PHY906, a Chinese medicinal formula consisting of 4 different herbs, has been in use for some 1800 years to treat gastrointestinal (GI) ailments including diarrhea, nausea and vomiting. These side effects are quite common in patients undergoing cancer chemotherapy, thereby raising the possibility of using PHY906 to alleviate such symptoms in cancer patients and improve their quality-of-life. In a tumor-bearing mouse model, PHY906 significantly decreased host toxicity induced by CPT-11-based chemotherapy by reducing mortality and loss in body weight. Of note, PHY906 enhanced the antitumor activity of various chemotherapeutic agents including CPT-11, CPT-11/5-FU/LV, and capecitabine in both colorectal and liver tumor mouse models. PHY906 did not significantly change the pharmacokinetics or tissue distribution of CPT-11-, CPT-11/5-FU/LV-, or capecitabine-based treatments. The mechanism of action of PHY906 is multi-factorial, including modulation of various cytokines, enhancing cell permeability and transport of active chemical(s), and regulating NF-kB expression. A comprehensive panel of chemical and biological fingerprints has been developed to ensure product consistency of PHY906. This herbal preparation is currently being studied as a potential cytoprotective agent in a phase I/IIa clinical trial in colorectal cancer patients treated with CPT-11/5-FU/LV (Saltz regimen) in first line or CPT-11 alone in second line treatment of patients with advanced colorectal cancer. A second clinical trial is being designed to determine whether PHY906 enhances the antitumor activity of capecitabine in patients with hepatocellular cancer. |