The incidence of adverse reactions listed below is set out according to the following gradation: very often (≥ 1/10), often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rarely (<1/10000), the frequency is unknown (can not be determined on the basis of available data).
Violations of the blood and lymphatic system
Often: oppression of bone marrow hematopoiesis, thrombocytopenia, leukopenia, anemia.
Benign, malignant and unspecified neoplasms (including cysts and polyps)
Frequency unknown: reported the development of acute leukemia and bone marrow dysplasia in patients who had received nitrosourea preparations for a long time.
Disorders from the gastrointestinal tract
Often: nausea, vomiting, anorexia.
Rarely: diarrhea, stomatitis.
Disturbances from the liver and bile ducts
Often: violation of liver function (in most cases, mild degree of severity).
Rarely: cholestatic jaundice, hepatic insufficiency.
Disturbances from the respiratory system, chest and mediastinal organs
Rarely: interstitial pneumonia, infiltrative processes, pulmonary fibrosis.
Disturbances from the nervous system
Rarely: impaired coordination, confusion, drowsiness, apathy, speech articulation disorder, stuttering (reported on development of these symptoms in combination therapy with other antitumor agents and radiation therapy).
Disorders from the nochek and urinary tract
Frequency unknown: renal failure, progressive azotemia, decrease in the size (atrophy) of the kidneys.
Disorders from the rut and subcutaneous tissues
Rarely: alopecia.
Disturbances on the part of the organ of sight
Rarely: defeat of the optic nerves (when combined with radiation therapy of brain tumors), irreversible loss of vision.
Impact on the results of laboratory and instrumental studies
Frequency unknown: increased activity of hepatic enzymes (aspartate aminotransferase (ACT), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase), increased serum bilirubin concentration.
The main undesirable side effect of lomustine is delayed or prolonged myelotoxicity, which usually manifests itself 4-6 weeks after taking the drug and is dose-dependent. Thrombocytopenia occurs approximately 4 weeks after taking a dose of lomustine and is usually stored on level of 80000 - 100000 / μL for 1-2 weeks. After 5-6 weeks, there is leukopenia (about 4000 - 5000 / μl), which persists for one or two weeks. Anemia is less common, however, compared with thrombocytopenia and leukopenia, it is less common and occurs in a less severe form.
Hematologic toxicity can be cumulative, and after receiving repeated doses, there may be more pronounced suppression of bone marrow function. Approximately 65% of patients receiving the drug at a dose of 130 mg / m2, the concentration of leukocytes decreased to levels less than 5000 / μl.In 36% of patients this figure was less than 3000 / μL. As a rule, thrombocytopenia is more severe than leukopenia; however, both types of toxicity may be dose-limiting.
Nausea and vomiting usually appear 4-6 hours after the administration of a full single dose of lomustine and last 24-48 hours, anorexia usually lasts for 2-3 days. The severity of these side effects can be reduced by dividing the single dose, calculated for 6 weeks, the sodium intake in the first three days of each 6-week cycle. Usually the drug is well tolerated if its use is accompanied by a prophylactic intake of antiemetics (for example, metoclopramide or chlorpromazine).
In isolated cases, after prolonged treatment with lomustine and other preparations of nitrosourea, when a high cumulative dose was reached, renal failure, progressive azotemia, diminishing the size (atrophy) of the kidneys were observed. In this regard, it is recommended not to exceed the maximum total cumulative dose of lomustine 1000 mg / m2. However, it must be borne in mind that kidney damage is also possible in patients who received lower cumulative doses of the drug.