Chemotherapy and Targeted Therapy in Advanced Biliary Tract Carcinoma: A Pooled Analysis of Clinical Trials

Eckel, Florian; Schmid, Roland M.

doi:10.1159/000365781

Cited by 44 publications

(30 citation statements)

References 25 publications

(31 reference statements)

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“…Advanced or unresectable locally advanced disease has a poor prognosis with limited systemic treatment options. 1 Combination platinum-gemcitabine chemotherapy is an active first-line treatment regimen; 2 however, it is associated with low rates of radiologic response and short time to tumour progression. Effective new treatments are therefore urgently required.…”

Section: Introductionmentioning

confidence: 99%

Phase II study of everolimus (RAD001) monotherapy as first-line treatment in advanced biliary tract cancer with biomarker exploration: the RADiChol Study

et al. 2018

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Section: Introductionmentioning

confidence: 99%

Phase II study of everolimus (RAD001) monotherapy as first-line treatment in advanced biliary tract cancer with biomarker exploration: the RADiChol Study

et al. 2018

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“…In 2007, a pooled analysis of 104 clinical trials, including 2810 treated patients, showed better response rate (RR, 28% vs 15.3%, P = 0.000), disease control rate (DCR, 61% vs 50.4%, P = 0.000), time to progression (4.4 vs 3.4 months, P = 0.015) and a trend for improved OS (median 9.3 vs 7.5 months, P = 0.061) for doublet chemotherapy compared with monotherapy. 19 Interestingly, the same study suggested gemcitabine combined with cisplatin or oxaliplatin as the most active regimen based on increased RR and DCR as compared with other combinations.…”

Section: First-line Chemotherapymentioning

confidence: 99%

Medical treatment for cholangiocarcinoma

Adeva

Sangro

Salati

et al. 2019

Liver International

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Most of the patients with cholangiocarcinoma (CCA) present with advanced (inoperable or metastatic) disease, and relapse rates are high in those undergoing potentially curative resection. Previous treatment nihilism of patients with advanced disease has been replaced by active clinical research with the advent of randomized clinical trials (RCTs) and a much greater effort at understanding molecular mechanisms underpinning CCA. Three RCTs have recently been reported evaluating adjuvant chemotherapy following curative resection; only one of these has the potential to change practice. The BILCAP study failed to meet its primary endpoint by intention‐to‐treat analysis; however, a survival benefit was seen in a preplanned sensitivity analysis (predominantly adjusting for lymph nodes status). This, along with the numerical difference in median overall survival has led to the uptake of adjuvant capecitabine by many clinicians. In patients with advanced disease, the only level 1 data available supports the use of cisplatin and gemcitabine for the first‐line treatment of patients with advanced disease; there is no established second‐line chemotherapy. Previous forays into targeted therapy have proven unfruitful (namely targeting the epithelial growth factor receptor and vascular endothelial growth factor pathways). An increasing number of genomic subtypes are being defined; for some of these on‐target therapeutic options are under active investigation. The most developed are studies targeting IDH‐1 (isocitrate dehydrogenase) mutations and FGFR‐2 (fibroblast growth factor receptor) fusions, with promising early results. Several other pathways are under evaluation, along with early studies targeting the immune environment; these are too premature to change practice to date. These emerging treatments are discussed.

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“…Addition of fluoropyrimidine or gemcitabine based chemotherapy plus targeted therapy mainly against epidermal growth factor receptor yielded even better outcomes compared to gemcitabine platinum alone. 132 …”

Section: Chemotherapy For Unresectable or Metastatic Diseasementioning

confidence: 99%

Comprehensive management of cholangiocarcinoma: Part II. Treatment

Papafragkakis

Lee

2017

Int J Gastrointest Interv

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Cholangioarcinoma is a rare but dreadful malignancy which poses much difficulties in the management. If detected early with only localized disease, curative resection is possible. However, most patients present in the late stages of the disease, which are managed with endoscopic biliary drainage and/or chemoradiation. Liver transplantation offers a possibility for cure in the distal and the perihilar tumors for selected candidates. Local treatments, such as hepatic artery-based therapies, brachytherapy, and photodynamic therapy, may offer some benefit in cases of the advanced disease. In this review, we will assess the role of preoperative biliary drainage, how best to drain biliary obstruction, and the intricate details of various treatments that are currently available. Management of Cholangiocarcinoma Preoperative biliary drainagePreoperative biliary drainage (PBD) is achieved with endoscopic or percutaneous approach. The topic is controversial and the review of the literature revealed conflicting results. PBD of the future remnant hepatic lobe is supposed to decrease hepatic dysfunction and liver failure postoperatively.1 The meta-analysis found no difference in mortality between patients with and without PBD and the authors advised that such procedure should not be performed routinely.2 Another meta-analysis of almost 5,000 patients with distal obstruction (425 with distal cholangiocarcinoma [DCC]) did not find any evidence that PBD (without distinguishing between endoscopic or percutaneous approach) increases morbidity or mortality. However it was associated with significant bacterial infection of the bile and possibly adverse outcomes after surgery.3 Other studies showed that PBD reduced jaundice, which positively affected outcomes, but not survival, and that it might be associated with more intraoperative blood loss, but less reoperation rates compared to non-drained cases. 4,5 The prospective randomized study of almost 200 patients with cancer of the head of the pancreas demonstrated that PBD was associated with more non-surgical adverse events compared to those managed only with surgery (46% vs 2%, respectively). Surgical adverse events were also more in the PBD group (47% vs 37%). The high incidence of cholangitis in those treated with PBD may be associated with the long lag time between PBD and surgery (5 weeks) and the high occlusion rate of plastic stents (PSs) (15%), prompting other authors to suggest that use of short, self-expandable metal stents (SEMS) may result in better outcomes for distal bile duct strictures. In accordance with other studies, there was no effect of PBD on mortality.6,7 In perihilar cholangiocarcinoma (PCC), the systematic review of 700 patients with and without PBD suggested that there is higher incidence of postoperative infections (18%-52% vs 0%-27%) and overall adverse events (36%-100% vs 29%-72%) in the PBD compared to the non-PBD group. There was no difference in mortality in the two groups. 8 Other studies favor the use of PBD in the preoperative management of PCC. ...

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Chemotherapy and Targeted Therapy in Advanced Biliary Tract Carcinoma: A Pooled Analysis of Clinical Trials

Cited by 44 publications

References 25 publications

Phase II study of everolimus (RAD001) monotherapy as first-line treatment in advanced biliary tract cancer with biomarker exploration: the RADiChol Study

Phase II study of everolimus (RAD001) monotherapy as first-line treatment in advanced biliary tract cancer with biomarker exploration: the RADiChol Study

Medical treatment for cholangiocarcinoma

Comprehensive management of cholangiocarcinoma: Part II. Treatment

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