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Abstract
Despite advances in our understanding of the molecular and genetic basis of pancreatic cancer, it continues to be a therapeutic challenge. Gemcitabine approved by FDA in 1997, offers modest improvement of tumor-related symptoms and marginal advantage of survival. Many chemotherapeutic agents have been compared against or combined with gemcitabine in randomized Phase III trials and no drug was shown to be superior to single-agent gemcitabine except FOLFIRINOX and nab-paclitaxel plus gemcitabine. On the other hand, efforts to integrate targeted agents such as BAY 12-9566, SCH 66336, bevacizumab, cetuximab, axitinib and sorafenib have been quite dismal despite extensive pre-clinical and clinical research over the last decade in the field of novel agents. To date, erlotinib remains the only biological agent that has demonstrated a small, but significant, added benefit to single agent gemcitabine. However, numerous new agents, including monoclonal antibodies and tyrosine kinase inhibitors, are currently being tested in an attempt to achieve better response, while maintaining a safe toxicity profile. In this article, the author discusses the management of advanced pancreatic and the current role of novel agents in this setting.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.
No writing assistance was utilized in the production of this manuscript.
Key issues
Pancreatic cancer is responsible for 6% of all cancer-related mortality, retaining its position as the fourth cause of cancer-related death.
Gemcitabine, approved by the US FDA in 1997, offers modest improvement of tumor-related symptoms and marginal advantage of survival.
Two large randomized Phase III studies in pancreatic cancer have demonstrated the superiority of a gemcitabine-containing combination over single-agent gemcitabine: erlotinib + gemcitabine versus gemcitabine and nab-paclitaxel + gemcitabine versus gemcitabine.
Although the survival improvement with erlotinib + gemcitabine was statistically significant, the clinical relevance was evidently questionable whether the 2-week improvement in survival is clinically meaningful.
Nab-paclitaxel + gemcitabine now offers a new option for first-line treatment of advanced pancreatic cancer.
5-fluorouracil leucovorin, oxaliplatin and irinotecan also offer a treatment option for patients with advanced pancreatic cancer who have a good performance status.
The targeted agents, including bevacizumab, cetuximab and erlotinib have been dismal.
Numerous novel therapeutic avenues targeting tumor cells, tumor vasculature and stroma are currently under evaluation in clinical trials.
Molecular markers are urgently needed that are able to predict therapeutic responsiveness or resistance to a given drug in an approach toward a personalized medicine.