Correlation between S-1 treatment outcome and expression of biomarkers for refractory thymic carcinoma

BMC Cancer. 2016 Feb 25:16:156. doi: 10.1186/s12885-016-2159-7.

Abstract

Background: Thymic carcinoma is a rare cancer with minimal evidence of a survival benefit following chemotherapy. An oral fluoropyrimidine of S-1, however, is the recommended active cytotoxic chemotherapy agent for refractory thymic carcinoma based on a case series, whereas sunitinib or everolimus are recommended as molecular-targeted agents based on Phase II trials. We retrospectively investigated the efficacy of S-1 for refractory thymic carcinoma and performed a biomarker analysis.

Methods: We assessed the clinicopathological variables of 14 consecutive patients who underwent S-1 for refractory thymic carcinoma and correlated the clinical outcomes with potential biomarkers using paraffin-embedded cancer tissues of eight patients in the cohort.

Results: A total of 178 thymic malignancies were identified, of whom 14 patients included 12 cases of squamous cell carcinoma, one lymphoepithelioma-like carcinoma, and one undifferentiated carcinoma. Six patients exhibited a partial response (42.9 %: 95 % confidence interval [CI], 21.4-67.4) and the disease control rate was 85.7 % (60.0-96.0 %). After a median follow-up of 24.2 months, the median progression-free survival was 8.1 months (range, 2.6-12.2 months), and median overall survival was 30.0 months (range, 6.2-41.9 months). No significant correlation between biomarker expression and response was noted. However, thymidine synthase (TS)/dihydropyrimidine dehydrogenase and TS/orotate phosphoribosyltransferase were observed.

Conclusions: S-1 for refractory thymic carcinoma offered clinical activity and achieved an 85 % disease control rate. Although the biomarkers did not correlate with clinical outcome, the study results showed efficacy of S-1 as a cytotoxic chemotherapy for refractory thymic carcinoma, which warrants future investigation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / therapeutic use*
  • Biomarkers*
  • Disease Progression
  • Drug Combinations
  • Drug Resistance, Neoplasm
  • Female
  • Follow-Up Studies
  • Gene Expression
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Oxonic Acid / therapeutic use*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recurrence
  • Retrospective Studies
  • Tegafur / therapeutic use*
  • Thymus Neoplasms / diagnosis
  • Thymus Neoplasms / drug therapy*
  • Thymus Neoplasms / metabolism*
  • Thymus Neoplasms / mortality
  • Treatment Outcome
  • Young Adult

Substances

  • Antimetabolites, Antineoplastic
  • Biomarkers
  • Drug Combinations
  • RNA, Messenger
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid