Chlorambucil

Chlorambucil: Uses, Dosage and Side Effects

Overview

An alkylating agent that inhibits DNA synthesis and function through cross-linking with cellular DNA.

Uses of Chlorambucil

• Management of some malignancies including in some metronomic chemotherapy protocols.
• May be useful in the treatment of feline pemphigus foliaceus and severe feline eosinophilic granuloma complex.
• Management of lymphoproliferative, myeloproliferative and immune-mediated diseases including protein-losing enteropathy.

Dose of Chlorambucil in Dogs and Cats

• Dogs: (Give with food)
  • Chronic lymphocytic leukemia: 2–6 mg/m2 p.o. q24h initially until remission achieved, then at reduced dosage/frequency as required to maintain remission; or 0.2 mg/kg q24h for 7 days then 0.1 mg/kg q24h for maintenance; or 20 mg/m2 every 1–2 weeks. Often used with prednisolone 40 mg/m2 p.o. q24h for 7 days then 20 mg/m2 q48h.
  • Lymphoma: 15–20 mg/m2 p.o. q2wk with prednisolone; or 2–6 mg/m2 q24–48h. 1.4 mg/kg p.o. as a single dose as a substitute for cyclophosphamide in CHOP-type protocols.
  • Pemphigus complex (in combination with corticosteroids): 0.1–0.2 mg/kg p.o. q24h initially until marked improvement of clinical signs; then alternate-day dosing, often for several weeks.
  • Protein-losing enteropathy and other immune-mediated diseases: 2–6 mg/m2 p.o. q24h until clinical remission, then tapered to the minimum effective dose.
  • For metronomic chemotherapy: 4 mg/m2 p.o. q24h.

• Cats: (Give with food)
  • Immune-mediated disease: cats >4 kg: 2 mg (total dose) p.o. q48h for 2–4 weeks, then tapered to the lowest effective dose; cats <4 kg started at 2 mg (total dose) q72h.
  • Chronic lymphocytic leukemia: 2 mg/m2 p.o. q48h or 20 mg/m2 q14d, with or without prednisolone.
  • For low-grade/small cell lymphoma: 20 mg/m2 p.o. once every two weeks with prednisolone.
  • As a substitute for cyclophosphamide in the CHOP protocol: 1.4 mg/kg p.o. once.
  • Feline pemphigus foliaceus or severe feline eosinophilic granuloma complex (in combination with corticosteroids): 0.1–0.2 mg/kg p.o. q24h until marked improvement of clinical signs; then alternate-day dosing, often for several weeks.

Side Effects of Chlorambucil in Dogs and Cats

• Anorexia, nausea, vomiting, leucopenia, thrombocytopenia,and anemia (rarely).
• Neurotoxicity (one case reported in a cat).
• Alopecia (rarely) and slow regrowth of clipped hair coat.
• Chlorambucil was suspected to have caused seizures in one dog.

Contraindications of Chlorambucil in Dogs and Cats

• Bone marrow suppression

Some Notes:

• Drugs that stimulate the hepatic cytochrome P450 system increase cytotoxic effects.
• Prednisolone has a synergistic effect in the management of lymphoid neoplasia.