Phase II study of S-1 plus bevacizumab combination therapy for patients previously treated for non-squamous non-small cell lung cancer

Cancer Chemother Pharmacol. 2017 Jun;79(6):1215-1220. doi: 10.1007/s00280-017-3321-x. Epub 2017 Apr 28.

Abstract

Purpose: To assess the efficacy and toxicity of S-1 and bevacizumab combination therapy for patients previously treated for advanced non-squamous non-small cell lung cancer (NSCLC).

Methods: This was a prospective, multi-center, single-arm phase II study. Patients with non-squamous NSCLC who had experienced progression after cytotoxic chemotherapy were enrolled. Oral S-1 was administered on days 1-14 of a 21-day cycle, and bevacizumab (15 mg/kg) was given intravenously on day 1. Patients received S-1 adjusted on the basis of their creatinine clearance and body surface area. The primary endpoint was response rate (RR); secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety.

Results: We enrolled 30 patients. One patient had never received platinum-based therapy. Five patients had activating mutations of the epidermal growth factor receptor gene, of whom four had received tyrosine kinase inhibitors before this study. The RR was 6.7% [95% confidence interval (CI) 1.8-21.3%], and the disease control rate (DCR) was 80% (95% CI 62.7-90.5%). Median PFS was 4.8 months (95% CI 2.7-6.4 months], and median OS was 13.8 months (95% CI 8.4 months-not applicable). Patients did not experience any Grade 4 toxicity or treatment-related death. Grade 3 hematologic toxicity (anemia) occurred in one patient (3.3%). The main Grade 3 non-hematologic toxicities were anorexia (10%), infection (10%), and diarrhea (6.7%).

Conclusion: The addition of bevacizumab to S-1 was tolerable, but not beneficial for patients with previously treated non-squamous NSCLC. We do not recommend further study of this regimen.

Keywords: Bevacizumab; Combination chemotherapy; Non-squamous non-small cell lung cancer; Phase II; S-1.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Angiogenesis Inhibitors / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Disease-Free Survival
  • Drug Combinations
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Male
  • Middle Aged
  • Oxonic Acid / administration & dosage
  • Prospective Studies
  • Tegafur / administration & dosage
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Drug Combinations
  • S 1 (combination)
  • Tegafur
  • Bevacizumab
  • Oxonic Acid