Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric acute lymphocytic leukemia (ALL): review from an international consensus conference.
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.
Horton
Terzah M
TM
Texas Children's Cancer Center/Baylor College of Medicine, Houston, Texas 77030, USA. tmhorton@txccc.org
Sposto
Richard
R
Brown
Patrick
P
Reynolds
C Patrick
CP
Hunger
Stephen P
SP
Winick
Naomi J
NJ
Raetz
Elizabeth A
EA
Carroll
William L
WL
Arceci
Robert J
RJ
Borowitz
Michael J
MJ
Gaynon
Paul S
PS
Gore
Lia
L
Jeha
Sima
S
Maurer
Barry J
BJ
Siegel
Stuart E
SE
Biondi
Andrea
A
Kearns
Pamela R
PR
Narendran
Aru
A
Silverman
Lewis B
LB
Smith
Malcolm A
MA
Zwaan
C Michel
CM
Whitlock
James A
JA
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*