Biliary 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.
Patients 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.
Overall 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.
Adjuvant chemotherapy with gemcitabine with or without cisplatin was well tolerated and resulted in promising survival of the patients.
The study was retrospectively registered on 25th June 2009 at clinicaltrials.gov (NCT01073839).
Burris HA 3rd, Moore MJ, Andersen J, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol Off J Am Soc Clin Oncol. 1997;15(6):2403–13. CrossRef
Kubicka S, Rudolph KL, Tietze MK, Lorenz M, Manns M, Phase II. Study of systemic gemcitabine chemotherapy for advanced unresectable hepatobiliary carcinomas. Hepato-Gastroenterology. 2001;48(39):783–9. PubMed
Dover LL, Oster RA, McDonald AM, DuBay DA, Wang TN, Jacob R. Impact of adjuvant chemoradiation on survival in patients with resectable cholangiocarcinoma. HPB (Oxford). 2016;18(10):843–50. CrossRef
Cho M, Wang-Gillam A, Myerson R, et al. A phase II study of adjuvant gemcitabine plus docetaxel followed by concurrent chemoradation in resected pancreaticobiliary carcinoma. HPB (Oxford). 2015;17(7):587–93. CrossRef
Stein A, Arnold D, Bridgewater J, et al. Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1 trial) - a randomized, multidisciplinary, multinational phase III trial. BMC Cancer. 2015;15:564. CrossRefPubMedPubMedCentral
Edeline J, Bonnetain F, Phelip J, et al. Gemox versus surveillance following surgery of localized biliary tract cancer: Results of the PRODIGE 12-ACCORD 18 (UNICANCER GI) phase III trial. J Clin Oncol. 2017;35(suppl 4S; abstr 225)
BILCAP. A randomized clinical trial evaluating adjuvant chemotherapy with capecitabine compared to expectant treatment alone following curative surgery for biliary tract cancer. J Clin Oncol. 2011;29(suppl; abstr 4125):4125.
Primrose J, Fox R, Palmer D, et al. Adjuvant capecitabine for biliary tract cancer: The BILCAP randomized study. J Clin Oncol. 2017;35(suppl; abstr 4006):4006.
- Adjuvant treatment of resectable biliary tract cancer with cisplatin plus gemcitabine: A prospective single center phase II study
Alexander R. Siebenhüner
- BioMed Central
Neu im Fachgebiet Onkologie
Mail Icon II