Adjuvant treatment in biliary tract cancer
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ABSTRACT:
SUBMITTER: Palloni A
PROVIDER: S-EPMC8798763 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Biliary tract cancer is a rare malignant tumor. There is limited knowledge about biology and natural history of this disease and considerable uncertainty remains regarding its optimal diagnostic and therapeutic management. The role of adjuvant therapy is object of debate and controversy. Although resection is identified as the most effective and the only potentially curative treatment, there is no consensus on the impact of adjuvant chemotherapy and/or radiotherapy on the high incidence of disease recurrence and on survival. This is mainly due to the rarity of this disease and the consequent difficulty in performing randomized trials. The only two prospectively controlled trials concluded that adjuvant chemotherapy did not improve survival. Most of the retrospective trials, which had limited sample size and included heterogeneous patients population and non-standardized therapies, suggested a marginal benefit of chemoradiotherapy in reducing locoregional recurrence and an uncertain impact on survival. Well-designed multi-institutional randomized trials are necessary to clarify the role of adjuvant therapy. Two ongoing phase III trials may provide relevant information.
| S-EPMC3369994 | biostudies-literature
Project description:Biliary tract cancers (BTCs) include cholangiocarcinomas and gallbladder cancers usually present at an advanced stage, which are considered resectable in less than 20% of cases and characterised by poor prognosis. In this review, we discussed the most recent therapeutic options on the basis of the most updated and complete reviews and recent prospective studies in selected BTC patients. Due to the high recurrence rate of BTCs, we suggest the new recommendations that have been made on adjuvant chemotherapy and radiotherapy treatment after surgery. New chemotherapy combinations in advanced-stage patients allow a better survival benefit than the standard treatment. Furthermore, the revelation of complex molecular events and their interactions and relationships with some risk factors allowed the development of targeted/toxic agents alone or combination with chemotherapy that is really promising. In unresectable patients, hepatic arterial infusion of high-dose chemotherapy or selective internal radiotherapy could offer a primary mass volume reduction or its resection with the maintenance of liver function. The therapeutic landscape for BTCs is blooming again, the knowledge of their biology is still growing, but the available data on chemotherapy, radiotherapy, locoregional treatments, and target therapies have added hopes to improve patient survival.
| S-EPMC7281170 | biostudies-literature
Project description:Biliary tract cancer (BTC) is a dismal disease, even after curative intent surgery. We conducted this prospective, non-randomized phase II study to evaluate the feasibility and efficacy of cisplatin and gemcitabine as adjuvant treatment in patients with resected BTC.Patients initially received gemcitabine 1000 mg/m2 alone on days 1, 8 and 15 every 28-days for a total of six cycles (single agent cohort), and after protocol amendment a combination therapy with gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 on days 1 and 8 was administered every 21 days for a total of eight cycles (combined regimen cohort). Treatment was planned to start within eight weeks after curative intent resection. Adverse events, disease-free survival and overall survival were assessed.Overall 30 patients were enrolled in the study from August 2008 and last patient was enrolled at 2nd December 2014. The follow-up of the patients ended at 31st December 2016. The first 9 patients received single-agent gemcitabine. The interim analysis met the predefined feasibility criteria and, from September 2010 on, the second group of 21 patients received the combination of cisplatin plus gemcitabine. In the single-agent cohort with gemcitabine the median relative dose intensity (RDI) was 100% (IQR 88.3-100). Patients treated with the combination cisplatin-gemcitabine received an overall median RDI of 100% (IQR 50-100) for cisplatin and 100% (IQR 75-100) for gemcitabine respectively. The most significant non-hematological adverse events (grade 3 or 4) were fatigue (20%), infections during neutropenia (10%), and two cases of biliary sepsis (7%). Abnormal liver function was seen in 10% of the patients. One patient died due to infectious complications during treatment with cisplatin and gemcitabine. The median disease-free survival (DFS) was 14.9 months (95% CI 0-33.8) with a corresponding 3-year DFS of 43.1?±?9.1%. The median overall survival (OS) was 40.6 months (95% CI 18.8-62.3) with a 3-year OS of 55.7?±?9.2%. No statistically significant differences in survival were seen between the two treatment cohorts.Adjuvant chemotherapy with gemcitabine with or without cisplatin was well tolerated and resulted in promising survival of the patients.The study was retrospectively registered on 25th June 2009 at clinicaltrials.gov ( NCT01073839 ).
| S-EPMC5765636 | biostudies-literature
Project description:Biliary tract cancer (BTC) patients who have undergone surgical resection with major hepatectomy cannot tolerate the standard gemcitabine regimen (1,000 mg/m2 on days 1, 8, and 15 every 4 weeks) due to severe toxicities such as myelosuppression. Our dose-finding study of adjuvant gemcitabine therapy for biliary tract cancer following major hepatectomy determined that the recommended dose is 1,000 mg/m2 on days 1 and 15 every 4 weeks. Here, we evaluate the pharmacokinetics and pharmacodynamics of gemcitabine in these subjects.We evaluated BTC patients scheduled to undergo surgical resection with major hepatectomy followed by gemcitabine therapy. A pharmacokinetic evaluation of gemcitabine and its main metabolite, 2',2'-difluorodeoxyuridine (dFdU), was conducted at the initial administration of gemcitabine, which was given by intravenous infusion over 30 min at a dose of 800-1,000 mg/m2. Physical examination and adverse events were monitored for 12 weeks.Thirteen patients were enrolled from August 2011 to January 2013, with 12 ultimately completing the pharmacokinetic study. Eight patients had hilar cholangiocarcinoma, three had intrahepatic cholangiocarcinoma, and one had superficial spreading type cholangiocarcinoma. The median interval from surgery to first administration of gemcitabine was 65.5 days (range, 43-83 days). We observed the following toxicities: neutropenia (n = 11, 91.7%), leukopenia (n = 10, 83.3%), thrombocytopenia (n = 6, 50.0%), and infection (n = 5, 41.7%). Grade 3 or 4 neutropenia was observed in 25% (n = 3) of patients. There were differences in clearance of gemcitabine and dFdU between our subjects and the subjects who had not undergone hepatectomy.Major hepatectomy did not affect the pharmacokinetics of gemcitabine or dFdU.UMIN-CTR in (JPRN) UMIN000005109.
| S-EPMC4669083 | biostudies-literature
Project description:Chemotherapy is indispensable for the treatment of advanced biliary tract cancer. Recently, reports regarding first-line chemotherapy have increased, and first-line chemotherapy treatment has become gradually more sophisticated. Gemcitabine and cisplatin combination therapy (or gemcitabine and oxaliplatin combination therapy) have become the standard of care for advanced biliary tract cancer. Oral fluoropyrimidines have also been shown to have good antitumor effects. Gemcitabine, platinum compounds, and oral fluoropyrimidines are now considered key drugs for the treatment of advanced biliary tract cancer. Several clinical trials using molecular targeted agents are also ongoing. Combination therapy using cytotoxic agents and molecular-targeted agents has been evaluated widely. However, reports regarding second-line chemotherapy remain limited, and it has not yet been clarified whether second-line chemotherapy can improve the prognosis of advanced biliary tract cancer. Thus, there is an urgent need to establish second-line standard chemotherapy treatment for advanced biliary tract cancer. Several problems exist when assessing the results of previous reports concerning advanced biliary tract cancer. In the present review, the current status of the treatment of advanced biliary tract cancer is summarized, and several associated problems are indicated. These problems should be solved to achieve more sophisticated treatment of advanced biliary tract cancer.
| S-EPMC3759755 | biostudies-literature
Project description:IntroductionBiliary tract cancers (BTCs) are a rare and heterogenous group with an increasing incidence and high mortality rate. The estimated new cases and deaths of BTC worldwide are increasing, but the incidence and mortality rates in South East Asia are the highest worldwide, representing a real public health problem in these regions. BTC has a poor prognosis with a median overall survival <12 months. Thus, an urgent unmet clinical need for BTC patients exists and must be addressed.ResultsThe backbone treatment of these malignancies is chemotherapy in first- and second-line setting, but in the last decade a rich molecular landscape has been discovered, expanding conceivable treatment options. Some druggable molecular aberrations can be treated with new targeted therapies and have already demonstrated efficacy in patients with BTC, improving clinical outcomes, such as the FGFR2 or IDH1 inhibitors. Many other molecular alterations are being discovered and the treatment of BTC will change in the near future from our current clinical practice.ConclusionsIn this review we discuss the epidemiology, molecular characteristics, present treatment approaches, review the recent therapeutic advances, and explore future directions for patients with BTC. Due to the rich molecular landscape of BTC, molecular profiling should be carried out early. Ongoing research will bring new targeted treatments and immunotherapy in the near future.
| S-EPMC9198382 | biostudies-literature
Project description:BackgroundRecent studies have reported TIMs play an important role in tumors progression or regression, but the effect of TIMs in biliary tract cancer remains unclear. The aim of this study is to investigate the prognostic value of tumor infiltrating mast cells (TIMs) and its influence on gemcitabine-based adjuvant chemotherapy (ACT) benefits in biliary tract cancer patients after surgery.MethodsTIMs were evaluated by immunohistochemical staining of tryptase in 250 patients with resected gallbladder carcinoma (GBC) or extrahepatic bile duct carcinoma (EBDC) from Zhongshan Hospital. The relationships between TIMs and clinicopathological factors and postoperative prognosis were analyzed respectively.ResultsHigh TIMs infiltration was significantly correlated with prolonged overall survival (OS). Furthermore, multivariate analysis indicated TNM stage and TIMs as independent prognostic factors for OS. Patients with high TIMs infiltration appeared to significantly benefit from Gemcitabine-based ACT in the discovery and validation cohorts. Spearman analysis identified that TIMs infiltration were positively correlated with anti-tumor CD8+ T cells.ConclusionTIMs infiltration is an independent favorable prognostic factor in GBC and EBDC patients, which could better stratify patients with different prognosis and predict benefit from gemcitabine-based ACT.
| S-EPMC5863450 | biostudies-literature
Project description:Management of biliary tract cancers (BTCs) is rapidly evolving. Curative management relies on surgical resection followed by adjuvant capecitabine for cholangiocarcinoma and gallbladder cancers. Unfortunately relapse rate remains high, and better adjuvant strategies are urgently required. A majority of patients are diagnosed with advanced disease, when chemotherapy with cisplatin and gemcitabine followed by second-line 5-FU and oxaliplatin /irinotecan is the cornerstone of treatment for most patients in the absence of targetable alterations. Targeted therapies, including therapies for tumours with fibroblast growth factor receptor-2 (FGFR-2) fusions, isocitrate dehydrogenase-1 (IDH-1) mutations, B-Raf proto-oncogene serine/threonine kinase (BRAF) V600E mutations, neurotrophic tyrosine receptor kinase (NTRK) fusions, Human epidermal growth factor-2 (HER-2) amplifications, and/or microsatellite instability are rapidly changing the treatment paradigm for many patients with advanced BTC, especially for patients with intrahepatic cholangiocarcinoma. Because of this, molecular profiling should be considered early on patients pathway to allow adequate planning of therapy. Ongoing research is likely to clarify the role of immunotherapy, liver-directed therapy, and liver transplant for BTCs in the future.
| S-EPMC8762076 | biostudies-literature
Project description:Biliary tract cancers (BTC) is a group of malignancies that arise from the epithelial cells of the biliary tree. These cancers are typically classified by anatomic site of origin: intrahepatic cholangiocarcinoma (IHCC) and extrahepatic cholangiocarcinoma (EHCC), and gallbladder cancer (GBC). To date, complete surgical resection remains the mainstay of treatment especially for earlier stage disease. Unfortunately, most patients present with advanced or metastatic disease, when systemic chemotherapy is the only treatment option. Due to the paucity of effective treatments, BTCs have a dismal prognosis. There is a tremendous need to better understand the disease biology, discover new therapies, and improve clinical outcomes for this challenging disease. Next-generation sequencing has produced a more accurate and detailed picture of the molecular signatures in BTCs. The three BTC histologic subtypes are, in fact, quite molecularly distinct. IHCC commonly contain FGFR2 fusions and IDH 1 and 2 mutations, whereas EHCC and GBC tend to carry mutations in EGFR, HER2, and MAPK pathway. In light of this emerging knowledge, clinical trials have become more biomarker-driven, which allows capturing of subsets of patients that are most likely to respond to certain therapies. Many new and promising targeted therapeutics are currently in the pipeline. Here we review the genetic landscape of BTCs while focusing on new molecular targets and targeted therapeutics currently being investigated in biomarker-driven clinical trials.
| S-EPMC5506280 | biostudies-literature
Project description:Advanced biliary tract cancers (BTC) include a diverse collection of rare and heterogenous tumors with poor prognosis. The combination of gemcitabine and cisplatin is the established first-line therapy for advanced BTC. There are no accepted standard treatments in the second line setting, though there are several ongoing clinical trials that implement chemotherapy as a therapeutic strategy. The understanding of the molecular landscape of BTC has offered hope of targeted therapies to the identified actionable genomic aberrations, such as FGFR2 gene fusions, mutations of IDH1/2, HER2, BRAC1/2 and BRAF. Pembigatinib has become the first approved targeted therapy for BTC with FGFR2 fusion or other rearrangements. Recent immunotherapy has opened new therapy avenues in BTC with pembrolizumab approved for either microsatellite instability high (MSI-H) or DNA mismatch repair deficient (dMMR) advanced solid tumors, including BTC. The combination of immunotherapy with other modalities is currently being evaluated in different clinical trials, since single agent immunotherapy appears to provide modest benefits in advanced BTC. In this review, we summarize the current status of treatment options, including systemic chemotherapy, targeted therapy, immunotherapy, and various combinations in advanced BTC.
| S-EPMC7519922 | biostudies-literature