A phase II randomized trial of adjuvant chemotherapy with S-1 versus S-1 plus cisplatin for completely resected pathological stage II/IIIA non-small cell lung cancer

Lung Cancer. 2018 Oct:124:255-259. doi: 10.1016/j.lungcan.2018.08.015. Epub 2018 Aug 19.

Abstract

Objectives: Platinum-based combination chemotherapy is the standard postoperative adjuvant treatment for pathological stage II/III non-small cell lung cancer (NSCLC). Oral S-1 therapy has good efficacy and relatively low toxicity for the treatment of advanced NSCLC. We investigated whether long-term S-1 monotherapy is also useful as an adjuvant therapy after surgery in patients with NSCLC.

Patients and methods: We conducted a phase II randomized open-label multi-institutional study in patients with pathological stage II/IIIA NSCLC (7th TNM classification) who underwent complete resection from 2009 to 2013. The primary endpoint, the 2-year disease-free survival (DFS) rate, was evaluated using the Bayesian method. Eligible patients were randomly assigned to two arms: oral S-1 monotherapy (S-1 arm) and S-1 plus cisplatin combination therapy followed by S-1 (S-1 plus cisplatin arm) both for a total of 1 year.

Results: A total of 70 and 71 patients were enrolled in S-1 arm and S-1 plus cisplatin arm, respectively. The 2-year DFS rates were 52% (95% confidence interval [CI], 0.40-0.63) and 61% (95% CI, 0.48-0.70) for S-1 arm and S-1 plus cisplatin arm, respectively. Both arms met the primary endpoint. Neither DFS nor OS was significantly different between the arms (log-rank test: P = 0.1695 and P = 0.8684, respectively). The main G3/4 adverse events were loss of appetite and anemia (S-1 vs. S-1 plus cisplatin: 4.3% vs. 11.6% and 0% vs. 5.8%, respectively). The treatment completion rate did not differ between the two arms (S-1 vs. S-1 plus cisplatin: 45.7%, 95% CI, 41.9-66.3% vs. 43.5% 95% CI, 44.0-68.4%).

Conclusions: Long-term adjuvant chemotherapy with S-1 was a feasible and promising treatment for patients with completely resected NSCLC, regardless of cisplatin addition. S-1 monotherapy should be investigated further, based on its low toxicity and practical convenience.

Keywords: Adjuvant chemotherapy; Cisplatin; Multicenter study; Non-small cell lung cancer; Randomized phase II trial; S-1.

Publication types

  • Clinical Trial, Phase II
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Chemotherapy, Adjuvant
  • Cisplatin / therapeutic use*
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Oxonic Acid / therapeutic use*
  • Pneumonectomy
  • Postoperative Period
  • Tegafur / therapeutic use*

Substances

  • Antineoplastic Agents
  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Oxonic Acid
  • Cisplatin