Adjuvant treatment of resectable biliary tract cancer with cisplatin plus gemcitabine: A prospective single center phase II study

Abstract

BackgroundBiliary tract cancer (BTC) is a dismal disease, even after curative intent surgery. We conducted this prospective, non-randomized phase II study to evaluate the feasibility and efficacy of cisplatin and gemcitabine as adjuvant treatment in patients with resected BTC.MethodsPatients initially received gemcitabine 1000 mg/m2 alone on days 1, 8 and 15 every 28-days for a total of six cycles (single agent cohort), and after protocol amendment a combination therapy with gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 was administered every 21 days for a total of eight cycles (combined regimen cohort). Treatment was planned to start within eight weeks after curative intent resection. Adverse events, disease-free survival and overall survival were assessed.ResultsOverall 30 patients were enrolled in the study from August 2008 and last patient was enrolled at 2nd December 2014. The follow-up of the patients ended at 31st December 2016. The first 9 patients received single-agent gemcitabine. The interim analysis met the predefined feasibility criteria and, from September 2010 on, the second group of 21 patients received the combination of cisplatin plus gemcitabine. In the single-agent cohort with gemcitabine the median relative dose intensity (RDI) was 100% (IQR 88.3–100). Patients treated with the combination cisplatin-gemcitabine received an overall median RDI of 100% (IQR 50–100) for cisplatin and 100% (IQR 75–100) for gemcitabine respectively. The most significant non-hematological adverse events (grade 3 or 4) were fatigue (20%), infections during neutropenia (10%), and two cases of biliary sepsis (7%). Abnormal liver function was seen in 10% of the patients. One patient died due to infectious complications during treatment with cisplatin and gemcitabine. The median disease-free survival (DFS) was 14.9 months (95% CI 0–33.8) with a corresponding 3-year DFS of 43.1 ± 9.1%. The median overall survival (OS) was 40.6 months (95% CI 18.8–62.3) with a 3-year OS of 55.7 ± 9.2%. No statistically significant differences in survival were seen between the two treatment cohorts.ConclusionAdjuvant chemotherapy with gemcitabine with or without cisplatin was well tolerated and resulted in promising survival of the patients.Trial registrationThe study was retrospectively registered on 25th June 2009 at clinicaltrials.gov (NCT01073839).

Effect of Hyperthermic Intraperitoneal Perfusion Chemotherapy Combined with Radical Surgery and Capecitabine on Stage III Gallbladder Cancer

“…e current chemotherapeutic drugs used in gallbladder cancer include platinum, gemcitabine, fluorouracil, etc. [9,10]. HIPEC has achieved unique effects in the treatment of peritoneal cancer (PC).…”

Evaluation of positive ductal margins of biliary tract cancer in intraoperative histological examination

“…Some report showed the benefit of disease-free survival (39), but the evidence is insufficient due to the small number (<10) of 5-year survivors and retrospective study (38). Moreover, some reports have revealed the effectiveness of chemotherapy for biliary tract cancer (40). However, adjuvant chemotherapy for biliary tract cancer has not been investigated.…”

“…Prospective studies are needed. A large multi-national study (ACTICCA-1) is evaluating the combination of gemcitabine plus cisplatin for adjuvant chemotherapy with results expected within the next years (40,43).…”

Treatment of biliary tract carcinoma over the last 30 years

“…Given that GEM/CDDP has been the standard firstline treatment for patients with unresectable biliary tract carcinoma as indicated in the ABC-02 trial (7), GEM/ CDDP should be effective as adjuvant chemotherapy as well. A non-randomized small cohort phase II study indicated the promising survival of patients undergoing curative resection for biliary tract carcinoma (43). Moreover, a multicenter, open-label, randomized phase III trial on the efficacy of adjuvant GEM/CDDP is underway (44).…”