Thymidylate synthase genotype-directed chemotherapy for patients with gastric and gastroesophageal junction cancers

Laura W. Goff, Nilay Thakkar, Liping Du, Emily Chan, Benjamin R. Tan, Dana B. Cardin, Howard L. McLeod, Jordan D. Berlin, Barbara Zehnbauer, Chloe Fournier, Joel Picus, Andrea Wang-Gillam, Wooin Lee, A. Craig Lockhart

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3 Scopus citations


Background: Retrospective studies indicate associations between TSER (thymidylate synthase enhancer region) genotypes and clinical outcomes in patients receiving 5-FU based chemotherapy, but well-controlled prospective validation has been lacking.

Methods: In this phase II study (NCT00515216 registered through, NCT00515216), patients with ''good risk'' TSER genotypes (at least one TSER2 allele) were treated with FOLFOX chemotherapy to determine whether prospective patient selection can improve overall response rates (ORR) in patients with gastric and gastroesophageal junction (GEJ) cancers, compared with historical outcomes in unselected patients (estimated 43%).

Results: The ORR in genotype-selected patients was 39.1% (9 partial responses out of 23 evaluable patients, 95% CI, 22.2 to 59.2), not achieving the primary objective of improving ORR. An encouraging disease control rate (DCR, consisting of partial responses and stable diseases) of 95.7% was noted and patients with homozygous TSER 2 genotype showed better tumor response.

Conclusions: In this first prospective, multi-institutional study in patients with gastric or GEJ cancers, selecting patients with at least one TSER 2 allele did not improve the ORR but led to an encouraging DCR. Further studies are needed to investigate the utility of selecting patients homozygous for the TSER2 allele and additional genomic markers in improving clinical outcomes for patients with gastric and GEJ cancers. Copyright:

Original languageEnglish
Article numberA1407
JournalPloS one
Issue number9
StatePublished - Sep 18 2014


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