Due to the small number of patients and the inclusion of all biliary types in this study, these results cannot be translated in clinical practice. A larger randomized phase III trial of  MG-132 our combination regimen compared with gemcitabine plus cisplatin needs to be conducted to validate the efficacy of FDR gemcitabine plus capecitabine in metastatic/advanced BTC patients. Several trials are ongoing with the aim to explore the activity of the combination of chemotherapeutics with different targeted drugs inhibiting different pathways.

The results of the ongoing trials are keenly awaited to definitely identify the most effective strategy in BTC. Colorectal cancer is the second leading cause of death related to cancer in North America and Europe. Historically, 5-Xuorouracil (5-FU) with leucovorin was the only systemic treatment option for metastatic colorectal cancer (mCRC). More recently, there have been signiWcant advances with the introduction of several new active agents including irinotecan, oxaliplatin, bevacizumab, and cetuximab/panitumumab. In addition, the oral pro-drug of 5-FU, capecitabine, has been demonstrated to be at least equally  Vinflunine eYcacious as 5-FU as a single agent and is also associated with less myelosuppression and mucositis. Furthermore, capecitabine is more convenient as an extended intravenous infusion is not required and has been suggested to be potentially more cost eVective.

The combination of capecitabine and irinotecan (XELIRI) has been extensively evaluated. There is no evidence of pharmacokinetic interactions between these two agents and in initial studies the combination appeared to be well tolerated. Several phase II studies have been conducted to evaluate XELIRI as Wrst-line therapy for mCRC. In these studies, response rates ranged from 35 to 49%, similar to response rates seen with infusional 5-FU or bolus 5-FU and irinotecan in phase III trials. The most frequently observed severe toxicities were diarrhea and neutropenia. However, two subsequent randomized phase III trials raised concern about the potential toxicity of the capecitabine and irinotecan magazine combinations with high rates of severe diarrhea and neutropenia, and several treatment-related deaths. It is not clear if the toxicity noted was related to the dose of capecitabine and/or irinotecan in these studies, but it is possible that dose reductions in one or both agents may result in reduced toxicity and still maintain eYcacy for this combination.

In 2004, Hurwitz and colleagues demonstrated that the addition of bevacizumab to standard chemotherapy as Wrstline therapy for mCRC resulted in a signiWcant survival advantage compared with chemotherapy alone. In this study, progressive-free survival and overall survival were signiWcantly improved with the addition of bevacizumab to irinotecan and bolus 5-FU chemotherapy. To evaluate the safety and eYcacy of dose-reduced capecitabine and irinotecan given in combination with bevacizumab, we conducted a phase II study of this regime in patients with previously untreated metastatic or unresectable recurrent colorectal cancer. Exclusion criteria included concurrent other malignancies and any serious .