title: Evaluation of low-dose metronomic (LDM) cyclophosphamide toxicity in cats with malignant neoplasia.
abstract: Oral administration of low-dose cyclophosphamide in pets with spontaneously occurring malignant neoplasms has become a common practice in veterinary medicine. The purpose of this retrospective study was to investigate toxicity events in cats with spontaneous malignancies receiving cyclophosphamide as a metronomic therapy for at least 1 month. The number and severity of clinical, haematological and biochemical adverse events were recorded according to the Veterinary Cooperative Oncology Group's Common Terminology Criteria for Adverse Events v1.1 classification scheme. Twenty-four cats were enrolled in the study with a total number of 27 neoplasms: 13 sarcomas, 12 carcinomas, one melanoma and one neuroendocrine tumour. Seventeen cats presented with macroscopic disease, while seven had microscopic disease. Seven cats (29%) had metastasis either to the regional lymph nodes and/or distant sites at the time of study enrolment. Additional medications, administered concurrently, included non-steroidal anti-inflammatory drugs (17), toceranib (4) and thalidomide (7). Four cats showed grade I gastrointestinal toxicity during the first month of treatment, which was controlled with antiemetics. Overall, 2/24 cats (8%) showed grade I haematological toxicities and 1/24 (4%) showed grade I renal toxicity in the first 4 weeks. Median follow-up for all cats was 30 days (range 30-360 days). For the 15 cats with follow-up longer than 1 month the only additional toxicities observed were two grade III and one grade II azotaemia that occurred after 2 months of therapy. Low-dose cyclophosphamide seems to be a well-tolerated option for cats bearing primary or metastatic tumours. Evaluation of toxicity after long-term administration is still needed.
authors.affiliation: Oncology Service, Royal Veterinary College, University of London, London, UK cleo@rvc.ac.uk.
authors.forename: Chiara
authors.initials: C
authors.lastname: Leo
authors.affiliation: Oncology Service, Royal Veterinary College, University of London, London, UK.
authors.forename: Anneliese
authors.initials: A
authors.lastname: Stell
authors.affiliation: Veterinary Institute of Comparative Oncology, Valencia, Spain Veterinary Hospital, University of Veterinary and Experimental Sciences, Catholic University of Valencia 'San Vicente Martir', Valencia, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Borrego
authors.affiliation: Department of Animal Medicine and Surgery, Facultad de Veterinaria Avda, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Martinez de Merlo
authors.affiliation: Animal Oncology and Imaging Center, Hünenberg, Switzerland.
authors.forename: Katja
authors.initials: K
authors.lastname: Ruess-Melzer
authors.affiliation: Oncology Service, Royal Veterinary College, University of London, London, UK.
authors.forename: Ana
authors.initials: A
authors.lastname: Lara-Garcia
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects; D002371:Cat Diseases / Q000139:chemically induced*; D002415:Cats; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects*; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D009367:Neoplasm Staging; D009369:Neoplasms / Q000188:drug therapy / Q000662:veterinary*; D012189:Retrospective Studies
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide