Tolerability and pharmacokinetic profile of a novel benzene-poly-carboxylic acids complex with cis-diammineplatinum (II) dichloride in dogs with malignant mammary tumours

Vet Comp Oncol. 2017 Mar;15(1):118-132. doi: 10.1111/vco.12144. Epub 2015 Mar 12.

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.

Keywords: BP-C1; Immovet-C8; Response Surface Pathway (RSP) design; canine cancer; dose response; mammary cancer.

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics*
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / pharmacokinetics*
  • Benzene / pharmacology
  • Carboxylic Acids / pharmacology
  • Carcinoma / pathology
  • Carcinoma / veterinary*
  • Cisplatin / administration & dosage
  • Cisplatin / adverse effects
  • Cisplatin / pharmacokinetics*
  • Dog Diseases / drug therapy*
  • Dog Diseases / pathology
  • Dogs
  • Dose-Response Relationship, Drug
  • Female
  • Half-Life
  • Mammary Neoplasms, Animal / drug therapy*
  • Maximum Tolerated Dose
  • Norway

Substances

  • Antineoplastic Agents
  • Carboxylic Acids
  • Benzene
  • Cisplatin