Toxicity Assessment of Molecularly Targeted Drugs Incorporated into Multiagent Chemotherapy Regimens for Pediatric Acute Lymphocytic Leukemia (ALL): Review From an International Consensus Conference

被引：18

作者：

Horton, Terzah M. ^{[1
]}

Sposto, Richard ^{[2
]}

Brown, Patrick ^{[3
]}

Reynolds, C. Patrick ^{[4
]}

Hunger, Stephen P. ^{[5
]}

Winick, Naomi J. ^{[6
]}

Raetz, Elizabeth A. ^{[7
]}

Carroll, William L. ^{[7
]}

Arceci, Robert J. ^{[3
]}

Borowitz, Michael J. ^{[3
]}

Gaynon, Paul S. ^{[2
]}

Gore, Lia ^{[5
]}

Jeha, Sima ^{[8
]}

Maurer, Barry J. ^{[4
]}

Siegel, Stuart E. ^{[2
]}

Biondi, Andrea ^{[9
]}

Kearns, Pamela R. ^{[10
]}

Narendran, Aru ^{[11
]}

Silverman, Lewis B. ^{[12
]}

Smith, Malcolm A. ^{[13
]}

Zwaan, C. Michel ^{[14
]}

Whitlock, James A. ^{[15
]}

机构：

[1] Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA

[2] Childrens Hosp Los Angeles, USC CHLA Inst Pediat Clin Res, Los Angeles, CA 90027 USA

[3] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA

[4] Texas Tech Univ Hlth Sci Ctr, Ctr Canc, Sch Med, Lubbock, TX USA

[5] Univ Colorado Denver, Sch Med, Childrens Hosp, Aurora, CO USA

[6] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA

[7] NYU, Dept Pediat Oncol, New York, NY USA

[8] St Jude Childrens Hosp, Memphis, TN 38105 USA

[9] Clin Pediat Univ, Ctr M Tettamanti, Milano Bicocca Hosp, Monza, Italy

[10] Univ Birmingham, Inst Canc Studies, Birmingham, W Midlands, England

[11] So Alberta Childrens Canc Program, Calgary, AB, Canada

[12] Childrens Hosp Boston, Dana Farber Canc Inst, Boston, MA USA

[13] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA

[14] Sophia Childrens Univ Hosp, Erasmus Med Ctr, I BFM SG New Agents Working Grp, Rotterdam, Netherlands

[15] Vanderbilt Univ, Dept Pediat, Div Pediat Hematol Oncol, Nashville, TN USA

来源：

PEDIATRIC BLOOD & CANCER | 2010年 / 54卷 / 07期

关键词：

ALL; ALL relapse; developmental therapeutics; dose-limiting toxicity; maximum tolerated dose; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; FLT3; INHIBITOR; THERAPY; PATHWAYS; CHILDREN; RELAPSE; TRIALS; CANCER;

D O I：

10.1002/pbc.22414

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

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. Pediatr Blood Cancer 2010;54:872-878. (C) 2010 Wiley-Liss, Inc.

引用

页码：872 / 878

页数：7

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