New directions in the management of advanced pancreatic cancer: a review

Abstract

Complete surgical resection is the only potentially curative option for pancreatic cancer. However, most patients have advanced/metastatic disease at the time of diagnosis, or will relapse after surgery. Systemic chemotherapy is only palliative. Gemcitabine-based therapy is an acceptable standard for unresectable locally advanced/metastatic pancreatic cancer, but average median survival is only 6 months. The addition of other chemotherapies (including other antimetabolites, platinum, and topoisomerase I inhibitors) or targeted therapies (farnesyl transferase inhibitors, metalloproteinase inhibitors, cetuximab and bevacizumab) to gemcitabine has failed to improve outcome. The combination of gemcitabine and erlotinib, a small-molecule tyrosine kinase inhibitor of the human epidermal growth factor receptor, was recently approved by the US/European authorities for use in advanced disease. In a phase III trial, the combination demonstrated a significant improvement in overall survival compared with gemcitabine monotherapy. Positive efficacy results have also been observed in a phase III trial, favoring the addition of capecitabine to gemcitabine compared with gemcitabine alone. This review focuses on the recent developments in systemic treatment, and discusses how novel agents might be incorporated into future treatment strategies for pancreatic cancer.

Diagnóstico, estadiamento e tratamento cirúrgico do adenocarcinoma de pâncreas

“…Quando analisado a totalidade dos pacientes, apenas em 15-20% dos casos a ressecção é possível em virtude de doença avançada localmente ou pela presença de metástase à distância. Nesses casos é esperada sobrevida média de aproximadamente seis meses 33 .…”

“…Quando analisado a totalidade dos pacientes, apenas em 15-20% dos casos a ressecção é possível em virtude de doença avançada localmente ou pela presença de metástase à distância. Nesses casos é esperada sobrevida média de aproximadamente seis meses 33 .Em virtude dessa realidade, o cirurgião tem papel central na abordagem do AP sendo seus objetivos: 1) promover a ressecção cirúrgica com margens livres e 2) proporcionar um mínimo possível de morbidade e mortalidade com o tratamento. Acrescenta-se a isso a participação no processo decisório quanto à melhor paliação possível a ser aplicada aos pacientes que pode ser realizada de forma cirúrgica ou endoscópica.…”

Changing Pathology with Changing Drugs: Tumors of the Gastrointestinal Tract

“…In a phase III trial, this combination demonstrated a significant improvement in overall survival compared with gemcitabine monotherapy [84] . In the future, treatment of pancreatic cancer may be influenced by the potential of certain biomarkers to predict better responses to molecular targeted therapies, allowing the individualization of patient therapy [85,86] .…”

Inhibition of cysteine peptidase activity in ascitic fluid in pancreatic cancer patients.

“…However, they do not seem to have satisfactory treatment effectiveness. For some time now synthetic tissue metaloproteinase inhibitors (TIMPs) have been utilised in intravenous and intraperitoneal treatment; these are used by tumour cells to destroy and remodel tissue stroma as part of metastasis, but they also block angiogenesis, stopping local infiltration, and enable tumor encapsulation [8,9].…”

“…Intraperitoneal chemotherapy uses cytostatics that have a small molecular weight and so penetrate through the membrane separating ascitic fluid from the patient's blood, making their way into the blood and causing the same side effects as in the case of intravenous chemotherapy. Intraperitoneal treatment is used for neoplasms of the ovary, pancreas or liver [6,7].…”