IRINOTECAN AND CYTARABINE IN ACUTE MYELOID LEUKEMIA

伊立替康和阿糖胞苷治疗急性髓系白血病

• 批准号: 6378210
• 负责人: MARIA R BAER
• 金额: $ 27.23万
• 依托单位: ROSWELL PARK CANCER INSTITUTE CORP
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2003-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6378210
• 关键词: DNA topoisomerases; acute myelogenous leukemia; carboxylic ester hydrolases; chemical models; clinical research; combination chemotherapy; cytosine arabinoside; drug resistance; enzyme activity; human subject; human therapy evaluation; irinotecan; model design /development; neoplasm /cancer chemotherapy; pharmacokinetics

Treatment outcome has improved in acute myeloid leukemia (AML), AML. To improve treatment outcomes in AML, there is a compelling need to develop treatments which attack novel cellular targets and which are not affected by known mechanisms of resistance. Irinotecan (CPT-11) is a topoisomerase I-interactive drug which, as a single agent, has shown limited activity against 5-florouracil (5-FU)-refractory colorectal cancer, but, in combination with 5-FU, is very effective against the disease both in preclinical models and in clinical trials. The efficacy of this combination is highly schedule-dependent. We have found that CPT-11 is highly active against multidrug-resistant human leukemia xenografts in vivo. Moreover, preclinical data from our laboratory demonstrate that the schedule-dependent synergistic drug interaction which has been found for CPT-11 and 5-FU also applies to CPT-11 in combination with Ara-C. Based on these preclinical findings, a Phase I clinical protocol was designed and initiated combining CPT-11 with Ara-C in the treatment of refractory AML and chronic myelogenous leukemia in myeloid blast transformation (CML-MBT). The objective of this application is to develop CPT-11 and Ara-C combination chemotherapy as a treatment for myeloid leukemias resistant to current therapies; this approach would then subsequently be applied to untreated AML with a low likelihood of response to current regimens. The specific aims presented are: 1. To define the efficacy of CPT-11 and Ara-C combination chemotherapy in refractory AML and in CML-MBT; 2. To optimize the schedule of CPT-11 and Ara-C combination chemotherapy based on laboratory correlates of efficacy; and 3. To identify correlates of sensitivity and resistance to CPT-11 and Ara-C combination chemotherapy.

急性髓性白血病（AML）的治疗效果有所改善，

项目成果

Breast cancer resistance protein (BCRP/MXR/ABCG2) in acute myeloid leukemia: discordance between expression and function.

急性髓系白血病中的乳腺癌耐药蛋白（BCRP/MXR/ABCG2）：表达与功能之间的不一致。

• DOI: 10.1038/sj.leu.2403395
• 发表时间: 2004
• 期刊: Leukemia
• 影响因子: 11.4
• 作者: Suvannasankha,A;Minderman,H;O'Loughlin,KL;Nakanishi,T;Greco,WR;Ross,DD;Baer,MR
• 通讯作者: Baer,MR

In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells.

体外和体内伊立替康诱导急性髓系白血病细胞细胞周期和凋亡相关基因表达谱的变化。

• DOI: 10.1158/1535-7163.mct-04-0048
• 发表时间: 2005
• 期刊: Molecular cancer therapeutics
• 影响因子: 5.7
• 作者: Minderman,Hans;Conroy,JeffreyM;O'Loughlin,KieranL;McQuaid,Devin;Quinn,Paul;Li,Song;Pendyala,Lakshmi;Nowak,NormaJ;Baer,MariaR
• 通讯作者: Baer,MariaR