Multicenter Phase II Study of Oxaliplatin, Irinotecan, and S-1 as First-line Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer.
- Author:
Changhoon YOO
1
;
Boram HAN
;
Hyeong Su KIM
;
Kyu pyo KIM
;
Deokhoon KIM
;
Jae Ho JEONG
;
Jae Lyun LEE
;
Tae Won KIM
;
Jung Han KIM
;
Dae Ro CHOI
;
Hong Il HA
;
Jinwon SEO
;
Heung Moon CHANG
;
Baek Yeol RYOO
;
Dae Young ZANG
Author Information
- Publication Type:Multicenter Study ; Original Article
- Keywords: Biliary tract neoplasms; Cholangiocarcinoma; Chemotherapy; Irinotecan; Oxaliplatin; S-1
- MeSH: Biliary Tract Neoplasms*; Biliary Tract*; Cholangiocarcinoma; Cisplatin; Diarrhea; Disease-Free Survival; Drug Therapy; Drug Therapy, Combination; Exome; Humans; Male; Neutropenia; Peripheral Nervous System Diseases; Prognosis; Triplets
- From:Cancer Research and Treatment 2018;50(4):1324-1330
- CountryRepublic of Korea
- Language:English
- 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 patientswith histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study. Patients received 65 mg/m2 oxaliplatin (day 1), 135 mg/m2 irinotecan (day 1), and 40 mg/m2 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.
