Genotype-guided neoadjuvant therapy for rectal cancer

3024 Background: Neoadjuvant therapy with 5-fluorouracil (5FU) and radiation has become standard therapy for bulky rectal cancer and achieves a downstaging (DS) rate of 45%. The presence of two 28 bp repeats (*2) in thymidylate synthase was recently associated with superior DS (60%) compared with homozygous triple repeat (*3/*3; 22% DS) (J Clin Oncol 2001;19:1779–86). Multiple studies have linked TYMS *3/*3 with risk of 5FU failure. Pharmacogenomics has provided the promise of better therapy, based on retrospective evaluation of patient treatment. Therefore a study was conducted to provide initial experience with the conduct of genotype-guided therapy and to generate data for the design of future randomized pharmacogenomics trials. Methods: A two-stage design was used to construct 2 distinct phase II studies, directed by TYMS genotype. After informed consent, patients with stage T3/T4 rectal cancer were genotyped for the TYMS repeat sequence. ’Good risk’ patients (TYMS *2/*2 or *2/*3) received 5 weeks of ...