The newly diagnosed multiform glioblastoma (adult patients)
Below are the side effects noted in the treatment of patients with newly diagnosed multiform glioblastoma during the combined and adjuvant phases of treatment in clinical trials. Side effects are presented for organs and systems according to the frequency of their occurrence according to the recommendations of the World Health Organization: very often (> 10%), often (> 1% to <10%), infrequently (>> 0.1% to < 1), rarely (> 0.01% and <0.1%), very rarely (<0.01%).
Combined phase of treatment (with radiotherapy)
Infectious and parasitic diseases: often - candidiasis of the oral cavity, Herpes simplex, pharyngitis, wound infection, other infections;
Violations from the blood and lymphatic system: often - leukopenia, lymphopenia, neutropenia, thrombocytopenia; infrequently - anemia, febrile neutropenia; Disorders from the endocrine system: infrequently - cushingoid;
Disorders from the metabolism and nutrition: very often - anorexia; often hyperglycemia, weight loss; infrequently - hypokalemia, weight gain; Disorders of the psyche: often - anxiety, emotional lability, insomnia; infrequently - agitation, apathy, behavioral disorders, depression, hallucinations; Impaired nervous system: very often - headache; often - dizziness, aphasia, balance disorder, confusion and decreased consciousness, convulsions, memory impairment, neuropathy, paresthesia, drowsiness, speech disorder, impaired concentration, tremor; infrequent - extrapyramidal disorders, dysphasia, ataxia, impaired perception, gait disorders, hemiparesis, hyperesthesia, hypoesthesia, neurological disorders (unspecified), epileptic status, parosmia, thirst;
Disorders from the side of the organ of vision: often - blurred vision; infrequently - pain in the eye, hemianopsia, impaired vision, reduced visual acuity, limiting visual fields;
Hearing disorders and labyrinthine disturbances: often - hearing impairment, infrequently - earache, hyperacusis, otitis media, tinnitus;
Heart Disease: infrequent - palpitation;
Vascular disorders: often - swelling, including edema pog, hemorrhage; infrequently - increased blood pressure, cerebral hemorrhage;
Disturbances from the respiratory system, chest and mediastinal organs often - cough, shortness of breath; infrequently - pneumonia, infections of the upper respiratory tract, nasal congestion;
Violations from the e / seludo-intestinal tract: very often - constipation, nausea, vomiting; often - abdominal pain, diarrhea, dyspepsia, dysphagia, stomatitis, a taste disorder; infrequently - changing the color of the tongue;
Disorders from the liver and bile ducts: often - increased activity of alanine aminotransferase (ALT); infrequently, an increase in the activity of alkaline phosphatase (APF), gamma-glutamyl transferase (GGT), aspartate aminotransferase (ACT), liver enzymes;
Disturbances from the skin and subcutaneous tissues: very often - alopecia, rash; often - dermatitis, dry skin, erythema, itchy skin; infrequently - photosensitivity reactions, pigmentation disorders, exfoliation;
Disturbances from the musculoskeletal and connective tissue: often - arthralgia, muscle weakness; infrequently - back pain, musculoskeletal pain, myalgia, myopathy;
Disorders from the kidneys and urinary tract: often - frequent urination, urinary incontinence;
Violations of the genitals and breast: infrequently - impotence; General disorders and disorders at the site of administration: very often fatigue; often - fever, pain syndrome, radiation damage, allergic reaction, edema of the face; infrequently - "hot flashes" of heat to the body, asthenia, worsening of the condition, chills.
Adjuvant phase of treatment
Infectious and parasitic diseases: often - candidiasis of the oral cavity, other infections; infrequently - Herpes simplex, Herpes zoster, influenza-like syndrome;
Violations from the blood and lymphatic system: often - anemia, febrile neutropenia, leukopenia, thrombocytopenia; infrequently - lymphopenia, petechiae;
Disorders from the endocrine system; infrequently - cushingoid;
Disorders from the metabolism and nutrition; very often - anorexia; often - a decrease in body weight; infrequently hyperglycemia, weight gain;
Disorders of the psyche: often - anxiety, depression, emotional lability, insomnia; infrequently - hallucinations, amnesia;
Impaired nervous system: very often - headache, convulsions; often - dizziness, aphasia, imbalance, confusion, dysphasia, speech disorder, hemiparesis, memory impairment, impaired concentration, neurological disorders (unspecified), neuropathy, peripheral neuropathy, paresthesia, drowsiness, tremor; infrequent - gait disturbance, ataxia, coordination disorder, hemiplegia, hyperesthesia, sensitivity disorders;
Disorders from the side of the organ of vision: often - blurred vision, diplopia, limitation of visual fields; infrequently - pain in the eye, dry eyes, decreased visual acuity;
Hearing disorders and labyrinthine disturbances: often - hearing impairment, ringing in the ears, infrequently - deafness, pain in the ear, vertigo;
Vascular disorders: often - swelling of the legs, hemorrhage, deep vein thrombosis;
infrequently - edema, including peripheral edema, pulmonary embolism; Disturbances from the respiratory system, chest and mediastinal organs: often - cough, shortness of breath; infrequently - pneumonia, infection of the upper respiratory tract, sinusitis, bronchitis; Disorders from the gastrointestinal tract: very often - anorexia constipation, nausea, vomiting; often - diarrhea, dyspepsia, dysphagia, stomatitis, dry mouth, perversion of taste; infrequent abdominal distention, fecal incontinence, hemorrhoids, gastroenteritis, dental diseases, gastrointestinal disorders (unspecified); Disorders from the liver and e / selchevyvodayuschih ways: often - increased ALT activity;
Disturbances from the skin and subcutaneous tissues: very often - alopecia, rash; often - dry skin, itchy skin; infrequently - erythema, a violation of pigmentation, increased sweating;
Disturbances from the musculoskeletal and connective tissue: often - arthralgia, muscle weakness, myalgia, musculo-skeletal pains, infrequently - back pain, myopathy;
Disorders from the kidneys and urinary tract: often - urinary incontinence; infrequently - dysuria;
Violations of the genitals and milk e / seleza: infrequently - pain in the breast, amenorrhea, menorrhagia, vaginal bleeding, vaginitis;
General disorders and disorders at the site of administration: very often fatigue; often - fever, pain syndrome, radiation damage, allergic reaction; infrequently - asthenia, edema of the face, worsening of the condition, chills.
Laboratory and instrumental data: Myelosuppression (neutropenia and thrombocytopenia), is a dose-limiting side effect. Among patients in both groups (combined and adjuvant therapy), neutrophil changes, including neutropenia, were noted in 8% of cases, and platelet counts, including thrombocytopenia, in 14% of cases.
Progressive or recurrent malignant glioma (adults and children over 3 years old) or malignant melanoma (adults)
Side effects are presented for organs and systems according to the frequency of their occurrence according to the recommendations of the World Health Organization: very often (> 10%), often (> 1% to <10%), infrequently (>> 0.1% to < 1), rarely (> 0.01% and <0.1%), very rarely (<0.01%):
Infectious and parasitic diseases: rarely opportunistic infections, including pneumocystis pneumonia;
Violations from the blood and lymphatic system: Often - thrombocytopenia, neutropenia, lymphopenia; often - pancytopenia, leukopenia, anemia. In patients with glioma and metastatic melanoma, thrombocytopenia and grade 3 or 4 neutropenia were observed in 19% and 17%, respectively, in glioma and in 20% and 22%, respectively, in melanoma.Hospitalization of patients was required in this case in 8% and 4% of cases, respectively, with glioma and in 3% and 1.3% with melanoma. Oppression of the bone marrow developed during the first few cycles of treatment, with a maximum between 21 and 28 days; recovery occurred, usually within 1-2 weeks. No evidence of cumulative myelosuppression was noted. The presence of thrombocytopenia could increase the risk of bleeding, and the presence of neutropenia or leukopenia increased the risk of infectious complications.
Disorders from the metabolism and nutrition: very often - anorexia; often - weight loss;
Impaired nervous system: very often - headache; often - drowsiness, dizziness, paresthesia, peripheral neuropathy;
Disturbances from the respiratory system, chest and mediastinal organs: often shortness of breath;
Disorders from the gastrointestinal tract: very often - nausea, vomiting, constipation; often - diarrhea, abdominal pain, indigestion, taste perversion. The most frequent were nausea and vomiting. In most cases, these phenomena were 1-2 (from mild to moderate) severity and passed independently or were easily controlled with standard therapy. The incidence of severe nausea and vomiting was 4%. Disturbances from the skin and subcutaneous tissues: often - rash, itching, alopecia, petechiae; very rarely - hives, exanthema, erythroderma, erythema multiforme;
General disorders and disorders at the site of administration: very often - increased fatigue; often - fever, chills, general malaise, asthenia, pain syndrome; very rarely - allergic reactions, including anaphylaxis, angioedema;
Laboratory and instrumental data: cases of thrombocytopenia and neutropenia of grade 3 or 4 in 19% and 17%, respectively, in glioma and in 20% and 22% in melanoma, respectively, were observed in the treatment of patients with glioma and metastatic melanoma. Hospitalization of the patient and / or removal of temozolomide was required in 8% and 4% of cases, respectively, for glioma and 3% and 1.3% for melanoma. Myelosuppression progressed predictably, usually during the first few treatment cycles, with a maximum between 21 and 28 days; recovery occurred quickly, usually within 1-2 weeks. No evidence of cumulative myelosuppression was noted. The presence of thrombocytopenia could increase the risk of bleeding, and the presence of neutropenia or leukopenia increased the risk of infectious complications.
Post-registration research data
During postemergence studies of temozolomide, erythema multiforme, toxic epidermal necrolysis, Stevens-Johnson syndrome, and allergic reactions, including anaphylaxis, were very rare.
Hepatotoxicity has been reported with an increase in hepatic enzyme activity, hyperbilirubinemia, cholestasis, hepatitis with hepatic impairment, including fatal cases.
Opportunistic infections were rare, including pneumonia caused by Pneumocystis carinii; Very rarely reported cases of interstitial pneumonitis / pneumonitis, pulmonary fibrosis and fatal respiratory failure. Also, very rarely was the development of myelodysplastic syndrome (MDS) and secondary malignant processes, including leukemia; very rarely met the development of prolonged pancytopenia in several cases - with the development of lethal aplastic anemia.