Cancer Research and Treatment

The Korean Cancer Association (대한암학회)
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Multicenter Phase II Study of Oxaliplatin, Irinotecan, and S-1 as First-Line Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer

  • Yoo, Changhoon (Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Han, Boram (Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine) ;
  • Kim, Hyeong Su (Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine) ;
  • Kim, Kyu-pyo (Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Deokhoon (Asan Institute for Life Science, University of Ulsan College of Medicine) ;
  • Jeong, Jae Ho (Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Lee, Jae-Lyun (Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Tae Won (Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Kim, Jung Han (Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine) ;
  • Choi, Dae Ro (Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine) ;
  • Ha, Hong Il (Department of Radiology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine) ;
  • Seo, Jinwon (Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine) ;
  • Chang, Heung-Moon (Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Ryoo, Baek-Yeol (Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine) ;
  • Zang, Dae Young (Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine)
  • Received : 2017.10.31
  • Accepted : 2018.01.04
  • Published : 2018.10.15
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Abstract

Purpose Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC), overall prognosis remains poor. We investigated the efficacy of a novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC. Materials and Methods Chemotherapy-naive patients with histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study. Patients received $65mg/m^2$ oxaliplatin (day 1), $135mg/m^2$ irinotecan (day 1), and $40mg/m^2$ S-1 (twice a day, days 1-7) every 2 weeks. Primary endpoint was objective response rate. Targeted exome sequencing for biomarker analysis was performed using archival tissue. Results In total, 32 patients were enrolled between October 2015 and June 2016. Median age was 64 years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had metastatic or recurrent disease. Response rate was 50%, and median progression-free survival and overall survival (OS) were 6.8 months (95% confidence interval [CI], 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent genomic alterations (42% and 32%, respectively), and KRAS mutations showed a marginal relationship with worse OS (p=0.07). Conclusion OIS combination chemotherapy was feasible and associated with favorable efficacy outcomes as a first-line treatment in patients with advanced BTC. Randomized studies are needed to compare OIS with gemcitabine plus cisplatin.

Keywords

Acknowledgement

Supported by : Hallym University, Asan Institute for Life Sciences

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