S-1 monotherapy as first-line treatment in patients with advanced biliary tract cancer: a multicenter phase II study

Abstract

A pilot phase II study showed S-1 monotherapy to be safe and active against biliary tract cancer (BTC). We, therefore, conducted a multicenter phase II study to evaluate the antitumor effect and safety of S-1 in previously untreated patients with advanced BTC. Eligible patients had pathologically proven, unresectable adenocarcinoma with no prior chemotherapy or radiotherapy. Patients received S-1 orally at 80 mg/m2 total daily dose divided b.i.d. for 28 days followed by 14 days of rest. Of the 41 enrolled patients, 40 were assessable. The primary tumor sites were as follows: gallbladder (n = 20), extrahepatic bile duct (n = 15), and the ampulla of Vater (n = 5). One patient (2.5%) achieved a complete response, 13 patients (32.5%) had partial responses, 17 patients (42.5%) had no change, 7 patients (17.5%) had progressive disease, and 2 patients (5.0%) were not evaluable. The overall objective response rate was 35.0%. The median overall survival (median OS) was 9.4 months, and the median time to progression was 3.7 months. Grade 3 or 4 toxicities included fatigue (7.5%), anorexia (7.5%) and T-Bil elevation (7.5%). Significant antitumor activity combined with a mild toxicity profile was observed. This monotherapy warrants further evaluation in a randomized study.

Rational therapeutic strategy for T2 gallbladder carcinoma based on tumor spread

“…A low level of DPD and TS activity, and a high level of OPRT activity enhance the antitumor effect of S-1 [51] . A phase Ⅱ study of S-1 in biliary tract cancer has shown promising results with a response rate of 21%-35% [27,28] , and S-1 can be expected to have a good effect on gallbladder cancer. In T2 GBCa, ss mas cancers showed a high rate of recurrence, regardless of the radical surgical approach.…”

“…S-1 is an oral anticancer drug that contains two biochemical modulators, 5-chloro-2,4-dihydroxypridine and potassium oxonate, which improve the tumor-selective toxicity of 5-fluorouracil (5-FU) [26] . A phase Ⅱ study of S-1 has shown promising results with response rates ranging from 21% to 35% in biliary tract cancer [27,28] .…”

Clinical practice guidelines for the management of biliary tract cancers 2015: the 2nd English edition

“…S-1 is also approved according to the results of phase II trials [216,217]. In addition, the combination therapy of gemcitabine and S-1 shows benefits in several phase II studies [218][219][220][221] and a phase III study is now being conducted.…”

Targeted therapy for biliary-tract cancer

“…A number of studies have investigated the usefulness of gemcitabine alone or tegafur/gimeracil/oteracil potassium (S-1) alone, and also gemcitabine-based combination regimens (Table 1) [5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. Based on the results of phase II studies, the Japanese guideline for biliary tract and ampullary carcinomas recommends gemcitabine alone or S-1 alone as the first line chemotherapy [23].…”