title: Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric acute lymphocytic leukemia (ALL): review from an international consensus conference.
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.
authors.affiliation: Texas Children's Cancer Center/Baylor College of Medicine, Houston, Texas 77030, USA. tmhorton@txccc.org
authors.forename: Terzah M
authors.initials: TM
authors.lastname: Horton
authors.forename: Richard
authors.initials: R
authors.lastname: Sposto
authors.forename: Patrick
authors.initials: P
authors.lastname: Brown
authors.forename: C Patrick
authors.initials: CP
authors.lastname: Reynolds
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
authors.forename: Naomi J
authors.initials: NJ
authors.lastname: Winick
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Raetz
authors.forename: William L
authors.initials: WL
authors.lastname: Carroll
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Arceci
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Borowitz
authors.forename: Paul S
authors.initials: PS
authors.lastname: Gaynon
authors.forename: Lia
authors.initials: L
authors.lastname: Gore
authors.forename: Sima
authors.initials: S
authors.lastname: Jeha
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Maurer
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Siegel
authors.forename: Andrea
authors.initials: A
authors.lastname: Biondi
authors.forename: Pamela R
authors.initials: PR
authors.lastname: Kearns
authors.forename: Aru
authors.initials: A
authors.lastname: Narendran
authors.forename: Lewis B
authors.initials: LB
authors.lastname: Silverman
authors.forename: Malcolm A
authors.initials: MA
authors.lastname: Smith
authors.forename: C Michel
authors.initials: CM
authors.lastname: Zwaan
authors.forename: James A
authors.initials: JA
authors.lastname: Whitlock
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D002648:Child; D002986:Clinical Trials as Topic; D006801:Humans; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*