Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced BTC based on the success of the ABC-02 trial, the overall prognosis is still poor as median survival of less than 1 year. Therefore, we investigated novel combination of three drugs including oxaliplatin, irinotecan and S-1, oral fluoropyrimidine, (OIS) for advanced BTC.
Chemotherapy-naïve patients with histologically documented unresectable or metastatic BTC were eligible for this study. Patients received oxaliplatin 65 mg/m2 Day 1, irinotecan 135 mg/m2 Day 1, and S-1 40 mg/m2 BID Day 1-7, every 2 weeks, until the disease progression or intolerable toxicities. Primary endpoint was objective response rate (ORR) defined by RECIST v1.1 and secondary endpoints include progression-free survival (PFS), overall survival (OS) and safety profile. According to the Simon’s optimal two-stage design with type 1 error of 0.05 and a power of 80%, 31 patients were needed with a hypothesis of improving ORR from 20% to 35%.
Between October 2015 and June 2016, a total of 32 patients were enrolled in two referral institutes in Korea. Median age was 64 years (range 40-76) and 24 (75%) patients were male. All but one patient (97%) had metastatic or recurrent disease. Intrahepatic lesion is the most common primary tumor site (n = 13, 41%) and followed by gallbladder (n = 11, 34%) and extrahepatic lesion (n = 8, 25%). With median follow-up duration of 10.1 months, patients received median 12 cycles (range, 1-21) of study treatment. ORR was 50% as partial response was achieved in 16 patients. Median PFS was 7.1 months (95% CI, 5.3-8.8) and median OS was not reached. The 1-year PFS and OS rates were 25% and 59%, respectively. Most common grade 3-4 adverse events were neutropenia (n = 10, 32%), followed by diarrhea (n = 2, 6%) and peripheral neuropathy (n = 2, 6%).
OIS triplet combination chemotherapy was feasible and showed promising efficacy outcomes as first-line treatment in patients with advanced BTC. Randomized trial is needed to validate the efficacy of this triplet regimen.
Clinical trial identification
Legal entity responsible for the study
Hallym University Medical Center and Asan Medical Center
All authors have declared no conflicts of interest.