The latest clinical trials of gemcitabine in biliary tract cancer

Biliary tract cancer(BTC) is an uncommon but aggressive disease, characterized by high rates of recurrence and mortality. It is contributing to a significant disease burden and poor outcomes. Currently, surgical resection is the sole curative treatment available; unfortunately, most patients are not eligible for surgery at the time of diagnosis. Recently, advancements in chemotherapy have emerged, with gemcitabine being the primary treatment for locally advanced and metastatic cases of biliary tract cancer. However, responses to gemcitabine are generally suboptimal across patients. Methods: A literature search was conducted using PubMed, Scopus, and Web of Science databases, covering RCTs published ۲۰۱۹ to September of ۲۰۲۴. Keywords such as " Biliary tract cancer," " Gemcitabine," and " Treatment," were used. Results: The combination of gemcitabine and cisplatin shows efficacy in treating advanced BTC, with the addition of durvalumab presenting a tolerable regimen without negative impacts on patient-reported outcomes. Pembrolizumab alongside gemcitabine and cisplatin demonstrates statistically significant improvements in overall survival, suggesting it as a viable option for previously untreated metastatic or unresectable BTC. DKN-۰۱ at ۳۰۰ mg was well tolerated, although its additional efficacy remains unclear. For second-line therapies, trastuzumab biosimilars combined with FOLFOX show promising activity and acceptable toxicity in HER۲-positive cases, advocating for FOLFOX as a new standard of care post-cisplatin and gemcitabine failure. While pemetrexed plus erlotinib had limited efficacy after gemcitabine, single-agent irinotecan is preferred for previously treated gallbladder cancer patients. Varlitinib with capecitabine did not demonstrate enhanced efficacy but indicated potential benefits in female and gallbladder cancer patients. FF-۱۰۵۰۲-۰۱ showed promise with manageable side effects in heavily pretreated patients, while ramucirumab provided similar PFS outcomes as traditional chemotherapy in chemorefractory settings. Lastly, regorafenib exhibited improved PFS and tumor control in patients receiving second- or third-line treatments. Overall, these findings emphasize the need for continued exploration of various therapeutic combinations and regimens to optimize treatment for advanced biliary tract cancer. Conclusion: In conclusion, while significant advancements have been made in the treatment of advanced biliary tract cancer, the optimal management of this aggressive disease remains a challenge due to its complex nature and varied patient responses. Current therapies, particularly the combinations involving gemcitabine and cisplatin, along with newer agents like pembrolizumab and trastuzumab biosimilars, show promise in improving patient outcomes. However, the need for individualized treatment strategies is paramount, as suboptimal responses to existing regimens are still common. Future studies should focus on identifying predictive biomarkers to guide therapy selection, exploring novel drug combinations, and conducting larger, multicenter clinical trials to validate emerging treatment options. Additionally, investigating the molecular underpinnings of biliary tract cancer may unveil new therapeutic targets, ultimately improving survival rates and quality of life for affected patients. Continued research in this area is crucial to advance the standard of care and address the unmet needs in the management of this challenging malignancy.

کلیدواژه ها:

Biliary tract cancer ، Gemcitabine ، RCT