Phase I study of neoadjuvant S‐1 plus cisplatin with concurrent radiation for biliary tract cancer (Tokyo Study Group for Biliary Cancer: TOSBIC02)

• Published in: Annals of gastroenterological surgery 2023-09, Vol.7 (5), p.808-818
• Main Authors: Abe, Yuta, Itano, Osamu, Takemura, Yusuke, Minagawa, Takuya, Ojima, Hidenori, Shinoda, Masahiro, Kitago, Minoru, Obara, Hideaki, Shigematsu, Naoyuki, Kitagawa, Yuko
• Format: Article
• Language: English
• Subjects: biliary tract neoplasm; Cancer therapies; chemoradiotherapy; Chemotherapy; Cholangiocarcinoma; clinical trial Phase I; Creatinine; Drug dosages; Lymphatic system; Magnetic resonance imaging; neoadjuvant therapy; Neutropenia; Original; Patients; postoperative complications; Potassium; Radiation; Registration; Review boards; Surgery; Toxicity
• ISSN: 2475-0328; 2475-0328
• DOI: 10.1002/ags3.12682

Aim Neoadjuvant chemoradiotherapy may improve survival in patients with advanced cholangiocarcinoma. This Phase I study aimed to determine the recommended dose of neoadjuvant chemoradiotherapy and decide whether to move to a Phase II study. Methods Patients diagnosed with resectable stage II–IVa cholangiocarcinoma were administered cisplatin (40 [level 0], 50 [level 1 as starting dose], or 60 [level 2] mg/m2), 80 mg/m2 of S‐1, and 50.4 Gy of external beam radiation. The recommended dose was defined as a dose one‐step lower than the maximum‐tolerated dose, which was defined when dose‐limiting toxicity was observed in three or more of the six patients. Results Twelve patients were eligible from November 2012 to May 2016. Ten patients had perihilar cholangiocarcinoma and two patients had distal cholangiocarcinoma. Dose‐limiting toxicity was observed in one of the first six patients at level 1 and two of the next six patients at level 2; thus, the maximum‐tolerated dose was not determined even at level 2 and the recommended dose was determined as level 2. Four patients had partial response, four patients had stable disease, and two patients had progression of disease because of liver metastases. Finally, nine patients underwent radical surgery and seven cases achieved R0 resection. However, five cases suffered biliary leakage and one suffered intrahospital death due to rupture of the hepatic artery. Conclusion We determined the recommended dose of neoadjuvant chemoradiotherapy for resectable cholangiocarcinoma. However, we terminated the trial due to a high incidence of morbidity and unexpected mortality. A prospective Phase I study was conducted to explore the recommended dose of NACRT using S‐1 and cisplatin combined with concurrent radiation for the treatment of advanced resectable biliary tract cancer. We determined the recommended dose of NACRT. Although part of them had effective pathological responses, we finally terminated the trial due to a high incidence of morbidity and unexpected mortality.