29
views
0
recommends
+1 Recommend
0 collections
    8
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Relations between polymorphisms in drug-metabolising enzymes and toxicity of chemotherapy with cyclophosphamide, thiotepa and carboplatin.

      Pharmacogenetics and Genomics

      Adolescent, Adult, Carboplatin, administration & dosage, adverse effects, pharmacology, therapeutic use, Cyclophosphamide, Female, Gene Frequency, Genotype, Humans, Inactivation, Metabolic, genetics, Male, Middle Aged, Neoplasms, drug therapy, Polymorphism, Single Nucleotide, Thiotepa

      Read this article at

      ScienceOpenPublisherPubMed
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          High-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin (CTC) has been developed as a possible curative treatment modality in several solid tumours. However, a large interindividual variability in toxicity is encountered in high-dose chemotherapy. A priori identification of patients at risk for toxicity could be an attractive prospect. Genotyping of genes encoding drug-metabolising enzymes might provide such a tool. We assessed 16 selected polymorphisms in nine genes (CYP2B6, CYP2C9, CYP2C19, CYP3A4, CYP3A5, GSTA1, GSTP1, ALDH1A1 and ALDH3A1) of putative relevance in CTC metabolism using polymerase chain reaction and DNA sequencing in 113 patients who were treated with high-dose chemotherapy regimens based on CTC. Patients heterozygous for the ALDH3A1*2 allele (allelic frequency 21.2%) had an increased risk of haemorrhagic cystitis when compared with patients with wild-type alleles [5/38 vs. 1/70; odds ratio (OR): 11.95, 95% confidence interval (CI): 1.18-120.56; P=0.04]. Furthermore, patients heterozygous for the ALDH1A1*2 allele (allelic frequency 5.8%) had an increased risk of liver toxicity when compared with patients with wild-type alleles (6/13 vs. 19/99; OR: 5.13, 95% CI: 1.30-20.30; P=0.02). No other relations reached significance. Patients heterozygous for the ALDH3A1*2 and ALDH1A1*2 allele have an increased risk of haemorrhagic cystitis and liver toxicity, respectively, compared with patients with wild-type alleles when treated with a high-dose chemotherapy combination of CTC. Pharmacogenetic approaches can identify patients who are at risk of experiencing toxic side effects in high-dose chemotherapy.

          Related collections

          Author and article information

          Journal
          18854779
          10.1097/FPC.0b013e328313aaa4

          Comments

          Comment on this article