Safety Study of the Chemotherapy Modulator PHY906 in Patients With Advanced Colorectal Cancer

The triple combination chemotherapy of irinotecan, 5-fluorouracil and leucovorin (CPT-11/5-FU/LV or Saltz regimen) is the treatment of choice for patients with advanced colorectal cancer. Severe diarrhea, unfortunately, is a side effect of such treatment. Preclinical studies have indicated that the botanical drug PHY906 can reduce such diarrhea without compromising the effectiveness of the chemotherapy. The primary purpose of this clinical study is to evaluate the safety, tolerability and minimum effective dose of PHY906 when administered in conjunction with the Saltz regimen.

CPT-11/5-FU/LV is an active combination agent in the treatment of colorectal cancer, but one of its dose-limiting toxicities is diarrhea. PHY906 has been shown to reduce the severity of CPT-11-induced toxicity without compromising antitumor efficacy in in vivo animal models. Additionally, there has been a long historical experience in the Far East demonstrating safety of PHY906 in humans. Thus, we are conducting this double-blind, placebo-controlled study to evaluate the safety and tolerability of PHY906. This dose escalation study will also examine the effect of PHY906 (1.2, 2.4, and 3.6 g/day) on the pharmacokinetics of CPT-11 and 5-FU after concomitant administration with CPT-11, 5-FU, and LV, and on the severity of CPT-11-induced toxicities such as diarrhea.