Oxaliplatin, fluorouracil and leucovorin for advanced biliary system adenocarcinomas: a prospective phase II trial

Abstract

We studied the activity of combined oxaliplatin and fluorouracil-leucovorin in 16 consecutive patients with advanced biliary tract adenocarcinomas. The disease control rate (responses and stable disease) was 56% (95% confidence interval, 29 -84%) and the median overall survival time was 9.5 months (range 0.9 -26.8+). Therefore, this regimen might be active in biliary adenocarcinomas with further evaluation necessary. While surgery currently provides the only curative treatment option in tumours of the biliary system, the majority of patients is diagnosed with advanced stages of disease. Patients with stage IV (UICC) gallbladder carcinoma with distant metastases or with unresectable biliary carcinomas only treated by best supportive care, have a poor prognosis with a median survival time of less than 3 months (Pitt et al, 1997;Hejna et al, 1998).However, in these tumour entities, palliative chemotherapy with single agents or combination therapies result in partial responses in about 10 to 20% of patients (Hejna et al, 1998). Moreover, innovative treatment modalities other than chemotherapy like photodynamic therapy have yielded preliminary beneficial results only in local tumour control but not for metastatic disease (Ortner et al, 1998). External beam radiation and brachytherapy have only demonstrated efficacy in individual patients (Hejna et al, 1998).Based on the preclinical evidence that oxaliplatin combined with 5-FU-LV possesses remarkable synergistic cytotoxicity in various human malignancies (Raymond et al, 1997), this prospective phase II trial was initiated to investigate for the first time, to the best of our knowledge, the activity and safety profile of this combination therapy for advanced biliary system adenocarcinomas. PATIENTS AND METHODSThis prospective multicentre study enrolled 16 consecutive patients with histologically or cytologically confirmed adenocarcinomas of the gallbladder or the intrahepatic or extrahepatic biliary tract between November 1997 and May 2001. All patients had locally advanced, unresectable or metastatic disease and fulfilled the standard eligibility criteria (Raderer et al, 1999). The trial protocol was approved by the ethics committee of the University of Tübingen, and written consent was obtained from all patients before study entry.The patients received the 2 weekly administered FOLFOX 3 regimen (André et al, 1998) including l-OHP 85 mg m 72 per 2 h on day 1 concurrent with LV 500 mg m 72 per 2 h, followed by continuous 5-FU infusion 1.5 to 2.0 g m 72 per 22 h on days 1 -2. Objective tumour evaluation for response was performed at 9 week intervals according to WHO standard criteria (World Health Organization, 1979). StatisticsOverall survival (OS) was calculated from the initiation of chemotherapy until death. Time to progression (TTP) was determined by the interval between the start of chemotherapy and the date of objectively measured disease progression, or the occurence of death by any cause. Statistical analysis was performed using SPSS for Windows 10.0 (SPSS, In...

The cisplatin, epirubicin, 5‐fluorouracil, gemcitabine (PEFG) regimen in advanced biliary tract adenocarcinoma

“…Fifty-two percent of patients had a 50% decrease in CA 19-9 concentration compared with baseline, 19% of patients had a PFS >12 months, and the median survival was 12.1 months. These results compare favorably with reported ORRs between 10% and 45% 22,27-33 and a median survival between 8 months and 11 months 22,[27][28][29][30][31][32][33] observed in the majority of reported clinical trials that included 2-drug combinations. The role of chemotherapy in advanced biliary tract cancer remains to be defined, and no standard regimen has been identified.…”

“…[17][18][19][20] Different combination chemotherapy regimens containing gemcitabine, anthracyclines, platinum analogs, S1, fluoropyrimidines, and mitomycin C reportedly produced ORRs between 15% and 45%, a median survival of 6 to 11 months, and a 1-year survival rate that ranged from 20% to 40%. [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] The combined regimen of cisplatin, epirubicin, FU, and gemcitabine (PEFG) is an effective, upfront treatment for advanced pancreatic cancer. 38,39 Because this combination regimen contains the most active drugs commonly administered in the therapeutic approach of biliary tract cancer, we decided to assess its activity against BTA.…”

Capecitabine plus oxaliplatin as first-line treatment in patients with advanced biliary system adenocarcinoma: a prospective multicentre phase II trial

“…The disease control rate (responses and stable disease (SD)) was 56%, and the median OS was 9.5 months (Nehls et al, 2001). To improve efficacy and to offer a more convenient treatment option for patients by reducing clinical visits and avoiding indwelling devices, we prospectively investigated the activity and toxicity profile of three-weekly intravenous oxaliplatin plus oral capecitabine (CAPOX) in two stratified cohorts with either advanced GBC and ECC (group A) or advanced ICC (group B).…”

Outpatient chemotherapy with gemcitabine and oxaliplatin in patients with biliary tract cancer

“…For this drug objective response rates (RR) in a range from 8 to 60% have been reported Valencak et al, 1999;Gallardo et al, 2001;Gebbia et al, 2001;Kubicka et al, 2001;Penz et al, 2001). In addition, various combination therapies have been investigated in the setting of phase II studies with RRs between 9.5 and 53% (Gebbia et al, 2001;Patt et al, 2001;Doval et al, 2002;Kuhn et al, 2002;Nehls et al, 2002;Taieb et al, 2002;Kornek et al, 2004;Patt et al, 2004;Alberts et al, 2005;Ducreux et al, 2005). Overall, most favourable RRs in BTC were reached with protocols that combine cisplatin (CDDP) with 5-fluorouracil or GEM (Doval et al, 2002;Taieb et al, 2002;Ducreux et al, 2005).…”