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

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.

Stroma Involvement in Pancreatic Ductal Adenocarcinoma: An Overview Focusing on Extracellular Matrix Proteins

“…However, PEGPH20 in combination with conventional chemotherapies failed to demonstrate an improvement in median overall survival, leading to the recent discontinuation of PEGPH20 development after a phase 3 clinical trial. Minnelide, corresponding to an active substance extracted from thunder god vine is still under investigation and its mechanism of action seems multimodal (132,(138)(139)(140). Additionally, abnormal glycosylation of ECM components such as proteoglycans and glycoproteins can significantly influence tumor growth, neoplastic progression, metastasis and chemoresistance and thus should be considered for new drug design (141,142).…”

Development of Possible Next Line of Systemic Therapies for Gemcitabine-Resistant Biliary Tract Cancers: A Perspective from Clinical Trials

“…Recently, complementary agents for the integrated management of cancer in several malignancies had been described, such as pancreatic cancer and colon cancer [ 140 , 141 ]. The major functions of most complementary agents in cancer treatment focus on the relief of cancer cachexia and fatigue, as well as in combination with cytotoxic agents to have synergistic effect.…”

Integrative Management of Pancreatic Cancer (PDAC): Emerging Complementary Agents and Modalities

“…In our previous review we considered dietary factors in 3 different categories (16). General/background conditioners included acidity, glycaemic index and cholesterol.…”

“…Whilst our understanding of this association has come a long way over the years, we know much less about how dietary and nutraceutical agents, as well as lifestyle factors, could associate with PDAC during treatment (15). In our previous review, we advanced the hypothesis that the best outcome for PDAC currently would be obtained by integration of clinical medicine with evidence-based natural complementary agents and lifestyle factors (16). Of the former, 9 (six dietary and three nutraceutical compounds) were chosen based upon evidence from clinical trials as the essential criterion, as well as meta-analyses and in vivo and in vitro experiments.…”

“…Central to our approach, again, is the epigenetic nature of cancer, including PDAC, which means that genes and their products can be regulated significantly including by dietary and lifestyle factors (16)(17)(18)(19)(20). Indeed, overall, ca.…”