Yale University School of Medicine, Section of Medical Oncology, 333 Cedar Street, FMP 116 New Haven, CT 06520, USA.
Phytomedicine. 2010 Mar;17(3-4):161-9. doi: 10.1016/j.phymed.2009.12.016. Epub 2010 Jan 22.
The botanical formulation, PHY906, has been used widely in Eastern countries to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. PHY906 may also have anti-tumor properties and may potentiate the action of several chemotherapeutic agents based on pre-clinical studies. We conducted a Phase I study using PHY906 in combination with capecitabine in patients with advanced pancreatic and gastrointestinal malignancies to determine the maximum tolerated dose (MTD) of capecitabine in combination with PHY906.
This study was a single institution, open-label, Phase I study of PHY906 800mg BID on days 1-4 in combination with escalating doses of capecitabine (1000, 1250, 1500, and 1750mg/m(2)) orally twice daily on days 1-7 of a 14-day cycle (7/7 schedule). Capecitabine was increased until the appearance of dose limiting toxicities (DLTs). Measurements of efficacy included tumor response by Response Evaluation Criteria in Solid Tumors (RECIST).
Twenty-four patients with a median age of 67 years (range 40-84) with pancreatic cancer (15), colon cancer (6), cholangiocarcinoma (1), esophageal cancer (1) and unknown primary (1) received a total of 116 cycles (median 5 cycles; range 1-17 cycles) over 4 dose levels of capecitabine. One DLT (Grade 4 AST/ALT, Grade 3 hyponatremia) was observed in the 1000mg/m(2) cohort of patients. No further DLT was observed in the subsequent cohorts and doses of capecitabine were escalated to 1750mg/m(2) BID. There were no DLTs at the maximum dose level of 1750mg/m(2), however, the delivered dose-intensity of capecitabine was similar at the 1750mg/m(2) dose level as the 1500mg/m(2) dose level. Therefore, the MTD was defined at 1500mg/m(2) of capecitabine in this dosing schedule with PHY906. One patient achieved a partial response, and 13 patients had stable disease that lasted more than six weeks.
The MTD of capecitabine was determined to be 1500mg/m(2) BID administered in a 7/7 schedule, in combination with PHY906 800mg BID on days 1-4. This combination was well tolerated and warrants further study.
植物制剂 PHY906 已在东方国家广泛用于治疗胃肠道症状，包括腹泻、恶心和呕吐。PHY906 还可能具有抗肿瘤特性，并可能基于临床前研究增强几种化疗药物的作用。我们进行了一项 I 期研究，在晚期胰腺和胃肠道恶性肿瘤患者中联合使用 PHY906 和卡培他滨，以确定联合使用 PHY906 时卡培他滨的最大耐受剂量（MTD）。
这是一项单机构、开放性、I 期 PHY906 800mg BID 研究，每天 1-4 天用药，同时每天 1-7 天口服递增剂量的卡培他滨（1000、1250、1500 和 1750mg/m²），每 14 天为一个周期（7/7 方案）。卡培他滨的剂量增加直到出现剂量限制毒性（DLT）。通过实体瘤反应评估标准（RECIST）测量疗效，包括肿瘤反应。
24 名中位年龄为 67 岁（范围为 40-84 岁）的胰腺癌（15 例）、结肠癌（6 例）、胆管癌（1 例）、食管癌（1 例）和不明原发灶癌（1 例）患者接受了总计 116 个周期（中位 5 个周期；范围为 1-17 个周期），共 4 个卡培他滨剂量水平。在 1000mg/m²的患者队列中观察到 1 例 DLT（AST/ALT 级 4，低钠血症级 3）。随后的队列中未观察到其他 DLT，并将卡培他滨剂量递增至 1750mg/m² BID。在 1750mg/m² 的最大剂量水平下未观察到 DLT，但 1750mg/m² 剂量水平的卡培他滨给药强度与 1500mg/m² 剂量水平相似。因此，在这种给药方案中，卡培他滨的 MTD 定义为 1500mg/m²。1 例患者获得部分缓解，13 例患者的疾病稳定超过六周。
确定 PHY906 每天 1-4 天 800mg BID 联合卡培他滨 1500mg/m² BID 的最大耐受剂量，每天 1-7 天 7/7 方案。这种联合用药耐受性良好，值得进一步研究。
