Leukeran (chlorambucil) is an oral alkylating agent specifically formulated for the treatment of certain hematologic malignancies. As a cornerstone of chemotherapy in onco-hematology, it provides a targeted approach to managing chronic lymphocytic leukemia (CLL) and specific types of non-Hodgkin lymphoma. Its mechanism of action involves cross-linking DNA strands, thereby inhibiting cancer cell replication and promoting apoptosis. Administered orally, it offers a convenient treatment option that can be managed in both clinical and outpatient settings, balancing efficacy with a well-characterized safety profile when monitored appropriately by healthcare professionals.

Features

• Active Ingredient: Chlorambucil
• Formulation: Film-coated tablets available in 2 mg strength
• Pharmacologic Class: Nitrogen mustard alkylating agent
• Administration: Oral route with flexible dosing regimens
• Bioavailability: Nearly complete gastrointestinal absorption
• Metabolism: Hepatic, primarily to phenylacetic acid mustard
• Half-life: Approximately 1.5 hours for chlorambucil, 2.5 hours for active metabolite
• Excretion: Primarily renal (60% within 24 hours)

Benefits

• Provides targeted cytotoxic activity against rapidly dividing malignant lymphocytes
• Enables oral administration facilitating outpatient treatment and improved quality of life
• Demonstrates predictable pharmacokinetics allowing for dose titration based on response
• Offers established efficacy in both treatment-naïve and previously treated patients
• Maintains manageable toxicity profile when properly monitored
• Serves as backbone therapy for combination regimens in certain hematologic malignancies

Common use

Leukeran is primarily indicated for the palliative treatment of chronic lymphocytic leukemia (CLL), Hodgkin lymphoma, and non-Hodgkin lymphoma. It is particularly effective in cases where the disease characteristics align with its mechanism of action, typically involving slowly progressive lymphoproliferative disorders. The medication may be used as monotherapy or in combination with other chemotherapeutic agents, depending on disease stage, patient characteristics, and treatment goals. Clinical decisions regarding its use should be based on comprehensive hematologic assessment, including bone marrow function evaluation and precise diagnostic classification.

Dosage and direction

Dosage must be individualized based on hematologic profile, renal function, and treatment response. The typical initial dose for CLL is 0.1-0.2 mg/kg body weight daily (approximately 4-8 mg daily for a 70 kg adult), administered as a single daily dose. Alternative intermittent dosing schedules (0.4 mg/kg administered every two weeks, increased by 0.1 mg/kg until response observed) may be employed. Tablets should be swallowed whole with water, preferably at the same time each day, with or without food. Complete blood counts should be performed weekly during therapy and dosage adjusted accordingly based on nadir counts. Treatment duration varies from continuous therapy to intermittent courses based on response and tolerance.

Precautions

Regular monitoring of complete blood counts is essential throughout therapy and for several weeks after discontinuation. Hepatic and renal function should be assessed prior to and during treatment. Patients should be advised to maintain adequate hydration. Secondary malignancies have been reported with long-term use. Vaccination with live vaccines should be avoided during treatment. Women of childbearing potential and men with partners of childbearing potential should use effective contraception. Healthcare providers should consider potential effects on fertility before initiating treatment. Patients should be monitored for signs of infection, bleeding, or anemia throughout therapy.

Contraindications

Leukeran is contraindicated in patients with demonstrated hypersensitivity to chlorambucil or any component of the formulation. It should not be administered to patients who have demonstrated prior resistance to the drug. Use is contraindicated during pregnancy unless the potential benefit justifies the potential risk to the fetus. Breastfeeding should be discontinued during treatment. The medication is contraindicated in patients with severe bone marrow suppression or those who have recently received radiation therapy or other chemotherapy causing significant myelosuppression.

Possible side effect

Hematologic: Myelosuppression (anemia, leukopenia, thrombocytopenia), which may be severe and progressive with continued administration
Gastrointestinal: Nausea, vomiting, diarrhea, oral ulceration, hepatotoxicity
Dermatologic: Skin rash, urticaria, angioedema
Neurologic: Tremors, muscle twitching, confusion, seizures (particularly at high doses)
Pulmonary: Pulmonary fibrosis, interstitial pneumonitis
Reproductive: Amenorrhea, oligospermia, azoospermia, infertility
Other: Fever, fatigue, secondary malignancies, anaphylactic reactions

Drug interaction

Live vaccines: Increased risk of vaccine-preced infection
Anticoagulants: Potential enhancement of anticoagulant effect
Myelosuppressive agents: Additive bone marrow suppression
Phenytoin: Possible decreased phenytoin levels
Suxamethonium: Prolonged apnea may occur
Immunosuppressants: Enhanced immunosuppressive effects
Nephrotoxic agents: Potential increased renal toxicity

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is nearly time for the next scheduled dose. In that case, the missed dose should be skipped and the regular dosing schedule resumed. Patients should never take a double dose to make up for a missed one. Healthcare providers should be informed about any missed doses, as this may affect treatment monitoring schedules. Consistent dosing is important for maintaining therapeutic levels while minimizing toxicity.

Overdose

Overdose may manifest as irreversible bone marrow suppression, pancytopenia, gastrointestinal toxicity, and central nervous system stimulation including seizures. There is no specific antidote for Leukeran overdose. Management involves immediate discontinuation of the drug and supportive care including transfusion of blood products, antimicrobial therapy for infections, and symptomatic treatment. Hemodialysis is not effective due to high protein binding. Hospitalization with intensive supportive care in a specialized hematology/oncology unit is recommended for significant overdoses.

Storage

Store at controlled room temperature (20-25°C or 68-77°F) in the original container. Protect from light and moisture. Keep tightly closed and out of reach of children. Do not store in bathroom or damp places. Tablets should not be removed from their blister packaging until immediately before administration. Proper disposal of unused medication should follow local regulations for cytotoxic agents, typically through take-back programs or hazardous waste disposal facilities.

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, warnings, and precautions. Patients should not alter or discontinue medication without medical supervision. While every effort has been made to ensure accuracy, medical knowledge is constantly evolving and the most current prescribing information should always be consulted.

Reviews

“Leukeran has been a mainstay in our treatment arsenal for indolent lymphoproliferative disorders for decades. Its predictable pharmacokinetics and oral administration make it particularly valuable for long-term management of appropriate patients.” - Hematologist, 15 years experience

“The balance between efficacy and toxicity requires careful monitoring, but when managed appropriately, Leukeran provides meaningful disease control with acceptable quality of life for many CLL patients.” - Oncology Pharmacist

“While newer targeted agents have expanded our options, Leukeran remains relevant particularly in resource-limited settings and for specific patient subgroups where its cost-effectiveness profile is advantageous.” - Clinical Researcher