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.
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. The standard first-line treatment for PDAC is gemcitabine chemotherapy which, unfortunately, offers only limited chance of a lasting cure. This review further evaluates the hypothesis that the effectiveness of gemcitabine can be improved by combining it with evidence-based complementary measures. Previously, supported by clinical trial data, we suggested that a number of dietary factors and nutraceuticals can be integrated with gemcitabine therapy. Here, we evaluate a further 10 agents for which no clinical trials have (yet) been carried out but there are promising data from in vivo and/or in vitro studies including experiments involving combined treatments with gemcitabine. Two groups of complementary agents are considered: Dietary factors (resveratrol, epigallocatechin gallate, vitamin B9, capsaicin, quercetin and sulforaphane) and nutraceutical agents (artemisinin, garcinol, thymoquinone and emodin). in addition, we identified seven promising agents for which there is currently only basic (mostly in vitro) data. Finally, as a special case of combination therapy, we highlighted synergistic drug combinations involving gemcitabine with "repurposed" aspirin or metformin. we conclude overall that integrated management of PDAC currently is likely to produce the best outcome for patients and for this a wide range of complementary measures is available.
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