title: Tolerability of metronomic administration of lomustine in dogs with cancer.
abstract: BACKGROUND
  Metronomic chemotherapy with alkylating agents has been shown to suppress tumor angiogenesis and prevent tumor recurrence in some settings. The use of adjuvant lomustine (1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea) administered in a metronomic fashion has not been evaluated in dogs.
  
  
  OBJECTIVE
  Oral metronomic administration of lomustine will be well tolerated in dogs with spontaneously occurring malignant neoplasms.
  
  
  METHODS
  Eighty-one dogs with naturally occurring primary or metastatic tumors received metronomic administration of lomustine.
  
  
  METHODS
  Dogs were enrolled prospectively after cytological or histological diagnosis of a tumor that was unresectable, incompletely resected, refractory to chemotherapy, or metastatic. Dogs received once daily lomustine (2.84 mg/m² PO). End points of the trial were clinical, hematologic, or biochemical evidence of toxicosis, tumor progression, or death.
  
  
  RESULTS
  Starting dosage (median) was 2.84 mg/m² PO daily and treatment duration was 98 days (median, range, 1-770 days). The drug was discontinued in 22 dogs because of toxicoses. Toxicoses occurred in 13 dogs with gastrointestinal toxicosis, 4 dogs with thrombocytopenia, 3 dogs with increased alanine transaminase, 1 dog with neutropenia, and 1 dog with progressive azotemia. Eight dogs developed some degree of azotemia during treatment. Hepatotoxicosis was observed at a median of 265 days in 11 dogs. Thrombocytopenia was identified at a median of 432 days of administration.
  
  
  CONCLUSIONS
  In dogs with metastatic or terminal neoplasms without renal compromise, metronomic administration of lomustine was well tolerated. This can provide a treatment strategy for dogs that do not have other standard-care treatment options, and warrants evaluation in primary therapy.
authors.affiliation: Department of Veterinary Clinical Sciences, Washington State University, Pullman, WA, USA.
authors.forename: C D
authors.initials: CD
authors.lastname: Tripp
authors.forename: J
authors.initials: J
authors.lastname: Fidel
authors.forename: C L
authors.initials: CL
authors.lastname: Anderson
authors.forename: M
authors.initials: M
authors.lastname: Patrick
authors.forename: C
authors.initials: C
authors.lastname: Pratt
authors.forename: R
authors.initials: R
authors.lastname: Sellon
authors.forename: J N
authors.initials: JN
authors.lastname: Bryan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D005260:Female; D008130:Lomustine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D009362:Neoplasm Metastasis / Q000188:drug therapy; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control / Q000662:veterinary; D009369:Neoplasms / Q000188:drug therapy / Q000662:veterinary*; D010166:Palliative Care; D011446:Prospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced / Q000662:veterinary; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D008130:Lomustine