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.

Inclusion Criteria

Patients must:

• be between 18 and 75 years of age, inclusive, at the time of enrollment.
• have advanced colorectal carcinoma, which may be either measurable or non-measurable.
• not have received either CPT-11, FU, or other cytotoxic chemotherapy agents in any setting (including adjuvant) within 1 year prior to screening.
• have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• use an effective contraceptive method if the patients are of reproductive potential while enrolled in the study, since the potential effects of the herbs on a developing fetus are unknown.
• have an estimated life expectancy of at least 20 weeks.
• provide written informed consent.
• have adequate organ function as indicated by the following laboratory values; these laboratory values must be obtained within 14 days prior to study enrollment:
• Bone marrow reserve: absolute granulocyte count (AGC) more than or equal to 1.5 X 10(to the power of 9)/L, platelet count more than or equal to 100 X 10 (to the power of 9)/L, and hemoglobin level more than or equal to 9 g/dL.
• Hepatic function: serum total bilirubin concentration no greater than 1.5 mg/dL, aspartate transaminase (AST or serum glutamic-oxaloacetic transaminase [SGOT]), and alanine transaminase (ALT or serum glutamic-pyruvic transaminase [SGPT]) levels no greater than grade 2 toxicity as determined from the NCI-CTC version 2.0.
• Renal function: serum creatinine level no greater than grade 2 toxicity as determined from the CTC version 2.0.

Exclusion Criteria

Patients who have or are:

• Gilbert syndrome (familial, non-hemolytic, acholuric jaundice).
• patients with enterostomies.
• untreated brain metastases or deteriorating neurological function after the completion of cranial irradiation.
• a woman who is currently pregnant and/or breast-feeding.
• active infections or any serious systemic disorder that, in the opinion of the principal investigator, are incompatible with the study product and/or procedures.
• used an investigational agent within 4 weeks of study entry.
• a known hypersensitivity to the study medication, its excipients, its analogs, or any of the component herbs.