PHI-35: A PHASE I STUDY OF THE TOXICITIES, BIOLOGIC AND CLINICAL EFFECTS OF DAIL

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 本研究的目的是确定一种研究药物5-氮杂2 '脱氧胞苷（DAC）的最高剂量，该剂量可以每周给药5天，持续5周，而不会引起无法控制的副作用（最大耐受剂量，MTD）。另一个目的是收集有关DAC剂量的初步信息，这些剂量对控制肿瘤生长的肿瘤产生的物质有影响。另一个目的是研究以本研究中使用的剂量和时间表给药时，随时间推移保留在体内的DAC水平。 当癌症发生转移且标准化疗药物无效时，认为使用研究药物是合理的。DAC是一种研究药物，似乎通过逆转（变回正常）癌细胞DNA的潜在致癌变化来发挥作用。实验室研究表明，通过逆转这些变化，可以减缓或停止癌细胞的生长。这种工作方式不同于其他杀死细胞并缩小或消除癌症的化疗药物。DAC已用于白血病的治疗研究，并已看到一些反应。它也在较小程度上用于其他类型癌症的治疗研究。在短时间内给予高剂量的DAC并不能缩小肿瘤。这项研究将评估在较长时间内以较低剂量给予DAC是否可能改变肿瘤中导致癌细胞生长的物质水平，从而防止癌细胞在体内生长。为了实现这一目的，将招募可接受重复活检的肿瘤受试者，以便进行实验室检查，以观察DAC是否会引起可能影响肿瘤生长的癌细胞变化。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The purpose of this study is to determine the highest amount of an investigational drug, 5-Aza 2'Deoxycytidine (DAC), that can be given five days a week for five weeks without causing unmanageable side effects (the maximum tolerated dose, MTD). Another purpose is to collect preliminary information about doses of DAC that have an effect on the substances produced by tumors that control tumor growth. Another purpose is to study the levels of DAC that remain in the body over time when given at the doses and schedule used in this study. When cancer has metastasized and standard chemotherapeutic agents are ineffective, it is considered reasonable to use investigational drugs. DAC is an investigational drug that appears to act by reversing (changing back to normal) potentially cancer-causing changes in DNA of cancerous cells. Laboratory studies suggest that, by reversing these changes, the growth of cancer cells can be slowed down or stopped. This way of working is different from other chemotherapy drugs that kill cells and shrink or eliminate cancer. DAC has been used in treatment studies for leukemia, and some responses have been seen. It has also been used to a lesser extent in treatment studies in other types of cancer. DAC given at high doses over a short period of time did not work to shrink tumors. This study will evaluate whether giving DAC at lower doses for a longer period of time might change the levels of substances in tumors that cause the cancer cells to grow and so prevent cancer cells from growing in the body. To accomplish this purpose subjects with tumors that can undergo repeated biopsies will be enrolled so that laboratory tests can be done to see whether DAC causes changes in cancer cells that might have an effect on tumor growth.