Leukeran

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Leukeran (chlorambucil) is a medication that is used to treat certain types of cancer (such as leukemia, lymphoma).

How does it work?

Chlorambucil has antitumor, alkylating, cytostatic, immunosuppressive effects. The substance binds to nucleoproteins of cell nuclei. It acts on DNA chains by alkylation through the formation of highly active ethyleneimonium radicals, causes cross-linking or breaking of DNA strands and disrupts their replication. It has a toxic effect on both dividing and non-dividing cells. It depresses tumor and hematopoietic tissue. It acts more selectively on lymphoid tissue than on granulocytic elements. The clinical effect is manifested after 3-4 weeks. In some patients, during the first 2 years of treatment, the total number of blood leukocytes normalizes, the relative content of lymphocytes in the bone marrow is 20%, splenomegaly is eliminated and enlarged lymph nodes are reduced.

Indications

Hodgkin’s disease;
some forms of non-Hodgkin lymphoma;
chronic lymphocytic leukemia;
Waldenstrom macroglobulinemia.

Dosage and administration

The drug is taken orally.

The standard dose for Hodgkin’s disease is 0.2 mg/kg/day for 4-8 weeks. The standard dose for non-Hodgkin’s lymphoma is 0.1-0.2 mg/kg/day for 4-8 weeks, maintenance treatment is carried out by reducing the daily dose or intermittent courses of treatment.

The standard dose for chronic lymphocytic leukemia is 0.15 mg/kg/day (until the white blood cell count drops to 10,000 per mm3). Therapy can be resumed four weeks after the end of the first course with the subsequent dose of 0.1 mg/kg/day.

The standard dose for Waldenstrom macroglobulinemia is 6-12 mg/day until leukopenia occurs, then therapy is continued at a dose of 2-8 mg/day for an indefinite time.

Side effects

Hemopoietic system: frequent – leukopenia (reversible if the drug is stopped in a timely manner), thrombocytopenia, lymphopenia, neutropenia, decreased hemoglobin content; extremely rare – irreversible inhibition of bone marrow function;
Gastrointestinal tract: frequent – nausea, vomiting, diarrhea, ulceration of the oral mucosa; rare – hepatotoxic effect of toxic allergic genesis (hepatonecrosis or cirrhosis, cholestasis, jaundice);
Respiratory system: extremely rare – interstitial pulmonary fibrosis (with prolonged use of chlorambucil), interstitial pneumonia;
Allergic reactions: rare – skin rash, angioedema; extremely rare – erythema multiforme exudative (Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome);
Nervous system: frequent – convulsions in children with nephrotic syndrome; rare – local and / or generalized convulsions in children and adults receiving chlorambucil in therapeutic doses daily or courses of high-dose pulse therapy; extremely rare – insecurity when walking, tremors, muscle twitches, peripheral neuropathy, paresis, agitation, confusion, severe weakness, anxiety, hallucinations;
Urinary system: extremely rare – aseptic cystitis;
Other: drug hyperthermia, hyperuricemia or nephropathy due to increased formation of uric acid (the result of rapid cell breakdown), menstrual irregularities, secondary amenorrhea, azoospermia, secondary malignancy.

Contraindications

Leukeran is not used in the following cases:

hypersensitivity to chlorambucil and other alkylating drugs;
bone marrow hypoplasia (severe leukopenia, thrombocytopenia);
epilepsy;
renal failure;
severe liver dysfunction.

Overdose

Symptoms: reversible pancytopenia, increased irritability, ataxia, repeated epileptoid seizures. The specific antidote is not known.

Treatment: immediate gastric lavage, monitoring and maintaining vital functions of the body, close monitoring of blood tests and general supportive measures, including transfusion of blood or its components according to indications. Dialysis is not effective.

Interaction with other drugs

The simultaneous use with drugs that inhibit hematopoiesis may cause an increased myelotoxicity;
When this drug is used together with antigout agents, dose adjustment of the latter is required (chlorambucil may increase the concentration of uric acid in the blood);
Tricyclic antidepressants, as well as haloperidol, maprotiline, monoamine oxidase inhibitors, phenothiazines, thioxanthenes, can lower the threshold for seizure activity and increase the risk of seizures;
Drugs that bind to plasma proteins intensely increase the toxicity of chlorambucil (competition at the level of protein binding);
The simultaneous use with inactivated viral vaccines can cause a reduced antibody production in response to vaccine administration; the joint use with live viral vaccines can cause intensification of the process of replication of the vaccine virus, increasing its adverse effects and/or reducing the production of antibodies.

Pregnancy and breastfeeding

The use of Leukeran during pregnancy, especially in the first trimester, should be avoided.

Reliable contraceptives should be used during the period of treatment.

If the drug should be used during lactation, breastfeeding is stopped.

Precautions

The drug is used with caution in the following conditions (it is necessary to compare risk and benefit): inhibition of bone marrow function (severe leukopenia, thrombocytopenia and anemia); chickenpox (currently or recently transferred), herpes zoster, acute infectious diseases of a viral, fungal and bacterial nature, bone marrow infiltration by tumor cells, gout (history), urate nephrolithiasis, head injury (history), epilepsy (history), severe liver and kidney disease.

When used in therapeutic doses, Leukeran inhibits the production of lymphocytes and to a lesser extent affects the number of neutrophils and platelets, as well as the level of hemoglobin. There is no need to stop taking the tablets at the first sign of a decrease in the number of neutrophils, however, you should remember that the decrease in the number of neutrophils can continue for 10 or more days after taking the last dose.

The medicine should not be prescribed to patients who have recently undergone radiation therapy, or who received treatment with cytostatic drugs.

In case of lymphocytic bone marrow infiltration or in case of bone marrow hypoplasia, the daily dose of the drug should not exceed 0.1 mg/kg body weight.

Children with nephrotic syndrome, patients receiving high-dose pulse therapy with Leukeran, as well as patients with a history of seizures, should be closely monitored during the course of treatment, as they may be at increased risk of developing seizures.

Chlorambucil can cause chromatid or chromosomal damage in humans and is carcinogenic in animals. The possibility of such an effect should be considered when planning a long-term treatment.

The occurrence of acute secondary hemoblastoses (including leukemia and myelodysplastic syndrome) has been reported, especially after prolonged treatment.

When comparing patients with ovarian cancer who received and did not receive alkylating cytostatic drugs, it was revealed that the use of alkylating cytostatic drugs, including chlorambucil, significantly increased the incidence of acute leukemia.

A small number of cases of acute myeloid leukemia have been reported in patients receiving chlorambucil as long-term adjuvant therapy for breast cancer. When considering the use of chlorambucil, it is necessary to assess the ratio of the risk of developing leukemia to the potential therapeutic benefit.

Studies of the impact on the ability to drive a car and control mechanisms have not been conducted.