title: Cost effectiveness of pharmacogenetic testing for uridine diphosphate glucuronosyltransferase 1A1 before irinotecan administration for metastatic colorectal cancer.
abstract: BACKGROUND
  The objective of this study was to examine the cost effectiveness of using a pharmacogenetic test for uridine diphosphate glycosyltransferase 1A1*28 (UGT1A1*28) variant homozygosity before administering irinotecan to patients with metastatic colorectal cancer.
  
  
  METHODS
  A decision-analytic model from the Medicare payer perspective followed hypothetical patients who were treated with combined 5-fluorouracil, leucovorin, and irinotecan. Under usual care, patients received a full dose of irinotecan. With genetic testing, irinotecan dosage was reduced 25% in homozygotes with the UGT1A1*28 variant allele. Test performance, chemotherapy toxicity, and quality-of-life weights were derived from clinical literature and product labels, and costs were derived from 2007 Medicare fee schedules. Chemotherapy efficacy after dose reduction, adverse event risk, and other parameters were varied in 1-way and probabilistic sensitivity analyses. The authors also calculated the value of investing in further studies of chemotherapy efficacy after homozygote dose reductions.
  
  
  RESULTS
  Pretreatment genetic testing costs less ($272 savings per patient tested) and yields slightly improved quality-adjusted life expectancy (0.1 quality-adjusted day per patient tested; approximately 2 quality-adjusted hours). Results depended on treatment efficacy but not adverse event risk assumptions. The results indicated that testing would avoid 84 cases of severe neutropenia, including 4.4 deaths. At a threshold of $100,000 per quality-adjusted life year, the therapeutic efficacy of irinotecan in homozygotes after dose reduction had to be > or =98.4% of full-dose efficacy for genetic testing to remain preferred. Future studies to determine whether this efficacy level can be achieved have an economic value of $22 million.
  
  
  CONCLUSIONS
  The current results indicated that pharmacogenetic testing for UGT1A1*28 variant homozygosity may be cost effective, but only if irinotecan dose reduction in homozygotes does not reduce efficacy. Future studies to evaluate reduced-dose efficacy in homozygotes should be considered.
authors.affiliation: Department of Public Health, Weill Cornell Medical College, New York, NY, USA. heg2001@med.cornell.edu
authors.forename: Heather Taffet
authors.initials: HT
authors.lastname: Gold
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Hall
authors.forename: Victoria
authors.initials: V
authors.lastname: Blinder
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Schackman
mesh_terms: D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000191:economics* / Q000235:genetics* / Q000473:pathology; D003362:Cost-Benefit Analysis; D003663:Decision Trees; D005820:Genetic Testing; D014644:Genetic Variation; D014453:Glucuronosyltransferase / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D000077146:Irinotecan; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D011788:Quality of Life; D000099148:UGT1A1 Enzyme
chemical_list: D002166:Camptothecin; D014453:Glucuronosyltransferase; D000077146:Irinotecan; D000099148:UGT1A1 Enzyme