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

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347 Background: GC has become a standard chemotherapy for patients with locally advanced or metastatic BTC. The benefit of adjuvant therapy for BTC is unclear, however, it is used worldwide due to BTC’s dismal prognosis. We conducted a phase I study for adjuvant chemotherapy with GC in patients with BTC in order to determine the maximum-tolerated dose (MTD) and recommended dose (RD). Methods: Patients with BTC were eligible if they met the following criteria: Stage IB or higher; undergoing resection without major hepatectomy; over 20 years of age; ECOG PS 0-1; adequate organ functions. The starting dose (Level 1) of GC was the same as the standard dose of advanced disease and dose was planned to adjust, using a 3+3 design with cohorts of 3-6 patients and further cohort expansion took place. The Dose Limiting Toxicities (DLTs) were determined during the first six weeks and RD was determined through the entire treatment. Results: One DLT out of 6 patients, with grade 4 neutropenia, was observed at Level 1 and an expanded cohort was further examined. A total of eighteen patients were enrolled and one DLT was observed as described above. During the first six weeks, the most common grade 3 or 4 related adverse events were neutropenia (n=10: 56%) and leukopenia (n=6: 33%). Through the entire treatment, non-hematologic toxicities were manageable. Seven (39%) patients completed the protocol treatment, seven (39%) dropped off due to the need of second time dose reduction, two didn’t meet starting criteria of creatinin with grade 1 increase in CTCAE, one had rapid tumor progression died within 30 days after the last administration of GC and one withdrew after reporting dead case. Conclusions: A standard dose of GC might be feasible for adjuvant chemotherapy for BTC undergoing curative resection without major hepatectomy. We selected standard dose of GC as RD for a subsequent phase II study. Clinical trial information: NCT01297998.