review of literature on clinical pancreatology - The Pancreapedia

errors were attributable to unforeseen ambiguities in protocol documentation. They wereaddressed by feedback and corresponding amendments to protocol documentation.Summary radiobiological measures including total weighted normal tissue equivalent uniformdose varied significantly between centres. This accreditation exercise successfully identifiedsignificant potential sources <strong>of</strong> protocol violations, which were then easily corrected. It wasbelieved that this process should be applied to all clinical trials involving radiotherapy. Due tothe limitations <strong>of</strong> data analysis with hard-copy information only, it is recommended thatcomplete planning datasets from treatment-planning systems be collected through a digitalsubmission process [563].Novel agentsPancreatic cancer is a particularly challenging malignancy, given its usually advanced stageat diagnosis and its rather limited treatment options. Gemcitabine has been standard therapyfor advanced pancreatic cancer for well over a decade. The addition <strong>of</strong> capecitabine orerlotinib to gemcitabine has resulted in modestly improved, although still poor, overallsurvival. The majority <strong>of</strong> the recently completed randomized trials, however, have failed todemonstate an improvement <strong>of</strong> newer treatments over single-agent gemcitabine. Effortscurrently underway center on new cytotoxic chemotherapy drugs, as well as novel targetedagents inhibiting various molecular pathways. Newly discovered proteins and cellularelements involved in tumor growth and invasion are potential therapeutic targets, and havebecome the focus <strong>of</strong> current trials, as well as future clinical trials. A better understanding <strong>of</strong>the biology <strong>of</strong> the disease at the basic science level, and epidemiology and risk factors froma public-health perspective, are needed [564].Stem cell transplantationAdvanced unresectable pancreatic cancer has an extremely poor prognosis despite intensivechemotherapy. As a new therapeutic modality, it was investigated nonmyeloablativeallogeneic hematopoietic stem cell transplantation from a related donor. Five patients withchemotherapy-resistant pancreatic cancer received allogeneic peripheral blood stem celltransplantation after a conditioning regimen consisting <strong>of</strong> low-dose total body irradiation andfludarabine. The prophylaxis for graft-versus-host disease consisted <strong>of</strong> mycophenolatem<strong>of</strong>etil and cyclosporine. The median age <strong>of</strong> the 5 patients was 54 years, and the medianduration from diagnosis to nonmyeloablative allogeneic hematopoietic stem celltransplantation was 10 months. Three <strong>of</strong> the 5 patients achieved complete donor chimerism<strong>of</strong> peripheral T cells, at a median time <strong>of</strong> day 42. Acute graft-versus-host disease developedin 3 patients: grade 2 in 2 patients and grade 1 in 1. Tumor reduction was observed in 2patients: 1 patient showed disappearance <strong>of</strong> the pancreatic tumor, and the other patientshowed approximately 20 percent reduction <strong>of</strong> the tumor. Marked elevation <strong>of</strong> tumor necrosisfactor-alpha was observed as the tumor regressed. It was concluded that lthough advancedpancreatic cancer progresses rapidly, some graft-versus-tumor effects and pivotal role <strong>of</strong>tumor necrosis factor-alpha were suggested [565].BetulinBetulin and betulinic acid are naturally occurring pentacyclic triterpenes showing cytotoxicitytowards a number <strong>of</strong> cancer cell lines. These compounds can be found in the bark <strong>of</strong> themany plants. In one report it was compared the cytotoxic activity <strong>of</strong> crude birch bark extractand purified betulin and betulinic acid towards human gastric carcinoma (EPG85-257) andhuman pancreatic carcinoma (EPP85-181) drug-sensitive and drug-resistant (daunorubicinand mitoxantrone) cell lines. The results show significant differences in sensitivity betweencell lines depending on the compound used, and suggest that both betulin and betulinic acidcan be considered as a promising leads in the treatment <strong>of</strong> cancer [566].