Thymidylate synthase and dihydropyrimidine dehydrogenase expression levels are associated with response to S-1 plus carboplatin in advanced non-small cell lung cancer

Lung Cancer. 2011 Jul;73(1):103-9. doi: 10.1016/j.lungcan.2010.10.022. Epub 2010 Dec 7.


S-1 is an oral fluoropyrimidine derivative that is active against non-small cell lung cancer (NSCLC). Development of S-1 combination chemotherapy for advanced NSCLC is under way. Given the importance of designing therapeutic strategies based on specific tumor biology, we have evaluated the relation between immunohistochemical expression levels of thymidylate synthase (TS), orotate phosphoribosyltransferase (OPRT), or dihydropyrimidine dehydrogenase (DPD) and the response to treatment with S-1 plus carboplatin in patients with advanced NSCLC. Chemotherapy-naïve patients with advanced (stage IIIB or IV) NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, adequate organ function, and archival tumor tissue were assigned to receive S-1-carboplatin (n=22). The predictive or prognostic relevance of the molecular markers was also examined by their evaluation in patients treated with paclitaxel plus carboplatin (n=25). Expression levels of TS, OPRT, or DPD in tumor specimens did not differ significantly between patients treated with S-1-carboplatin and those treated with paclitaxel-carboplatin. A low expression level of TS or of DPD was associated with a better response and longer survival in patients treated with S-1-carboplatin but not in those treated with paclitaxel-carboplatin. Tumor expression levels of TS and DPD are predictive of response to S-1-carboplatin chemotherapy in patients with advanced NSCLC.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Carboplatin / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / enzymology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Dihydrouracil Dehydrogenase (NADP) / metabolism*
  • Disease-Free Survival
  • Drug Combinations
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Orotate Phosphoribosyltransferase / metabolism
  • Oxonic Acid / administration & dosage
  • Paclitaxel / administration & dosage
  • ROC Curve
  • Tegafur / administration & dosage
  • Thymidylate Synthase / metabolism*
  • Treatment Outcome


  • Biomarkers, Tumor
  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Carboplatin
  • Dihydrouracil Dehydrogenase (NADP)
  • Thymidylate Synthase
  • Orotate Phosphoribosyltransferase
  • Paclitaxel