PHARMACOLOGIC AND PHASE I STUDIES OF NEW AGENTS FOR THE TREATMENT OF SOLID TUMORS

“新型抗癌药的药物开发 通常涉及药物作用机制的广泛研究， 生物化学和分子水平。在人类中， 分子实体传统上包括药物的测量 药物动力学和药效学纳入早期I期研究。 然而，细胞内测量药物效应的方法较少 由于研究中存在明显的技术和后勤困难， 人类实验对象此外，有前途的新的 在早期临床试验中未能产生抗癌活性的药物， 经常是未知的。只有通过设计科学合理的临床 将联合收割机传统药代动力学终点与 细胞内药效学测量，我们希望， 更好地了解新药的确切作用， 人类这种方法有望阐明为什么新的治疗方法 在我们的临床试验中进行的研究是否有效。目前我们的 实验室正在应用分析技术，如气体和液体 色谱-质谱检测I相 临床研究。这些研究包括生物化学调节， 氟化嘧啶，使用嘧啶代谢抑制剂， 例如恩尿嘧啶。其他正在进行或计划研究的药物 包括17-烯丙基氨基-17-去甲氧基格尔德霉素，一种新药剂 针对头部休克蛋白和染料木黄酮， 来自大豆的抗癌和生长 抑制特性。最后，由于潜在的影响， 在入组I期研究的患者中使用替代药物， 我们正在研究替代医学的流行程度和类型， 在我们的研究人群中很流行。"

"Drug development of new anticancer agent typically involved extensive studies of drug mechanisms of action at the biochemical and molecular level. In humans, initial studies of ne molecular entities traditionally incorporate measurement of drug pharmacokinetics and pharmacodynamics into early phase I studies. However, intracellular measurement of drug effects are less common due to obvious technical and logistical difficulties in study human subjects. Furthermore, the exact reasons why promising new drugs fail to generate anticancer activity in early clinical trials are frequently unknown. Only by designing scientifically sound clinical trials that combine traditional pharmacokinetic endpoint with intracellular pharmacodynamic measurements can we hope to obtain a better understanding of the precise actions of new drugs in humans. This approach will hopefully elucidate why new treatments under study in our clinical trial do or do not work. Currently, our laboratory is applying analytic techniques such as gas and liquid chromotagraphy with mass spectroscopic detection to phase I clinical studies. These include studies of biochemical modulation of fluorinated pyrimidines, using inhibitors of pyrimidine metabolism, such as eniluracil. Other ongoing or planned agents under study include 17-allylamino-17-demethoxygeldanamycin, a novel agents that targets head shock proteins, and genistein, a natural product derived from soy beans with cancer preventative and growth inhibitory properties. Finally, because of the potential impact of the use of alternative medicines in patients enrolled in phase I studies, we are examining the prevalence and types of alternative medicine popular in our study populations."