多药联合化疗方案中纳入的分子靶向药物治疗儿童急性淋巴细胞白血病（ALL）的毒性评估：国际共识会议综述。
Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric acute lymphocytic leukemia (ALL): review from an international consensus conference.
机构信息
Texas Children's Cancer Center/Baylor College of Medicine, Houston, Texas 77030, USA.
出版信息
Pediatr Blood Cancer. 2010 Jul 1;54(7):872-8. doi: 10.1002/pbc.22414.
Abstract
One of the challenges of incorporating molecularly targeted drugs into multi-agent chemotherapy (backbone) regimens is defining dose-limiting toxicities (DLTs) of the targeted agent against the background of toxicities of the backbone regimen. An international panel of 22 pediatric acute lymphocytic leukemia (ALL) experts addressed this issue (www.ALLNA.org). Two major questions surrounding DLT assessment were explored: (1) how toxicities can be best defined, assessed, and attributed; and (2) how effective dosing of new agents incorporated into multi-agent ALL clinical trials can be safely established in the face of disease- and therapy-related systemic toxicities. The consensus DLT definition incorporates tolerance of resolving Grade 3 and some resolving Grade 4 toxicities with stringent safety monitoring. This functional DLT definition is being tested in two Children's Oncology Group (COG) ALL clinical trials.
摘要
将分子靶向药物纳入多药化疗（骨干）方案的挑战之一是在骨干方案毒性的背景下定义靶向药物的剂量限制毒性（DLT）。一个由 22 名儿科急性淋巴细胞白血病（ALL）专家组成的国际小组解决了这个问题（www.ALLNA.org）。围绕 DLT 评估有两个主要问题：（1）如何最好地定义、评估和归因毒性；（2）如何在疾病和治疗相关的全身毒性的情况下安全地建立新药物纳入多药 ALL 临床试验的有效剂量。共识 DLT 定义包括耐受缓解 3 级和一些严格安全监测的缓解 4 级毒性。这个功能 DLT 定义正在两个儿童肿瘤学组（COG）ALL 临床试验中进行测试。
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1
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Clin Cancer Res. 2009 Feb 15;15(4):1126-32. doi: 10.1158/1078-0432.CCR-08-0144.
2
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J Clin Oncol. 2008 Aug 20;26(24):3971-8. doi: 10.1200/JCO.2008.16.1414.
3
Molecularly targeted therapies for pediatric acute myeloid leukemia: progress to date.儿童急性髓系白血病的分子靶向治疗：迄今进展
Paediatr Drugs. 2008;10(2):85-92. doi: 10.2165/00148581-200810020-00003.
4
The therapeutic potential of the proteasome in leukaemia.蛋白酶体在白血病中的治疗潜力。
Hematol Oncol. 2008 Jun;26(2):73-81. doi: 10.1002/hon.848.
5
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