N. Robert has received honoraria from Roche for lectures clopidogrel and consulting and also received research support from Roche.Biliary tract cancers are relatively rare tumors with a dismal prognosis. This kind of tumor is more likely to occur in patients aged between 50 and 70 years. As far as the role of nonsurgical oncologic treatment is concerned, the only standard regimen for advanced disease has recently been established. In fact, the ABC 02 study, a practice changing phase III study, recognized thegemcitabine/cisplatin regimen as the aromatase standard of care, with a stable disease rate of 81%, progression free survival of 8 months and median overall survival of 11.7 months. Due to clinical conditions, patients who receive palliative chemotherapy are usually treated with single agent gemcitabine or with combination regimens including mitomycin or fluoropyrimidines.
Response rates with these treatments range from 10 to 35%, and median OS time varies between 5 and 12 months. Nevertheless, the small number of published trials and the considerable variability in the patients, clinical characteristics make the data difficult to interpret. High Throughput Screening Nowadays, there is no standard chemotherapy regimen in BTC. Several reports have demonstrated that gemcitabine is active in BTC. Capecitabine is an oral fluoropyrimidine carbamate that selectively generates 5 FU in tumor tissues. Gemcitabine also appears to modulate the activity of 5 fluorouracil in renal and gastrointestinal malignancies. Capecitabine offers the possibility of continuous tumor exposure to 5 FU by preferential activation at the tumor, VEGFR signaling pathway while potentially minimizing the exposure of healthy body tissues to systemic 5 FU. Moreover, 5 FU has demonstrated activity in BTC. As shown in our phase I study, to enhance the cytotoxic activity of gemcitabine, an alternative infusion regimen has been explored.
As the active metabolite of gemcitabine, 2 ,2 difluorodeoxycytidine triphosphate, has a long intracellular half life, a fixed dose rate infusion of 10 mg/m 2 /min has been shown to lead to maximal intracellular accumulation. In particular, it has been demonstrated that increasing the infusion time while holding the dose rate constant at 10 mg/ m 2 /min could result in increased intracellular levels of dFdCTP, thus enhancing the activity of gemcitabine. On the basis of phase I results, the dose of FDR gemcitabine 800 mg/m 2 in 80 min on days 1 and 8 plus capecitabine 650 mg/m 2 b.i.d, for 14 consecutive days followed by 1 week of rest, is a recommended schedule that we used in this study. This is a phase II study evaluating toxicity, response, and survival associated with using a combination of FDR gemcitabine and capecitabine to treat patients with unresectable or metastatic BTCs. Patients and Methods Eligibility Patients with histologically confirmed unresectable or metastatic BTC adenocarcinomas, including those who were at least 18 years old and who had an Eastern Cooperative Oncology Group performance status 1, were considered suitable for the study. The following hematologic and chemistry parameters were recommended: absolute neutrophil count 1,500/mm 3, platelet count 100,000/mm 3, hemoglobin 10.0 g/100 ml, preserved renal function, and hepatic function.