title: Evaluation of ifosfamide for treatment of various canine neoplasms.
abstract: lfosfamide (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/m2 IV. Neither toxicity nor response were observed, and the remaining dogs received ifosfamide at 350 mg/m2 (n = 18) and 375 mg/m2 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 postsplenectomy 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/m2 were 2,035 cells/microL and 4,773 cells/microL, respectively (n = 12). The median and mean neutrophil counts 7 days after ifosfamide at 375 mg/m2 were 2,500 cells/microL and 3,594 cells/microL, 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.
authors.affiliation: Harrington Oncology Program, School of Veterinary Medicine, Tufts University, North Grafton, MA 01536, USA. krassnick@infonet.tufts.edu
authors.forename: K M
authors.initials: KM
authors.lastname: Rassnick
authors.forename: A E
authors.initials: AE
authors.lastname: Frimberger
authors.forename: C A
authors.initials: CA
authors.lastname: Wood
authors.forename: L E
authors.initials: LE
authors.lastname: Williams
authors.forename: S M
authors.initials: SM
authors.lastname: Cotter
authors.forename: A S
authors.initials: AS
authors.lastname: Moore
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy* / Q000401:mortality; D004285:Dogs; D005260:Female; D007069:Ifosfamide / Q000627:therapeutic use*; D008223:Lymphoma / Q000188:drug therapy / Q000401:mortality / Q000662:veterinary*; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D011996:Records / Q000662:veterinary; D012189:Retrospective Studies; D012509:Sarcoma / Q000188:drug therapy / Q000401:mortality / Q000662:veterinary*; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D007069:Ifosfamide