TY - JOUR
T1 - A phase I study of the chinese herbal medicine PHY906 as a modulator of irinotecan-based chemotherapy in patients with advanced colorectal cancer
AU - Kummar, Shivaani
AU - Sitki Copur, M.
AU - Rose, Michal
AU - Wadler, Scott
AU - Stephenson, Joe
AU - O'Rourke, Mark
AU - Brenckman, Wayne
AU - Tilton, Robert
AU - Liu, Shwu Huey
AU - Jiang, Zaoli
AU - Su, Tahmun
AU - Cheng, Yung Chi
AU - Chu, Edward
PY - 2011/6
Y1 - 2011/6
N2 - PHY906 is a novel Chinese herbal preparation that has been used in the Orient for over 1800 years to treat a wide range of gastrointestinal side effects including diarrhea, abdominal cramps, vomiting, fever, and headache. Preclinical and clinical studies were conducted to further investigate the biologic and clinical activities of this herbal medicine. To ensure standardization and maintain interbatch reliability of PHY906, high performance liquid chromatography (HPLC) was used to establish a "chemical fingerprint" of PHY906. In vivo preclinical studies using the murine Colon 39 tumor model showed that PHY906 protected against the weight loss associated with irinotecan treatment. In the presence of PHY906, mice were able to tolerate otherwise lethal doses of irinotecan. Significantly improved antitumor activity and overall survival were observed in animals treated with the combination of irinotecan and PHY906 versus irinotecan alone. The combination of PHY906 with irinotecan, 5-fluorouracil (5-FU), and leucovorin (LV) also resulted in at least additive antitumor activity with no increased host toxicity. Based on these in vivo studies, a phase I multicenter, double-blind, randomized, placebo-controlled, dose escalation, cross-over study of PHY906 as a modulator of the weekly, bolus regimen of irinotecan, 5-FU, and LV (IFL) in the first-line treatment of patients with advanced colorectal cancer (CRC) was conducted. The specific objectives of this clinical trial were to determine the safety and tolerability of PHY906 when administered concomitantly with the bolus, weekly IFL regimen. Treatment with PHY906 did not alter the pharmacokinetics of 5-FU, irinotecan, or the irinotecan metabolite SN-38.
AB - PHY906 is a novel Chinese herbal preparation that has been used in the Orient for over 1800 years to treat a wide range of gastrointestinal side effects including diarrhea, abdominal cramps, vomiting, fever, and headache. Preclinical and clinical studies were conducted to further investigate the biologic and clinical activities of this herbal medicine. To ensure standardization and maintain interbatch reliability of PHY906, high performance liquid chromatography (HPLC) was used to establish a "chemical fingerprint" of PHY906. In vivo preclinical studies using the murine Colon 39 tumor model showed that PHY906 protected against the weight loss associated with irinotecan treatment. In the presence of PHY906, mice were able to tolerate otherwise lethal doses of irinotecan. Significantly improved antitumor activity and overall survival were observed in animals treated with the combination of irinotecan and PHY906 versus irinotecan alone. The combination of PHY906 with irinotecan, 5-fluorouracil (5-FU), and leucovorin (LV) also resulted in at least additive antitumor activity with no increased host toxicity. Based on these in vivo studies, a phase I multicenter, double-blind, randomized, placebo-controlled, dose escalation, cross-over study of PHY906 as a modulator of the weekly, bolus regimen of irinotecan, 5-FU, and LV (IFL) in the first-line treatment of patients with advanced colorectal cancer (CRC) was conducted. The specific objectives of this clinical trial were to determine the safety and tolerability of PHY906 when administered concomitantly with the bolus, weekly IFL regimen. Treatment with PHY906 did not alter the pharmacokinetics of 5-FU, irinotecan, or the irinotecan metabolite SN-38.
KW - Chemotherapy
KW - Chinese herbal medicine
KW - Irinotecan
KW - Metastatic colorectal cancer
KW - Modulator of toxicity
KW - PHY906
KW - Side effects
UR - http://www.scopus.com/inward/record.url?scp=79959336608&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959336608&partnerID=8YFLogxK
U2 - 10.1016/j.clcc.2011.03.003
DO - 10.1016/j.clcc.2011.03.003
M3 - Article
C2 - 21859559
AN - SCOPUS:79959336608
SN - 1533-0028
VL - 10
SP - 85
EP - 96
JO - Clinical Colorectal Cancer
JF - Clinical Colorectal Cancer
IS - 2
ER -