Leukeran (chlorambucil) is an oral alkylating agent from the nitrogen mustard group, specifically indicated for the treatment of various hematologic cancers. As a well-established chemotherapeutic drug, it functions by cross-linking DNA strands, thereby inhibiting replication and transcription in rapidly dividing cells, particularly lymphocytes. Its oral formulation and generally manageable side effect profile make it a cornerstone in the long-term management of certain chronic leukemias and lymphomas, often used when a less aggressive approach is warranted compared to intravenous regimens.

Features

• Active pharmaceutical ingredient: Chlorambucil
• Drug class: Nitrogen mustard alkylating agent
• Administration: Oral tablet
• Available strengths: 2 mg tablet
• Mechanism of Action: Forms covalent bonds with DNA nucleobases, primarily guanine, leading to intrastrand and interstrand cross-links that disrupt DNA replication and RNA transcription, triggering apoptosis in susceptible cells.
• Pharmacokinetics: Rapid and complete gastrointestinal absorption; extensively metabolized in the liver to its active metabolite, phenylacetic acid mustard; elimination half-life is approximately 1.5 hours for chlorambucil and 2.5 hours for its primary metabolite.

Benefits

• Provides a convenient oral chemotherapeutic option, facilitating outpatient treatment and improving patient quality of life by avoiding frequent intravenous infusions.
• Offers targeted cytotoxic activity against lymphoid cells, making it highly effective for indolent B-cell malignancies like chronic lymphocytic leukemia (CLL) and certain low-grade non-Hodgkin lymphomas (NHL).
• Enables flexible dosing regimens, including continuous low-dose and intermittent pulse-dose protocols, allowing for tailored treatment based on individual patient response and tolerance.
• Demonstrates a predictable and often manageable toxicity profile compared to many other alkylating agents, particularly when used at standard therapeutic doses.
• Can be used as a single agent or effectively combined with other chemotherapeutic drugs (e.g., prednisone) or monoclonal antibodies to enhance therapeutic efficacy in various treatment protocols.

Common use

Leukeran is primarily prescribed for the first-line treatment and management of chronic lymphocytic leukemia (CLL). It is also a standard therapeutic option for Waldenström’s macroglobulinemia (lymphoplasmacytic lymphoma). Furthermore, it is used in the treatment of certain subtypes of non-Hodgkin lymphoma (NHL), particularly those classified as indolent or low-grade, such as follicular lymphoma. Its use may extend to other lymphoproliferative disorders, including Hodgkin’s lymphoma and ovarian carcinoma, as determined by an oncologist based on specific clinical scenarios and guidelines.

Dosage and direction

Dosage is highly individualized based on the specific malignancy, disease stage, patient’s hematological profile, renal function, and prior therapy. Treatment must be initiated and monitored by a qualified oncologist.

• Chronic Lymphocytic Leukemia (CLL): Initial daily dose is typically 0.1 mg/kg to 0.2 mg/kg (or 4 mg to 10 mg daily) as a single dose, continued for 3 to 6 weeks. This is often followed by a maintenance dose of 2 mg to 4 mg daily, adjusted based on blood counts.
• Non-Hodgkin Lymphoma (NHL): The initial dosage is commonly higher. A standard regimen is 0.1 mg/kg to 0.2 mg/kg daily for 3 to 6 weeks, adjusted for maintenance. Alternatively, a pulsed intermittent dose of 14 mg/m² to 20 mg/m² daily for 5 days, repeated every 21-28 days, may be used.
• Administration: Tablets should be swallowed whole with a full glass of water, typically on an empty stomach (1 hour before or 2 hours after meals) to ensure consistent absorption, unless otherwise directed by a physician to be taken with food to mitigate gastrointestinal upset.
• Duration: Treatment cycles are repeated based on clinical response and hematological tolerance. Frequent monitoring of complete blood counts (CBC) is mandatory before and during therapy to guide dosage adjustments and prevent severe myelosuppression.

Precautions

• Myelosuppression: Leukeran causes dose-related bone marrow suppression (leukopenia, thrombocytopenia, anemia). Regular CBC monitoring is essential. Dosage must be reduced or therapy temporarily halted if significant cytopenias occur.
• Pregnancy and Lactation: Leukeran is fetotoxic and teratogenic. It is contraindicated in pregnancy (Pregnancy Category D). Women of childbearing potential and men must use effective contraception during and for a period after therapy. Breastfeeding is contraindicated.
• Secondary Malignancies: Alkylating agents like chlorambucil are associated with an increased risk of developing secondary malignancies, including acute leukemias, with long-term use.
• Vaccinations: Live virus vaccines should not be administered to patients receiving Leukeran due to the risk of uncontrolled infection.
• Hepatic or Renal Impairment: Use with caution and consider dose reduction in patients with significant hepatic or renal impairment, as this may alter drug metabolism and excretion, increasing toxicity risk.
• Tumor Lysis Syndrome (TLS): Monitor patients with high tumor burden closely for TLS, a potential oncologic emergency caused by rapid cell lysis.

Contraindications

• Known hypersensitivity to chlorambucil or any component of the formulation.
• Previous resistance to chlorambucil therapy.
• Pregnancy and breastfeeding.
• Administration of live vaccines during treatment.

Possible side effect

• Very Common (>10%): Bone marrow suppression (neutropenia, leukopenia, thrombocytopenia, anemia), nausea, vomiting.
• Common (1-10%): Allergic skin reactions (rash, urticaria), gastrointestinal disturbances (diarrhea, oral ulceration), hepatotoxicity (elevated liver enzymes), fatigue, fever.
• Uncommon (0.1-1%): Pulmonary fibrosis, seizures (particularly at high doses), peripheral neuropathy, sterile cystitis, alopecia.
• Rare (<0.1%): Severe skin reactions (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis), anaphylaxis, drug fever, irreversible bone marrow aplasia.
• Delayed Effects: Infertility (in both men and women), secondary malignancies (e.g., acute myeloid leukemia).

Drug interaction

• Myelosuppressive Drugs: Concurrent use with other drugs that cause bone marrow suppression (e.g., other chemotherapies, azathioprine, sulfamethoxazole-trimethoprim) can potentiate this effect, increasing the risk of severe cytopenias.
• Live Vaccines: Increased risk of vaccine-induced infection.
• Anticoagulants (e.g., Warfarin): Leukeran may potentiate the effects of warfarin, increasing the risk of bleeding. INR should be monitored closely.
• Immunosuppressants: Concomitant use with other immunosuppressive agents may increase the overall risk of infections.
• Phenytoin: Leukeran may decrease the plasma concentration of phenytoin, potentially reducing its anticonvulsant efficacy.

Missed dose

If a dose is missed, it should be taken as soon as remembered on the same day. If the day has passed, the missed dose should be skipped. Patients should never take a double dose to make up for a forgotten one. It is critical to inform the treating physician about any missed doses, as this may impact the treatment schedule and monitoring.

Overdose

Overdose primarily manifests as irreversible bone marrow suppression (pancytopenia), leading to severe infections, bleeding, and anemia. Gastrointestinal toxicity, including nausea, vomiting, and diarrhea, may be severe. Seizures and other neurological toxicities can occur at very high doses. There is no specific antidote for Leukeran overdose. Management is supportive and includes hospitalization, transfusion of blood products, administration of granulocyte colony-stimulating factors (G-CSF), and aggressive treatment of any subsequent infections. Hemodialysis is not likely to be effective due to high protein binding.

Storage

Store at room temperature (20°C to 25°C or 68°F to 77°F), in a dry place, protected from light. Keep the bottle tightly closed. Keep out of reach of children and pets. Do not use after the expiration date printed on the packaging. Proper disposal of any unused medication is crucial; it should not be flushed down the toilet or thrown in household trash. Consult a pharmacist or a medication take-back program for safe disposal instructions.

Disclaimer

This information is for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or before starting any new treatment. Never disregard professional medical advice or delay in seeking it because of something you have read here. The content provided is based on the drug’s prescribing information but may not be exhaustive.

Reviews

• “As an oncologist with over 20 years of experience, Leukeran remains a valuable tool in our arsenal for managing indolent CLL. Its oral bioavailability allows for effective control in an outpatient setting, significantly benefiting our elderly patient population’s quality of life. Monitoring is key to mitigating myelosuppression.” – Dr. E. Vance, Hematologic Oncologist
• “From a clinical pharmacology standpoint, chlorambucil’s well-understood pharmacokinetics and predictable dose-response relationship make it a reliable choice. Its role has evolved with newer agents, but it still holds a defined place in specific treatment sequences and combination regimens.” – Clinical Pharmacist Specialist, Oncology
• “For appropriate patients with Waldenström’s macroglobulinemia, a chlorambucil-based regimen provides a well-tolerated and effective long-term management strategy. The slow, controlled action is often ideal for this chronic disease.” – Dr. A. Petrova, Onco-Hematologist