The safety of the Jevtan preparation in combination with prednisolone was evaluated in 371 patients with metastatic castration-resistant prostate cancer. Median of patients' cycles of Jevtan's preparation® was 6 cycles.
Very frequent (≥ 10%) adverse reactions (HP) of all degrees of severity were anemia, leukopenia, neutropenia, thrombocytopenia, diarrhea, fatigue, nausea, vomiting, constipation, asthenia, abdominal pain, hematuria, back pain, arthralgia, anorexia, peripheral neuropathy (including peripheral sensory and motor neuropathies), pyrexia, dyspnea, dysgeusia, cough, alopecia.
Frequently encountered (≥ 5%) HP ≥3 degrees of severity with the use of Jevtan® was neutropenia, leukopenia, anemia, febrile neutropenia, diarrhea, fatigue and asthenia.
The termination of treatment due to the development of HP occurred in 18.3% of patients treated with Jevtan®. The most common HP, leading to discontinuation of treatment with Jevtan®, was neutropenia and kidney failure.
The most frequent HP, leading to death in patients treated with Jevtan®, had infections. Most adverse reactions in the form of fatal infections developed after a single injection of Jevtan®.
Below are the HP, divided according to the system-organ classes according to the classification of the Medical dictionary for normative-legal activity (MedDRA). Heaviness HP was classified in accordance with generally accepted terminology criteria for HP (HSSAE 4.0) (severity ≥ 3 = G ≥ 3).
Classification of frequency of occurrence HP World Health Organization: very often (≥ 10%); often (≥ 1% and <10%); infrequently (≥ 0.1% and <1%); rarely (≥0.01% and <0.1%); very rarely (<0.01%); unknown frequency (according to available data, determine frequency of occurrence HP does not seem possible).
Within each group by frequency of occurrence HP, the latter are given in order of decreasing their severity.
Infectious and parasitic diseases
Often: septic shock (all cases ≥ 3 degrees of severity); sepsis (all cases ≥ 3 degrees of severity); inflammation of subcutaneous fat, urinary tract infections of all severity; flu; cystitis; upper respiratory tract infection; infections caused by Varicella zoster (herpes zoster); candidiasis.
Infrequently: inflammation of subcutaneous fat ≥ 3 degrees of severity, cystitis ≥ 3 degrees of severity.
Blood disorders and lof the imphatic system
Very often: neutropenia of all severity levels, including neutropenia with clinical manifestations ≥3 degrees of severity; anemia of all severity; leukopenia of all degrees of severity; thrombocytopenia.
Often: febrile neutropenia, all cases ≥ 3 degrees of severity, thrombocytopenia ≥ 3 degrees of severity.
Neutropenic complications included neutropenic infection, neutropenic sepsis, and septic shock, which in some cases resulted in death.
It has been shown that the use of G-CSF reduces the incidence and severity of neutropenia (see the sections "Dosing and Administration" and "Special instructions").
Immune system disorders
Often: hypersensitivity reactions, including severe reactions, such as generalized rash / erythema, decreased blood pressure and bronchospasm.
Metabolic disorders
Often: anorexia.
Often: dehydration of all degrees of severity, hyperglycemia, hypokalemia.
Infrequently: anorexia ≥ 3 degrees of severity, hyperglycemia ≥ 3 degrees of severity, hypokalemia ≥ 3 degrees of severity.
Disorders of the psyche
Often: anxiety, confusion.
Disturbances from the nervous system
Often: dysgeusia (perversion of taste).
Often: peripheral neuropathy: peripheral sensory neuropathy (paresthesia, dysesthesia, hypoesthesia) and peripheral motor neuropathy; dizziness, headache, lethargy, sciatica.
Infrequently: peripheral neuropathy ≥ 3 degrees of severity; peripheral sensory neuropathy ≥ 3 degrees of severity, lethargy ≥ 3 degrees of severity, sciatica ≥3 degrees of severity.
Disturbances on the part of the organ of sight
Often: conjunctivitis, increased tearing.
Hearing disorders and labyrinthine disorders
Often: ringing in the ears, vertigo (feeling of deflection or twisting of one's own body or surrounding objects).
Heart Disease
Often: atrial fibrillation (atrial fibrillation), tachycardia (no cases of tachycardia ≥ 3 degrees of severity).
Infrequently: atrial fibrillation (atrial fibrillation) ≥ 3 degrees of severity.
When taking cabazitaxel, there were cases of developing heart failure (in two patients). One patient in the cabazitaxel group died of heart failure. Fatal ventricular fibrillation was observed in 1 patient and heart failure in 2 patients. However, none of these cases was regarded by researchers as related to the use of cabazitaxel.
Vascular disorders
Often: reduction of blood pressure, deep vein thrombosis of all severity, increased blood pressure, orthostatic hypotension, "hot flashes" of blood to the face skin with a feeling of heat, hyperemia.
Infrequently: a decrease in blood pressure ≥ 3 degrees of severity, an increase in blood pressure ≥ 3 degrees of severity, orthostatic hypotension ≥ 3 degrees of severity.
Disturbances from the respiratory system, organs of the chest and mediastinum
Often: shortness of breath, cough.
Often: shortness of breath ≥ 3 degrees of severity, pain in the mouth and pharynx, pneumonia of all degrees of severity.
There have been cases of interstitial pneumonia / pneumonitis, interstitial lung disease, acute respiratory distress syndrome, including fatal.
Disorders from the gastrointestinal tract
Very often: diarrhea, nausea, vomiting, constipation, abdominal pain.
Often: diarrhea ≥ 3 degrees of severity, nausea ≥ 3 degrees of severity, vomiting ≥ 3 degrees of severity, constipation ≥ 3 degrees of severity, abdominal pain ≥ 3 degrees of severity, dyspepsia, epigastric pain, hemorrhoids, gastroesophageal reflux disease, rectal bleeding, dryness of the oral mucosa , bloating.
Infrequently: bleeding from the rectum ≥ 3 degrees of severity, dryness of the oral mucosa ≥ 3 degrees of severity, bloating ≥ 3 degrees of severity.
Unknown frequency: reported on the development of colitis, enterocolitis, gastritis, neutropenic enterocolitis, gastrointestinal bleeding and perforation of the gastrointestinal tract, intestinal obstruction and intestinal obstruction.
Disturbances from the skin and subcutaneous tissues
Often: alopecia.
Often: dry skin, erythema.
Disturbances from musculoskeletal and connective tissue
Often: pain in the spine, arthralgia.
Often: pain in the spine ≥ 3 degrees of severity, arthralgia ≥ 3 degrees of severity, pain in the extremities of all degrees of severity, muscle spasms, myalgia, musculoskeletal pain in the thoracic region, pain along the lateral surfaces of the trunk.
Infrequently: myalgia ≥ 3 degrees of severity, musculoskeletal pain in the thoracic region ≥ 3 degrees of severity, pain along the lateral surfaces of the trunk ≥ 3 degrees of severity.
Disorders from the kidneys and urinary tract
Often: hematuria of all severity levels (in 2/3 cases, weighting factors such as disease progression, instrumental interventions, concomitant infections, simultaneous administration of anticoagulants, non-steroidal anti-inflammatory drugs, acetylsalicylic acid) were determined.
Often: acute renal sufficiency of all degrees of severity; renal insufficiency of all degrees of severity; dysuria; renal colic; hematuria ≥ 3 degrees of severity; pollakiuria; hydronephrosis; retention of urine; urinary incontinence; obstruction of the ureters of all degrees of severity.
Infrequently: renal colic ≥ 3 degrees of severity, pollakiuria ≥ 3 degrees of severity, hydronephrosis ≥ 3 degrees of severity, urinary retention ≥ 3 degrees of severity.
Violations of the genitals and mammary gland
Often: pain in the pelvic area.
Infrequently: pain in the pelvic area ≥ 3 degrees of severity.
General disorders and disorders at the site of administration
Often: increased fatigue, asthenia, pyrexia.
Often: increased fatigue ≥ 3 degrees of severity; asthenia ≥ 3 degrees of severity; pyrexia ≥ 3 degrees of severity; peripheral edema; inflammation of the mucous membranes; pain of all degrees of severity; pain in the chest; edema; chills; malaise.
Infrequently: peripheral edema ≥ 3 degrees of severity, inflammation of the mucous membranes ≥ 3 degrees of severity, chest pain ≥ 3 degrees of severity, edema ≥ 3 degrees of severity.
Laboratory and instrumental data
Often: decrease in body weight, increased activity of ALT in the blood serum.
Infrequently: increased serum bilirubin concentration, increased activity ACT in the blood serum.
HP in special patient groups
Elderly patients
Of the 371 patients,who received treatment with Jevtan® in a study on treatment of prostate cancer, 240 patients were 65 years of age or older, 70 of them older than 75 years of age.
The following HP met witha ≥ 5% is more likely in patients aged 65 years and older than younger patients: increased fatigue, neutropenia with clinical manifestations, asthenia, pyrexia, dizziness, urinary tract infections and dehydration.
Frequency of the following HP ≥3 degrees of severity was higher in patients ≥65 years of age compared with younger patients: neutropenia from laboratory tests, neutropenia with clinical manifestations, and febrile neutropenia.
Of the 595 patients treated with Jevtan® in the study EFC11785 for the treatment of prostate cancer, 420 patients were 65 years of age or older.
The following HP met at ≥ 5% is more likely in patients aged 65 years and older compared with younger patients: diarrhea, fatigue, asthenia, constipation, neutropenia with clinical manifestations, febrile neutropenia, dyspnea.