PHY-906, a Chinese medicinal formulation, first described about 1500 years ago, is claimed to be useful for the treatment of diarrhea, subcardiac distention, abdominal spasms, fever, headache, vomiting, nausea and extreme thirst. Since some of these conditions are common side effects of chemotherapy, this raised the possibility of using PHY-906 to alleviate these conditions, thereby improving the quality-of -life for cancer patients without compromising the anticancer effect. Tumor bearing mice treated with CPT-11 were used as a model to test this hypothesis. PHY-906 was found useful to decrease the lethality and weight loss caused by CPT-11 in mice whereas antitumor activity of CPT-11 was enhanced . However, the pancytopenia caused by CPT-11 treatment was not altered. The schedule of drug administration has been shown to be very important. Pharmacokinetics studies indicated that PHY-906 increased plasma, but not liver or tumor, AUCs of CPT-11 and its active metabolite, SN-38. This formulation was also found to enhance the therapeutic index of 5-FU, VP-16, L(-)OddC and 5-FU/LV. The impact of PHY-906 on apoptosis, cell stress, cell survival and cell cycle progression was explored. Little variation in the quality of PHY-906 batches have been ascertained by both chemical and biological analyses. Given the consistency of preparations, the claimed clinical usage for thousands of years and encouraging results of these laboratory studies, PHY-906 will be further explored in the clinic to alleviate toxicity associated with chemotherapy in cancer patients. |