title: Tolerability and pharmacokinetic profile of a novel benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride in dogs with malignant mammary tumours.
abstract: The pharmacokinetic profile, tolerability and efficacy of benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride (BP-C1) were studied in dogs with mammary cancer. A three-level response surface pathway designed trial was performed on seven dogs. At each level BP-C1 was administered subcutaneously daily for 7 days followed by a 7-day rest period in a dose escalating manner. Adverse events according to VCOG-CTCAE, performance status and tumour progression were recorded. The pharmacokinetic profile followed a two-compartment model with rapid absorption, short distribution, and a slow elimination phase. The overall elimination half-life was 125 h. The maximum tolerated dose of BP-C1 was estimated to be above 0.46 mg kg-1. A significant reduction in VCOG-CTCAE toxicity which correlated negatively with increasing dose was found. The dogs' general performance status remained unchanged. No decrease in total tumour burden was found, although temporary tumour reduction was seen in some target tumours.
authors.affiliation: Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway.
authors.forename: V M
authors.initials: VM
authors.lastname: Kristiansen
authors.affiliation: Centre for Epidemiology and Biostatistics, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Dewi
authors.affiliation: Department of Food Safety and Infection Biology, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway.
authors.forename: T E
authors.initials: TE
authors.lastname: Horsberg
authors.affiliation: Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway.
authors.forename: T J
authors.initials: TJ
authors.lastname: Jonasdottir
authors.affiliation: Department of Companion Animal Clinical Sciences, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway.
authors.forename: L
authors.initials: L
authors.lastname: Moe
authors.affiliation: Department of Chemical and Biological Work Environment, National Institute of Occupational Health, Oslo, Norway.
authors.forename: B
authors.initials: B
authors.lastname: Berlinger
authors.affiliation: Department of Surgery and Cancer, Hammersmith Hospital Campus, Imperial College London, London, United Kingdom.
authors.forename: S
authors.initials: S
authors.lastname: Lindkaer-Jensen
authors.affiliation: Centre for Epidemiology and Biostatistics, Faculty of Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Larsen
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001554:Benzene / Q000494:pharmacology; D002264:Carboxylic Acids / Q000494:pharmacology; D002277:Carcinoma / Q000473:pathology / Q000662:veterinary*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D004283:Dog Diseases / Q000188:drug therapy* / Q000473:pathology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006207:Half-Life; D015674:Mammary Neoplasms, Animal / Q000188:drug therapy*; D020714:Maximum Tolerated Dose; D009664:Norway
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D001554:Benzene; D002945:Cisplatin
keywords: BP-C1; Immovet-C8; Response Surface Pathway (RSP) design; canine cancer; dose response; mammary cancer