Phase I study of adjuvant chemotherapy with gemcitabine plus cisplatin in patients with biliary tract cancer undergoing curative resection without major hepatectomy (KHBO1004).

Purpose: We conducted a phase I study to determine the maximum tolerated dose and recommended dose (RD) of this gemcitabine plus cisplatin (GC) combination in the adjuvant setting for biliary tract cancer (BTC). GC has become a standard chemotherapy regimen for patients with locally advanced or metastatic BTC; however, the benefit of adjuvant therapy for BTC is unclear.

Methods: Patients with BTC were eligible if they met the following criteria: Stage IB or higher; and undergoing resection without major hepatectomy. The starting dose matched the standard dose of gemcitabine (1,000 mg/m(2)) and cisplatin (25 mg/m(2)) on days 1 and 8, every 3 weeks for up to 24 weeks. The dose limiting toxicities (DLTs) were determined during the first 6 weeks, and a 3+3 dose finding design with cohorts of 3-6 patients was used. Further cohort expansion took place.

Results: One DLT, namely grade 4 neutropenia, was observed among six patients at the starting dosages. Then, we expanded the cohort with a total of eighteen patients to evaluate RD and no further DLTs were observed. During the entire study, the most common grade 3/4 adverse events were neutropenia (94 %) and leucopenia (56 %). Non-hematological toxicities were manageable.

Conclusions: We defined the standard dose of GC as the RD for adjuvant chemotherapy for BTC treated by curative resection without major hepatectomy. Further study is warranted to clarify the safety and efficacy of this regimen for all patients.