title: Retrospective comparison of three doses of metronomic chlorambucil for tolerability and efficacy in dogs with spontaneous cancer.
abstract: The study hypothesis is that higher doses of metronomic (low-dose) chlorambucil will improve outcome without significantly worsening adverse events (AE). Retrospectively, 88 dogs were screened to assess for tolerability and response to chlorambucil utilizing retrospective and prospective data sets, comparing metronomic oral daily doses 4, 6 and 8 mg m2. There were 78 and 70 dogs in the tolerability and efficacy portions, respectively. The severity of gastrointestinal (GI) AE was significantly worse, and time to development of GI events was significantly shorter at 6 mg m2than at 4 mg m2(both P < 0.001). Chlorambucil was discontinued earlier in the dogs treated at the 6 mg m2doses than in the dogs treated at 4 mg m2(P = 0.015). Thrombocytopenia occurred significantly earlier at 8 mg m2than at 4 mg m2(P = 0.017). Higher doses of metronomic (low-dose) chlorambucil did not provide improved responses and were associated with more AE.
authors.affiliation: Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN, USA.
authors.forename: M R
authors.identifier: http://orcid.org/0000-0001-7665-1625
authors.initials: MR
authors.lastname: Custead
authors.affiliation: Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, USA.
authors.forename: H Y
authors.initials: HY
authors.lastname: Weng
authors.affiliation: Department of Veterinary Clinical Sciences, Purdue University, West Lafayette, IN, USA.
authors.forename: M O
authors.initials: MO
authors.lastname: Childress
mesh_terms: D059250:Administration, Metronomic / Q000662:veterinary; D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D002699:Chlorambucil / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000662:veterinary*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002699:Chlorambucil
keywords: Leukeran; cancer; chemotherapy; low-dose; small-animal