Efficacy and Safety of S-1 Monotherapy in Patients with Advanced Biliary Tract Adenocarcinoma

Abstract

Aim: We investigated the efficacy and safety of S-1 monotherapy for the treatment of advanced biliary tract adenocarcinoma (BTA) in a clinical practice setting. Methods: We reviewed clinical data from 217 patients with advanced BTA who were treated with S-1 monotherapy between August 2004 and September 2007. Results: 162 eligible patients were identified. The primary tumors were intrahepatic (n = 57), in the gall bladder (n = 50), in extrahepatic bile ducts (n = 41) and in the ampulla of Vater (n = 14). Sixteen of 120 assessable patients achieved partial responses, with a response rate of 13.3% (95% CI 7.2–19.4%). Another 51 patients had stable disease, with an overall tumor control rate of 55.8% (95% CI 46.9–64.7%). The median time to progression was 2.7 months and the median overall survival time was 6.9 months. Response rates and survival differed significantly according to the primary site of the tumor (p = 0.002 and p < 0.001, respectively), with extrahepatic bile duct adenocarcinoma having the best prognosis. The treatment regimen produced only mild toxicity in most cases (grade 1 or 2), even for patients with hyperbilirubinemia. Conclusion: S-1 has a favorable toxicity profile and can be safely administered to BTA patients with hyperbilirubinemia. The efficacy of S-1 against advanced BTA depends on the tumor site and is most effective in patients with extrahepatic BTA.

Multicenter phase II study of S-1 monotherapy as second-line chemotherapy for advanced biliary tract cancer refractory to gemcitabine

“…The efficacy and safety of S-1 monotherapy have previously been reported in the setting of first-line chemotherapy [12][13][14]. Only our singlecenter feasibility study has investigated S-1 for second-line chemotherapy of advanced BTC [15].…”

Randomised phase II trial of photodynamic therapy plus oral fluoropyrimidine, S-1, versus photodynamic therapy alone for unresectable hilar cholangiocarcinoma

“…Based on the body surface area, S-1 was administered if <1.25 m 2 , 80 mg/day; if 1.25-1.5 m 2 , 100 mg/day; if P1.5 m 2 , 120 mg/day. S-1 was administered orally twice daily for 14 days, followed by 7 days without treatment [17]. The severity of adverse events of S-1 was determined using common terminology criteria for adverse events (CTCAE) version 4.0.…”

“…Oxo may reduce the serious gastrointestinal side-effects of 5-FU, as it prevents the phosphorylation of 5-FU in the gastrointestinal tract by inhibiting orotate phosphoribosyl transferase [16]. S-1 has a favourable toxicity profile and can be safely administered to biliary tract cancer patients with hyperbilirubinemia [17]. Therefore, interval PDT with S-1, which is theoretically feasible, may be convenient for patients with UHC compared with other intravenous systemic chemotherapy regimens.…”

A phase I study of S-1 treatment with a 3 week schedule in advanced biliary cancer patients with or without hepatic dysfunction

“…S-1 was also shown to be an active agent in previous studies [8,9]. Recently, the combination of gemcitabine and cisplatin improved OS and PFS by 30% over gemcitabine alone [29] and has become a new standard of care in patients with advanced biliary tract cancer.…”

“…Phase II trials have demonstrated that S-1, as a single agent, is active for the treatment of gastric, colorectal, head and neck, nonsmall cell lung, and pancreatic cancer [2][3][4][5][6][7]. S-1 was also effective in the treatment of patients with advanced biliary tract adenocarcinoma and had a favorable toxicity profile [8,9]. A phase I study of S-1 in a Japanese population defined dosage for the early phase II study of 75 mg/body twice daily for 28 consecutive days, followed by a 14-day rest (1 course) [10].…”