Department of Medicine and Pharmacology, Developmental Therapeutics Program, Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA.
Clin Colorectal Cancer. 2011 Jun;10(2):85-96. doi: 10.1016/j.clcc.2011.03.003. Epub 2011 Apr 22.
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.
PHY906 是一种新型中草药制剂，在东方已经使用了 1800 多年，用于治疗广泛的胃肠道副作用，包括腹泻、腹痛、呕吐、发烧和头痛。进行了临床前和临床研究，以进一步研究这种草药的生物学和临床活性。为了确保 PHY906 的标准化和批次间的可靠性，采用高效液相色谱法（HPLC）建立了 PHY906 的“化学指纹图谱”。使用小鼠结肠 39 肿瘤模型的体内临床前研究表明，PHY906 可预防伊立替康治疗引起的体重减轻。在 PHY906 的存在下，小鼠能够耐受否则致命剂量的伊立替康。与单独使用伊立替康相比，用伊立替康和 PHY906 联合治疗的动物观察到显著改善的抗肿瘤活性和总体生存率。PHY906 与伊立替康、5-氟尿嘧啶（5-FU）和亚叶酸（LV）的联合使用也导致抗肿瘤活性至少相加，而宿主毒性没有增加。基于这些体内研究，进行了一项多中心、双盲、随机、安慰剂对照、剂量递增、交叉的 PHY906 作为伊立替康、5-FU 和 LV（IFL）每周推注方案的调节剂的 I 期临床试验，用于一线治疗晚期结直肠癌（CRC）患者。该临床试验的具体目的是确定同时给予推注、每周 IFL 方案时 PHY906 的安全性和耐受性。PHY906 的治疗并未改变 5-FU、伊立替康或伊立替康代谢物 SN-38 的药代动力学。
