Phase II trial of S-1 treatment as palliative-intent chemotherapy for previously treated advanced thymic carcinoma

Cancer Med. 2020 Oct;9(20):7418-7427. doi: 10.1002/cam4.3385. Epub 2020 Aug 19.

Abstract

Thymic carcinoma (TC) is a rare cancer with minimal evidence of survival following palliative-intent chemotherapy. Sunitinib, everolimus, and pembrolizumab have been proposed as active agents based on previous phase II trials. In this phase II study, TC patients previously treated with platinum-based chemotherapy were enrolled. The patients received S-1 orally twice daily at a dose of 40-60 mg/m2 for 4 weeks, followed by 2 weeks off until the progression of the disease or the presence of unacceptable toxicities. The primary endpoint was the objective response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. The sample size of 26 patients was planned to reject the ORR of 10% under the expectation of 30% with a power of 0.80 and a type I error of 0.05 (one-sided). Twenty-six patients were recruited between 2013 and 2016; 23 patients had squamous cell carcinoma and 10 had an ECOG performance status of 0. One patient showed complete response and seven patients showed partial responses, resulting in a 30.8% response rate (90% confidence interval [CI], 18.3-46.9) and an 80.8% disease control rate (90% CI, 65.4-90.3). The median PFS was 4.3 months (95% CI, 2.3-10.3 months) and median OS was 27.4 months (95% CI, 16.6-34.3). Adverse events of grade ≥ 3 included neutropenia (12%), skin rash (8%), elevated alanine aminotransferase, and fatigue (4%). No treatment-related death was observed. S-1 confirmed clinical activity with tolerability in patients with previously treated TC. (UMIN000010736).

Keywords: S-1; chemotherapy; phase II; rare cancer; thymic carcinoma.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Drug Combinations
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Oxonic Acid / adverse effects
  • Oxonic Acid / therapeutic use*
  • Palliative Care* / methods
  • Retreatment
  • Tegafur / adverse effects
  • Tegafur / therapeutic use*
  • Thymus Neoplasms / drug therapy*
  • Thymus Neoplasms / mortality
  • Thymus Neoplasms / pathology*
  • Treatment Outcome

Substances

  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid