Ifosfamide

From Dog

Ifosfamide is a oxazaphosphorine nitrogen mustard alkylating prodrug used in chemotherapy for solid tumors in dogs.

This drug has been used for treatment of osteosarcoma[1], cutaneous hemangiosarcoma, lymphoma[2] and leiomyosarcoma. Variable responses have been reported, with only 12% of osteosarcoma patients responding[3].

It is often used in conjunction with mesna (to avoid hemorrhagic cystitis), which is first given as a bolus, followed by diuresis then ifosfamide therapy.

Transient liver, renal and bone marrow toxicity and gastrointestinal dysfunction were seen at low doses[4] and leukopenia at high doses (>450 mg/m2)[5].

Recommended dose rate in dogs is 375 - 425 mg/m2.

References

  1. Germann N et al (2005) Comparative preclinical toxicology and pharmacology of isophosphoramide mustard, the active metabolite of ifosfamide. Cancer Chemother Pharmacol 55(2):143-151
  2. Rassnick KM et al (2000) Evaluation of ifosfamide for treatment of various canine neoplasms. J Vet Intern Med 14(3):271-276
  3. Batschinski K et al (2012) Evaluation of ifosfamide salvage therapy for metastatic canine osteosarcoma. Vet Comp Oncol Sep 18
  4. Chen CS et al (2004) Activation of the anticancer prodrugs cyclophosphamide and ifosfamide: identification of cytochrome P450 2B enzymes and site-specific mutants with improved enzyme kinetics. Mol Pharmacol 65(5):1278-1285
  5. Ikeda K et al (1996) Development of a canine chemotherapeutic model with ifosfamide. Lab Anim Sci 46(5):503-506