Synergistic Effect Between Juzen-taiho-to, a Japanese Traditional Herbal Medicine, and Gemcitabine Single-Agent Chemotherapy for Advanced Biliary Tract Cancer

Abstract

This is the first report of the successful treatment of advanced biliary tract cancer with gemcitabine single-agent chemotherapy in combination with Juzen-taiho-to (JTT), a Japanese traditional herbal medicine. An 84-year-old woman was referred to our hospital with general fatigue and appetite loss; she was diagnosed with advanced biliary tract cancer and accompanying colonic invasion and hepatic metastasis. The patient's response to combination chemotherapy was extremely good, and her tumors disappeared. Recent studies have confirmed the occurrence of spontaneous and induced antitumor immune responses, carried out by tumor-infiltrating lymphocytes in the tumor microenvironment. The availability, antigen presentation, and proliferation of these immune cells are increased by cytokines such as granulocyte macrophage colony-stimulating factor (GM-CSF) and interleukin (IL)-2. Recently, JTT has gained recognition as a biological response modifier that has stimulatory effects on systemic immune responses such as enhancement of cytokine expression (GM-CSF, IL-2, etc.). In addition, some chemotherapy agents, such as anthracyclines and gemcitabine, are effective boosters of the immune response through tumor-specific antigen overexpression after apoptotic tumor cell destruction. These findings suggest that JTT enhances the antitumor effects of gemcitabine, in particular its tumor-specific effects on immune response, and these drugs are a good combination for advanced biliary tract cancer therapy.

Japanese Kampo Medicine Juzentaihoto Enhances Antitumor Immunity in CD1d−/− Mice Lacking NKT Cells

“…40 Furthermore, a study on advanced biliary tract cancer has shown that the tumor was successfully treated by combining GEM single-agent chemotherapy with JTT. 41 A marginal impact on overall survival of advanced pancreatic cancer patients was observed following treatment with JTT combined with GEP (GEM + 5-fluorouracil + cisplatin) therapy. 42 While MDSC's role was not described in these 2 studies, their observations suggest that using a combinatorial cancer immunotherapy (ie, JTT and GEM) may represent a strategy for a more effective MDSC targeting.…”

Sipjeondaebo-tang in patients with breast cancer with fatigue: a protocol for a pilot, randomised, double-blind, placebo-controlled, cross-over trial

“… 35 A case report suggested that SJDBT combined with gemcitabine enhances the antitumour effects in advanced biliary tract cancer. 36 Furthermore, SJDBT protects against carbon tetrachloride-induced anorexia and hepatotoxicity, 37 protects the gastric mucosa by exerting antioxidant effects, 38 inhibits retinal neovascularisation by inhibiting angiogenesis 39 and restraint stress. 40 Its potential therapeutic effect on Alzheimer’s disease has also been reported.…”

Recent Advances in Herbal Medicines for Digestive System Malignancies

“…Recently, some studies revealed TJ-48 might play a role in immune regulation and tumor treatment (Ikemoto et al, 2014 ). This medication can alleviate side effects caused by chemotherapy and radiotherapy during the treatment of DSM, and also prevent metastasis (Nishiuchi et al, 2013 ; Amitani et al, 2015 ). Ikemoto discovered TJ-48 could increase activity of T cells, based on decreased Foxp3 + Tregs in patients with advanced pancreatic cancer (Ikemoto et al, 2014 ).…”

“…Ikemoto discovered TJ-48 could increase activity of T cells, based on decreased Foxp3 + Tregs in patients with advanced pancreatic cancer (Ikemoto et al, 2014 ). Another study indicated that TJ-48 might slow liver cancer progression and lengthen recurrence-free survival by suppressing Kupffer cell-mediated oxidative stress (Nishiuchi et al, 2013 ).…”