title: Phase I/II clinical trial of encapsulated, cytochrome P450 expressing cells as local activators of cyclophosphamide to treat spontaneous canine tumours.
abstract: Based upon promising preclinical studies, a clinical trial was performed in which encapsulated cells overexpressing cytochrome P450 enzyme isoform 2B1 were implanted around malignant mammary tumours arising spontaneously in dogs. The dogs were then given cyclophosphamide, one of the standard chemotherapeutic agents used for the treatment of mammary tumours. The dogs were assessed for a number of clinical parameters as well as for reduction in tumour size. The treatment was well tolerated with no evidence of adverse reactions or side effects being associated with the administration of the encapsulated cells. Reductions in tumour size of more than 50% were observed for 6 out of the 11 tumours analysed while 5 tumours showing minor responses, i.e. stable disease. In contrast, the tumours that received cyclophosphamide alone showed only stable disease. Taken together, this data suggests that encapsulated cytochrome P450 expressing cells combined with chemotherapy may be useful in the local treatment of a number of dog mammary tumours and support the performance of further clinical studies to evaluate this new treatment.
authors.affiliation: Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences, Lublin, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Michałowska
authors.affiliation: Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences, Lublin, Poland.
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Winiarczyk
authors.affiliation: Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences, Lublin, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Adaszek
authors.affiliation: Department of Pathological Anatomy, Faculty of Veterinary Medicine, University of Life Sciences Lublin, Lublin, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Łopuszyński
authors.affiliation: Department of Epizootiology and Clinic of Infectious Diseases, Faculty of Veterinary Medicine, University of Life Sciences, Lublin, Poland.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Grądzki
authors.affiliation: Austrianova, Centros, Singapore.
authors.forename: Brian
authors.initials: B
authors.lastname: Salmons
authors.affiliation: Department of Pathobiology, Institute of Virology, University of Veterinary Medicine, Vienna, Austria.
authors.forename: Walter H
authors.initials: WH
authors.lastname: Günzburg
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002214:Capsules; D064987:Cell- and Tissue-Based Therapy / Q000009:adverse effects / Q000379:methods*; D003520:Cyclophosphamide / Q000627:therapeutic use*; D019362:Cytochrome P-450 CYP2B1 / Q000235:genetics*; D004283:Dog Diseases / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D004285:Dogs; D005260:Female; D015870:Gene Expression; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D012449:Safety; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D002214:Capsules; D003520:Cyclophosphamide; D019362:Cytochrome P-450 CYP2B1