Evaluation of Ifosfamide for Treatment of Various Canine Neoplasms

Ifosfamide (3‐[2‐chloroethyl]‐2[(2 chloroethyl)amino]tetrahydro‐2H‐1,3,2‐oxazaphosphorine 2‐oxide) is an alkylating agent with a broad spectrum of antitumor activity. The efficacy and toxicity of ifosfamide were evaluated in 72 dogs with spontaneously occurring tumors. Forty dogs (56%) had lymphoma, 31 (43%) had sarcomas, and 1 had a metastatic carcinoma. Five dogs received ifosfamide at dosages <350 mg/m 2 IV. Neither toxicity nor response were observed, and the remaining dogs received ifosfamide at 350 mg/m 2 (n = 18) and 375 mg/m 2 body surface area IV (n = 49). Saline diuresis and the thiol compound mesna were used to prevent urothelial toxicity. Fifty‐two dogs had measurable tumors and could be evaluated for response. Complete responses were seen in 1 dog with metastatic leiomyosarcoma of the urinary bladder and in 1 dog with metastatic cutaneous hemangiosarcoma. One dog with lymphoma had a partial response for 112 days. Six dogs with splenic hemangiosarcoma received ifosfamide post‐splenectomy and their median survival time was 147 days. The acute dose‐limiting toxicity was neutropenia 7 days after administration of ifosfamide. The median and mean neutrophil counts 7 days after ifosfamide at 350 mg/m 2 were 2,035 cells/μL and 4,773 cells/μL, respectively (n = 12). The median and mean neutrophil counts 7 days after ifosfamide at 375 mg/m 2 were 2,500 cells/μL and 3,594 cells/μL, respectively (n = 37). No dog developed clinical or microscopic evidence of hemorrhagic cystitis. Ifosfamide appears safe to use in tumor‐bearing dogs, and the evaluation of combination chemotherapy protocols that include ifosfamide should be considered.