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Olsson, Angelika, 2010. Farmakogenomikens betydelse för individvariationen avseende biverkningar och resultat vid Paclitaxel behandling av hund. Second cycle, A1N, A1F or AXX ( AXX). Uppsala: SLU, Dept. of Clinical Sciences (until 231231)



The purpose of this study is to evaluate the treatment results and adverse drug effects for 14 dogs receiving a new paclitaxel preparat named Paccal vet. The evaluated dogs are chosen to enter a pharmacogenomical study. Therefore, this paper intends to give an introduction to pharmacogenomics. Finally this study also aims at finding the homologue genesequenses in dogs to seven genes that are important for metabolism of paclitaxel in humans.

Materials and metods
The dogs went through 2-4 cycles of paclitaxel treatment, they received a new water-soluble formula named Paccal vet, at dosages of 100-150mg/m2. Treatment results and adverse effects are listed for each dog in table 1. Gastrointestinal side effects are listed once per dog, bone marrow suppression is listed for each cycle.

The dogs’ DNA is prepared from frozen EDTA-bloodsamples. As a result of the creation of different breeds, dogs have very long haplotypes, in which no recombination occurs. Therefore there can’t be an easily accessed map of haplotypes. Instead, one have to assume that by using at least five SNPs per gene of interest all different haplotypes can be covered. After deciding which SNPs to use, the primers for amplifying can be designed by help of different computer programmes.

All dogs tolerated the substance well; no sensitivity reactions were observed. The most frequent side-effects were bone marrow depression and gastrointestinal upset.

At an initial search for the homologue sequences of the chosen genes, only a few were found. The same sequence also showed up for different genes, thus revealing that it may be quite complicated to find the desired homologues, much due to the fact that some of the genes are very similar to each other.

The fact that dogs seem to tolerate Paccal vet, and the side-effects being manageable, gives a promising future to further studies following up on this small pilot study. It is the first cytostatica made particularly for dogs and also the first paclitaxel preparat tolerated by dogs.

However it is a study of very few dogs whom varied greatly in gender, breed, age and size. They also suffered from different diseases in different stages which makes the results unreliable.

The further farmacogenomic study of these dogs can although it is small be of great importance. It can show whether the canine genome shows polymorphism in those genes or not. If so, analysis of the results may strengthen the hypothesis that this polymorphism is strongly responsible for the individual variations in dogs as well.

The concept of individualizing cancer therapy is one of great appeal, and world wide scientists are digging in to farmacogenomics. Only the future can answer how it will be applied in veterinary medicine. First we need to establish that polymorphism of interesting genes span over breed boundaries, thus it is unrealistic to keep one gene map per breed. However, if this is the case, farmacogenomic testing can prove to be of great value.

For dogs with cancer, euthanasia often is a considered alternative, which puts the pet owner and sometimes also the veterinarian in a tough position. It would be of immeasurable value if a simple test could be taken, that answers the question whether this patient has a low or high probability to benefit from treatment.

Main title:Farmakogenomikens betydelse för individvariationen avseende biverkningar och resultat vid Paclitaxel behandling av hund
Authors:Olsson, Angelika
Supervisor:Von Euler, Henrik and Rivera, Patricio
Examiner:Jones, Bernt
Series:Examensarbete / Sveriges lantbruksuniversitet, Fakulteten för veterinärmedicin och husdjursvetenskap, Veterinärprogrammet
Volume/Sequential designation:2009:3
Year of Publication:2010
Level and depth descriptor:Second cycle, A1N, A1F or AXX
Student's programme affiliation:3050A Veterinary Medicine Programme (admitted before July 1, 2007) 330 HEC
Supervising department:(VH) > Dept. of Clinical Sciences (until 231231)
Keywords:Farmakogenomik, Paccal vet, Paclitaxel, cytochrom p450, cytistatikabehandling av hund
Permanent URL:
Subject. Use of subject categories until 2023-04-30.:Animal diseases
Deposited On:29 Jan 2010 12:00
Metadata Last Modified:05 Oct 2012 18:24

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