Pancreatic Cancer (PDAC): Introduction of Evidence-Based Complementary Measures into Integrative Clinical Management

SIMPLE SUMMARY: Pancreatic ductal adenocarcinoma is a devastating disease that is very hard to treat. Here, we advance and evaluate the notion that the best possible management currently would be possible by combining clinical procedures with evidence-based complementary measures. We evaluate three categories of such complementary measures: Diet (background and specific), nutraceutical agents and lifestyle factors. Altogether, these include alkalinity, low-glycemic index, low-cholesterol, red meat, fish, fruit/vegetables, dairy, honey, coffee, vitamins A, C, D, E, genistein and curcumin (dietary issues); propolis, triptolide and cannabidiol (nutraceuticals); and obesity, diabetes, smoking, alcohol and exercise (lifestyle factors). The available evidence is considered by four criteria: clinical trials, meta-analyses and in vivo and in vitro data. A total of nine agents satisfy these criteria. These are combined and divided into two groups. Finally, a scheme is proposed for integrating the two groups with gemcitabine chemotherapy on a weekly cycle. ABSTRACT: The most common form of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC), which comprises some 85% of all cases. Currently, this is the fourth highest cause of cancer mortality worldwide and its incidence is rising steeply. Commonly applied clinical therapies offer limited chance of a lasting cure and the five-year survival rate is one of the lowest of the commonly occurring cancers. This review cultivates the hypothesis that the best management of PDAC would be possible by integrating ‘western’ clinical medicine with evidence-based complementary measures. Protecting the liver, where PDAC frequently first spreads, is also given some consideration. Overall, the complementary measures are divided into three groups: dietary factors, nutraceutical agents and lifestyle. In turn, dietary factors are considered as general conditioners, multi-factorial foodstuffs and specific compounds. The general conditioners are alkalinity, low-glycemic index and low-cholesterol. The multi-factorial foodstuffs comprise red meat, fish, fruit/vegetables, dairy, honey and coffee. The available evidence for the beneficial effects of the specific dietary and nutraceutical agents was considered at four levels (in order of prominence): clinical trials, meta-analyses, in vivo tests and in vitro studies. Thus, 9 specific agents were identified (6 dietary and 3 nutraceutical) as acceptable for integration with gemcitabine chemotherapy, the first-line treatment for pancreatic cancer. The specific dietary agents were the following: Vitamins A, C, D and E, genistein and curcumin. As nutraceutical compounds, propolis, triptolide and cannabidiol were accepted. The 9 complementary agents were sub-grouped into two with reference to the main ‘hallmarks of cancer’. Lifestyle factors covered obesity, diabetes, smoking, alcohol and exercise. An integrative treatment regimen was devised for the management of PDAC patients. This involved combining first-line gemcitabine chemotherapy with the two sub-groups of complementary agents alternately in weekly cycles. The review concludes that integrated management currently offers the best patient outcome. Opportunities to be investigated in the future include emerging modalities, precision medicine, the nerve input to tumors and, importantly, clinical trials.