Gemcitabine and oxaliplatin in advanced biliary tract carcinoma: a phase II study

Abstract

Advanced biliary tract carcinomas (BTCs) are often diagnosed at an advanced/metastatic stage and have a poor prognosis. The combination of gemcitabine and oxaliplatin (GEMOX) has shown promising activity in this setting. This international phase II study evaluated the efficacy and safety of GEMOX as first-line therapy in patients with advanced BTCs. Eligible patients with previously untreated locally advanced or metastatic BTC received gemcitabine 1000 mg m À2 (day 1) and oxaliplatin 100 mg m À2 (day 2), every 2 weeks. Seventy patients were enroled; 72.9% had metastatic disease. Sixty-seven patients were treated. There were 10 confirmed partial responses (14.9%; 95% confidence interval (CI), 7.4 -25.7%) in the treated population (RECIST). Twenty-four patients (35.8 %) had stable disease. The objective response rate was 20.5% in patients with non-gallbladder cancers (9/44 patients) and 4.3% in patients with gallbladder cancers (1/23). Median overall survival for the intent-to-treat population was 8.8 months (95% CI, 6.9 -11.1%) and progression-free survival was 3.4 months (95% CI, 2.5 -4.6%). Grade 3/4 toxicities included thrombocytopenia (14.9% of patients), alanine aminotransferase elevation (13.4%), anaemia (10.4%), neutropenia (11.9%) and pain (11.9%). In this study, GEMOX demonstrated activity in non-gallbladder carcinoma, but poor activity in gallbladder carcinoma. GEMOX is well tolerated in advanced BTCs.

Antitumor Activity of Src Inhibitor Saracatinib (AZD-0530) in Preclinical Models of Biliary Tract Carcinomas

“…The response rates of single-agent gemcitabine range from 8% to 60%, depending on the cohort reported (3). The best result of combination chemotherapy in a phase II study was obtained for a regimen based on gemcitabine plus oxaliplatin (GEMOX), for which a 36% of response rate and 15.4 months of median survival have been achieved (4). Recently, the U.K. ABC-02 randomized phase III trial showed that the association of gemcitabine with cisplatin increased both progression-free survival (PFS) and overall survival (OS), compared with gemcitabine alone (median, 8 vs. 5 months and 11.7 vs. 8.1 months, respectively; ref.…”

Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

“…Although the combination of these drugs improves the progression-free and overall survival compared with gemcitabine alone, the median overall survival is still modestly approaching 1 year in metastatic CCA 244 . If cisplatin is contraindicated (for example, in renal insufficiency), safety and efficacy using gemcitabine in combination with oxaliplatin have been demonstrated in several phase II studies 248,249 . When gemcitabine and cisplatin fail, no established standard regimens in the second-line setting are available 250 .…”

Surgical strategy for bile duct cancer: Advances and current limitations

“…The most extensively studied agents in unresectable cholangiocarcinoma are fluorouracil (5-FU) and gemcitabine, which have been investigated as a single agent [177][178][179] and in combination with other drugs, such as mitomycin C [178] , leucovorin [180] , cisplatin [181] , capecitabine [182] , epirubicin [183] , and oxaliplatin [184] . Eckel et al [185] conducted a pooled analysis of 104 chemotherapy studies in advanced bile duct cancers, which suggested that gemcitabine combined with cisplatin or oxaliplatin resulted in the best response without significantly improved survival.…”