Leukeran

Leukeran (chlorambucil) is an alkylating antineoplastic agent specifically formulated for the management of chronic lymphocytic leukemia (CLL) and certain types of non-Hodgkin lymphoma. As an oral chemotherapeutic drug belonging to the nitrogen mustard family, it works by cross-linking DNA strands, thereby inhibiting cancer cell replication and proliferation. Its well-established efficacy profile and oral administration make it a cornerstone in hematologic oncology, particularly for patients who may not be candidates for more aggressive treatment regimens. The drug represents a critical option in the therapeutic arsenal against indolent lymphoid malignancies.

Features

• Active ingredient: Chlorambucil (2mg tablets)
• Drug class: Nitrogen mustard alkylating agent
• Administration route: Oral
• Mechanism: Forms covalent bonds with DNA nucleobases
• Bioavailability: Approximately 70-90% after oral administration
• Half-life: 1.5 hours (terminal elimination)
• Metabolism: Hepatic via β-oxidation
• Excretion: Primarily renal (50-60% within 24 hours)

Benefits

• Provides targeted cytotoxic action against malignant lymphocytes while sparing some healthy cells
• Oral formulation enables convenient outpatient treatment and improved quality of life
• Demonstrated efficacy in achieving remission in previously untreated CLL patients
• Suitable for elderly patients or those with comorbidities who cannot tolerate aggressive chemotherapy
• Established safety profile with decades of clinical experience supporting its use
• Can be used as monotherapy or in combination regimens for various lymphoid malignancies

Common use

Leukeran is primarily indicated for the palliative treatment of chronic lymphocytic leukemia (CLL), with particular utility in older adult populations where more aggressive therapies may be contraindicated. It is also employed in the management of Hodgkin lymphoma and certain non-Hodgkin lymphomas, including Waldenström’s macroglobulinemia. The drug may be used as first-line therapy or as subsequent treatment following relapse. Clinical decisions regarding its use involve careful consideration of disease stage, patient age, performance status, and potential for bone marrow suppression. Treatment protocols typically involve intermittent courses rather than continuous administration to allow for hematopoietic recovery.

Dosage and direction

The recommended initial dosage for Leukeran is 0.1-0.2 mg/kg body weight daily (approximately 4-8 mg for a 70 kg adult) for 3-6 weeks. Alternatively, a intermittent regimen of 0.4 mg/kg may be administered in divided doses over 4 days, repeated every 2-4 weeks. Dosage must be individualized based on hematologic response and tolerance, with regular monitoring of complete blood counts. Tablets should be taken whole with water, preferably at the same time each day, with or without food. Treatment duration varies based on disease response and may continue for several months. Dose adjustments are mandatory for patients with renal impairment or those experiencing significant myelosuppression.

Precautions

Regular monitoring of complete blood counts is essential throughout therapy, with weekly assessments during initial treatment and regularly thereafter. Patients should be advised to report any signs of infection, unusual bleeding, or bruising immediately. Secondary malignancies, including acute myeloid leukemia, have been reported with long-term use. Leukeran may cause fetal harm and should not be used during pregnancy unless potential benefits outweigh risks. Adequate contraception is required for patients of reproductive potential. Vaccination with live vaccines should be avoided during treatment. Careful monitoring is required in patients with pre-existing bone marrow suppression or history of seizures.

Contraindications

Leukeran is contraindicated in patients with demonstrated hypersensitivity to chlorambucil or other alkylating agents. It should not be administered to patients with severe bone marrow suppression (unless the disease has infiltrated the bone marrow) or those who have demonstrated resistance to previous therapy with the drug. Use is contraindicated during pregnancy unless the potential benefit justifies the potential risk to the fetus. The drug is not recommended for patients with severe hepatic impairment without careful risk-benefit assessment. Concomitant administration with live vaccines is contraindicated.

Possible side effect

• Hematologic: Bone marrow suppression (anemia, leukopenia, thrombocytopenia), which may be severe and prolonged
• Gastrointestinal: Nausea, vomiting, diarrhea, oral ulceration, hepatotoxicity
• Dermatologic: Skin rash, urticaria, Stevens-Johnson syndrome (rare)
• Pulmonary: Pulmonary fibrosis and interstitial pneumonitis
• Neurological: Seizures (particularly at high doses), peripheral neuropathy
• Reproductive: Amenorrhea, oligospermia, azoospermia, infertility
• Other: Fever, allergic reactions, secondary malignancies, syndrome of inappropriate antidiuretic hormone secretion

Drug interaction

Leukeran exhibits significant interactions with other myelosuppressive agents, including other chemotherapy drugs and radiation therapy, potentially exacerbating bone marrow toxicity. Concurrent use with live vaccines may diminish vaccine efficacy and increase risk of infection. Drugs that affect hepatic metabolism may alter chlorambucil concentrations. Anticoagulants may have enhanced effects due to potential thrombocytopenia. Phenytoin and other anticonvulsants may require dosage adjustment. Nephrotoxic agents may reduce elimination and increase toxicity. Concomitant use with uricosuric agents may increase risk of hyperuricemia.

Missed dose

If a dose is missed, patients should take it as soon as remembered unless it is nearly time for the next scheduled dose. In such cases, the missed dose should be skipped, and the regular dosing schedule resumed. Patients should never double the dose to make up for a missed administration. Healthcare providers should be informed about any missed doses, as this may affect treatment monitoring schedules. Consistent adherence to the prescribed regimen is crucial for optimal therapeutic outcomes.

Overdose

Overdose with Leukeran primarily manifests as irreversible bone marrow suppression, including pancytopenia, with potentially fatal consequences. Gastrointestinal toxicity, including nausea, vomiting, and diarrhea, may occur. Neurological symptoms, including seizures, agitation, and ataxia, have been reported at high doses. There is no specific antidote for chlorambucil overdose. Management involves immediate discontinuation of the drug and supportive care, including transfusion of blood products, antimicrobial therapy for infections, and growth factor administration. Hemodialysis is not effective due to high protein binding. Hospitalization and intensive supportive care are required for suspected overdose.

Storage

Leukeran tablets should be stored at controlled room temperature (20-25°C or 68-77°F) in their original container, protected from light and moisture. The drug should be kept out of reach of children and pets. Unused medication should be disposed of properly through take-back programs or according to specific disposal instructions to prevent environmental contamination. Tablets should not be used beyond the expiration date printed on the packaging. Proper storage is essential to maintain drug stability and efficacy.

Disclaimer

This information is provided for educational purposes only and does not constitute medical advice. Treatment decisions must be made by qualified healthcare professionals based on individual patient circumstances. The prescribing physician should be consulted for complete information regarding indications, dosage, administration, and monitoring. Patients should not alter their treatment regimen without medical supervision. While every effort has been made to ensure accuracy, medical knowledge evolves, and current prescribing information should always be consulted.

Reviews

Clinical studies spanning decades have established Leukeran as an effective treatment for CLL, with response rates of 70-90% in previously untreated patients. The drug is particularly valued for its oral administration and manageable toxicity profile compared to more aggressive chemotherapeutic regimens. However, specialists note that its use has declined somewhat with the advent of targeted therapies, though it remains important for specific patient populations. Long-term follow-up studies indicate durable responses in many patients, though concerns about secondary malignancies with prolonged use persist. The medical community generally regards Leukeran as a valuable option in the hematologist’s armamentarium, especially for elderly patients or those with comorbidities.