PHY906 is a traditional Chinese botanical formulation comprised of four different herbs, and it has been used for over 1800 years to treat gastrointestinal ailments, some of which are commonly observed side-effects in cancer patients undergoing chemotherapy. We found that PHY906 reduced chemotherapy-induced toxicities, including body weight loss and mortality, in addition to enhancing the antitumor efficacy of a broad-spectrum of anticancer agents, such as CPT-11, 5-FU, CPT-11/5-FU/LV, VP-16, and L-OddC in mouse colorectal cancer models.

PHY906 has also been co-administrated with either the oral 5-FU prodrug capecitabine or CPT-11 in human hepatocellular xenografts mouse models and with gemcitabine in mouse pancreatic cancer models. The studies show that PHY906 significantly enhanced the therapeutic index of the chemotherapeutic agents.  The studies also revealed that co-administration of PHY906 and capecitabine and PHY906 and gemcitabine in animal models did not alter the pharmacokinetic profile of capecitabine, gemcitabine, or their respective metabolites. 

Our biochemical studies revealed that the PHY906 formulation possesses a wide range of pharmacological activities.  The potential mechanism(s) of action of PHY906 include (1) enhancement of cellular uptake of chemotherapeutic agents via inhibition of MDR; (2) inhibition of NF-kB activity; (3) inhibition of MMP activity; and (4) inhibition of angiogenesis.

These preclinical in vivo studies have provided rationale for developing PHY906 in the clinical setting. Currently a phase I/II open-label dose escalation clinical trial has been opened to patient enrollment to evaluate the role of PHY906 in combination with capecitabine in the treatment of hepatocellular carcinoma.