Phase I study of neoadjuvant S-1 plus cisplatin with concurrent radiation for biliary tract cancer (KOBTC02).

Abstract

353 Background: Although surgery plays a key role in the curative treatment for biliary tract cancer (BTC), the prognosis is not satisfactory because of frequent postoperative recurrence. Multimodal treatment has been warranted in order to improve this situation. The aim of this study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of cisplatin as neoadjuvant chemoradiotherapy with S-1 and external beam radiation for BTC. Methods: Patients with resectable BTC at initial diagnosis were eligible for inclusion. The planned dosages of cisplatin (mg/m2)/S-1 (mg/m2/day) were as follows: 40/80 (level 0); 50/80 (level 2); 60/80 (level 3). S-1 was orally administered twice daily from day 1 to 14 and day 29 to 42. Cisplatin was administered intravenously over 2 hours in each dosage of level at day 1 and 29. Radiation was delivered as a total dose of 50.4 Gy (28 fractions to 1.8 Gy). Dose-limiting toxicity (DLT) was a delay factor of the schedule due to incomplete recovery. (Response rate (RR) was evaluated according to the RECIST version 1.0.). Results: Twelve patients were enrolled, and level 1 was chosen as the starting dose. One of six patients developed DLTs at level 1, and the dose was escalated to level 2. DLTs occurred in two of six patients at level 2. As the MTD were determined as over 60 mg/m2, the RD were confirmed as level 2 for a subsequent phase II study. Conclusions: We determined the MTD and RD of cisplatin with concurrent S-1 and external beam radiation as neoadjuvant chemoradiotherapy for resectable BTC. Although further clinical trials are warranted to evaluate efficacy, this new regimen is potentially expected to become a standard neoadjuvant treatment for resectable BTC. Clinical trial information: 000009028.