Gemcitabine, 5‐fluorouracil, and leucovorin in advanced biliary tract and gallbladder carcinoma

Abstract

BACKGROUNDGemcitabine has broad activity in a variety of solid tumors including biliary tract carcinomas. The authors evaluated 6‐month survival, response, and toxicity associated with a combination of gemcitabine, 5‐fluorouracil (5‐FU), and leucovorin (LV) in patients with unresectable or metastatic biliary tract or gallbladder adenocarcinoma (ACA).METHODSA 4‐week course included 1000 mg/m2 gemcitabine by intravenous infusion over 30 minutes on Days 1, 8, and 15, 25 mg/m2 LV by intravenous push, and 600 mg/m2 5‐FU by intravenous push after LV.RESULTSForty‐two patients were enrolled in 6 months, 35 of whom had metastatic disease. Patients with biliary tract ACA included 24 with hepatic disease (19 patients had intrahepatic disease and 5 patients had extrahepatic disease) and 4 with disease in the ampulla of Vater. All patients were evaluable and received a median of 4 courses of treatment (range, 1–21 courses). Commonly occurring severe toxicity (NCI CTC Grade 3 or worse) included: dyspnea (four patients), nausea (four patients), fatigue (seven patients), thrombocytopenia (six patients), emesis (four patients), and diarrhea (four patients). Five partial responses (9.5%) occurred, 3 of which were sustained for ≥ 8 weeks. No treatment‐related deaths occurred. Thirty‐two patients had disease progression and 38 died after a median follow‐up of 20 months (range, 1.4–24 months). The median time to disease progression was 4.6 months (95% confidence interval [95% CI], 2.4–6.6%). The median survival period was 9.7 months (95% CI, 7–12%).CONCLUSIONSThis combination regimen was manageable in patients with advanced biliary tract and gallbladder ACA. Of 42 patients, 24 (57%) survived ≥ 6 months, satisfying the primary end point of the trial. The length of survival suggested that gemcitabine, 5‐FU, and LV had benefit equivalent to gemcitabine alone. Cancer 2005. © 2004 American Cancer Society.

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.…”

“…Conversely, nonhematologic toxicity appears to be less frequent with the PEFG regimen compared with other gemcitabine-based regimens (hand-foot syndrome, 3% vs 9%; peripheral neuropathy, 0% vs 7%-14%). 6,22,28,31,32 In pancreatic cancer, a modified PEFG regimen produced reductions in hospital admissions and toxicity without compromising activity. 43,44 The regimen's manageability and patient compliance may be improved further by substituting FU with oral fluoropyrimidines, which can overcome catheter-related risks without compromising treatment activity.…”

“…[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.…”

Adjuvant chemoradiation therapy in gallbladder cancer

“…Traditionally, 5-fluorouracil-based chemotherapy regimen has been used as an adjuvant therapy for biliary tract malignancies including GB cancer [6,9,20,21]. Recently, gemcitabine-, capecitabine, or S-1-based regimens have been tried, and several studies have demonstrated somewhat promising results from GB cancer [22][23][24][25][26]. However, few comparative analyses of treatments between detailed TNM stages of GB cancer have been reported.…”

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

“…The relatively higher response rates in the latter study as compared to our data may reflect the use of a different evaluation system (RECIST versus WHO criteria). In addition, accumulating data suggest that GBC in comparison to ICC responds noticeably better to various cytotoxic protocols (Table 5) (Kim et al, 2003;André et al, 2004;Patt et al, 2004;Alberts et al, 2005). These differences may reflect site-related distinct biologic features (Jarnagin et al, 2006).…”