0.1%) - development of lacrimation in combined with conjunctivitis (or without it), transient visual impairment (flashes of light in the eyes, the appearance of cattle), usually occurring during the administration of the drug and combined with development of hypersensitivity reactions, which usually disappear after discontinuation of infusion;
very rarely (<0.01%), mainly in patients receiving other antitumoral drugs at the same time, the development of occlusion of the lacrimal canal, leading to excessive lacrimation.
Local reactions:
often (≥ 1 and <10%) - moderately expressed hyperpigmentation, inflammation, redness, dry skin, phlebitis, hemorrhage, edema of veins.
Other:
often (≥ 1 and <10%) - asthenia, dyspnea, generalized or local pain, including chest pain, not related to heart or lung disease.
When docetaxel is used in combination with doxorubicin In comparison with monotherapy with docetaxel, a high incidence of neutropenia was observed, including severe neutropenia; febrile neutropenia; thrombocytopenia, including severe thrombocytopenia; anemia; infections, including severe infections; nausea; vomiting; diarrhea, including severe diarrhea; constipation; stomatitis, including severe stomatitis; heart failure; alopecia; but a lower incidence of allergic reactions; skin reactions, including severe ones; defeat of nails,including heavy; fluid retention, including heavy; anorexia; neurosensory and neuromotor reactions, including severe forms; lowering blood pressure; heart rhythm disturbances; increased activity of "liver" transaminases, alkaline phosphatase, bilirubin concentration in the blood; myalgia; asthenia.
When docetaxel is used in combination with doxorubicin and cyclophosphamide (TAC scheme) compared with monotherapy with docetaxel, a lower incidence of neutropenia, severe anemia, febrile neutropenia, infections, allergic reactions,peripheral edema, neurosensory and neuromotor reactions, nail damage, diarrhea, anemia, but there was a high incidence of mild anemia, thrombocytopenia, nausea, vomiting, stomatitis, taste disorders, constipation, asthenia, arthralgia, alopecia. Colitis, enterocolitis, large intestine perforation without lethal outcomes were also observed (two of the four patients required discontinuation of treatment), acute myeloid leukemia / myelodysplastic syndrome. Prophylactic G-CSF reduced incidence of neutropenia (60%) and neutropenic infections 3-4 degrees.
When docetaxel is used in combinations with capecitabine there was more frequent development of undesirable phenomena from the gastrointestinal tract (stomatitis, diarrhea, vomiting, constipation, abdominal pain, eating disorders); arthralgia; severe thrombocytopenia and anemia; hyperbilirubinemia; palmar-plantar syndrome (hyperemia of the skin of the extremities / palms and feet / with subsequent edema and desquamation); but a more rare development of severe neutropenia; alopecia, disorders of the nails, including onycholysis; asthenia, myalgia, decreased appetite and anorexia. Dyspepsia, dry mouth, sore throat, candidiasis of the mouth, dermatitis, erythematous rash, discoloration of the nails, pyrexia, pain in the extremities, pain, back pain, lethargy (drowsiness, inhibition, stupor), swelling of the lower extremities shortness of breath , cough, nosebleeds, paresthesia, dizziness, headache, peripheral neuropathy, dehydration, lacrimation, weight loss. In patients over the age of 60 who received combination therapy with docetaxel and capecitabine, compared with patients of younger age, there is a more frequent development of toxicity of 3-4 degrees of severity.
In patients who received combined treatment with trastuzumab, a greater incidence of adverse reactions (nausea, diarrhea, constipation, abdominal pain, taste disorders, febrile neutropenia, arthralgia, anorexia) and a more frequent development of toxicity of 4 degrees of severity compared with monotherapy with docetaxel. There were cases of heart failure, especially when supplementing therapy with anthracyclines (doxorubicin or epirubicin).
When docetaxel is used according to the scheme AC TH (see the "Application and Dosage" section), the incidence of many side effects increased: alopecia, anemia, including anemia of 3-4 degrees of severity, nausea, including nausea of 3-4 degrees of severity, stomatitis, vomiting, diarrhea, constipation were more common , anorexia, abdominal pain, increased activity of ACT, ALT and alkaline phosphatase, myalgia, nail damage, arthralgia, 3-4 grade infections, heart failure. There was no increase in the frequency of neutropenia. Less commonly met neutropenia 3-4 degrees of severity, fluid retention, neurosensory and neuromotor reactions, rash and desquamation, allergic reactions.Insomnia was also observed, an increase in the concentration of creatinine in the blood.
When docetaxel is used in combination with cisplatin or carboplatin compared with monotherapy with docetaxel, thrombocytopenia appeared more often, including thrombocytopenia of 3-4 degrees of severity (mostly with carboplatin); nausea, including nausea 3-4 degrees of severity; diarrhea 3-4 degrees of severity; anorexia (mostly with cisplatin), including anorexia 3-4 degrees of severity; reaction at the site of administration. Less frequent neutropenia, including neutropenia 3-4 degrees of severity; anemia, including anemia of 3-4 degrees of severity, infections; febrile neutropenia; allergic reactions; skin reactions; defeat of nails; fluid retention, including fluid retention of 3-4 degrees of severity (mostly with carboplatin); stomatitis, neurosensory and, to a lesser extent, neuromotor neuropathy; alopecia and myalgia. Also observed: fever in the absence of infection, including 3-4 degrees of severity; pain.
When docetaxel is used in combination with prednisolone and prednisone Compared with monotherapy with docetaxel, the incidence of side effects was significantly reduced: anemia, including 3-4 degrees of severity; infections; neutropenia,including those of 3-4 degrees of severity; thrombocytopenia; febrile neutropenia; weakness; allergic reactions; neurosensory and neuromotor reactions; alopecia; rashes; desquamation; nausea, diarrhea; stomatitis; vomiting; anorexia; myalgia; arthralgia; fluid retention; but more often there were taste disorders and heart failure. Also observed: nasal bleeding, cough, shortness of breath, weakness, lacrimation.
When docetaxel is used in combination with cisplatin and fluorouracil In comparison with monotherapy with docetaxel, anemia was more frequent, including 3-4 degrees of severity; thrombocytopenia, including 3-4 degrees of severity; febrile neutropenia; neutropenic infections (even with the use of G-CSF); nausea, vomiting, anorexia, stomatitis, diarrhea, esophagitis / dysphagia / pain when swallowing; Infection was less common; allergic reactions; fluid retention; neurosensory and neuromotor reactions; myalgia; alopecia, rash, itching; defeat of nails, skin desquamation; disturbance of the rhythm of the heart. Also, fever was observed in the absence of infection; lethargy (drowsiness, confusion, numbness); changes in hearing; dizziness; lacrimation; dry skin; heartburn; myocardial ischemia; underlined venous pattern; cancer pain; decrease in body weight.Prophylactic use of G-CSF reduces the incidence of febrile neutropenia and / or neutropenic infections.
Data obtained during the application of the drug in the post-registration period
Benign, malignant and unspecified neoplasms (including cysts and polyps)
Rarely: acute myeloid leukemia and myelodysplastic syndrome associated with docetaxel, when used in combination with other chemotherapeutic agents and / or irradiation.
On the part of the hematopoiesis system
It has been reported that bone marrow hematopoiesis is suppressed and other hematological adverse reactions; development of the syndrome of disseminated intravascular coagulation (DVS-syndrome), often in combination with sepsis or multi-organ failure.
From the immune system
Rarely: anaphylactic shock, sometimes fatal. In patients who received premedication, the lethal outcome was very rare.
From the nervous system
Rarely: convulsions or transient loss consciousness, sometimes developing during intravenous infusion of the drug.
From the side of the organ of vision
Rarely: lacrimation in combination with conjunctivitis (or without it) and in very rare cases with obstruction of the tear duct, leading to its rupture; cases of transient visual disorders ("flashes of light in the eyes," the appearance of cattle), usually occurring during intravenous infusion administration of the drug and combined with the development of hypersensitivity reactions that usually disappeared after the cessation of intravenous infusion. Cases of cystic edema have been reported the macular area.
From the side of the hearing organ and labyrinthine disorders
Rarely: cases of ototoxic effect of the drug with hearing impairment and / or hearing loss, including cases associated with other ototoxic drugs.
From the side of the cardiovascular system
Rarely: venous thromboembolic complications and myocardial infarction
On the part of the respiratory system, the organs of the thorax and the mediastinum
Rarely: acute respiratory distress syndrome, interstitial pneumonia, interstitial lung disease, pulmonary fibrosis, respiratory failure, which could lead to death. With the simultaneous carrying out of irradiation, rare cases of radiation pneumonia.
From the gastrointestinal tract
Rarely: dehydration as a consequence development of reactions from the gastrointestinal tract; perforation of the stomach or intestines; colitis, including ischemic; neutropenic enterocolitis; rare cases of ileus (intestinal obstruction) and intestinal obstruction.
From the liver and biliary tract
Rarely: hepatitis, sometimes fatal, mainly in patients with concomitant liver disease.
From the skin and subcutaneous tissues
Rarely: cutaneous red lupus, bullous rash, erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis. It was reported about the development of such scleroderma changes, which preceded the peripheral lymphangiectatic edema. In some cases, the development of these phenomena caused co-infection, simultaneous use of other drugs and accompanying illnesses.
General disorders and disorders at the site of administration
Rarely: the phenomenon of the return of the local radiation reaction in the previously irradiated region, pulmonary edema.
From the side of the kidneys and urinary tract
Reported deterioration of kidney function and the development of renal failure, in most cases associated with the simultaneous use nephrotoxic drugs.
From the side of metabolism and nutrition
There have been reports of the development of cases of hyponatremia, mainly in combination with dehydration, vomiting and pneumonia.