Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric Acute Lymphocytic Leukemia (ALL)

Review from an International Consensus Conference

Terzah M. Horton, Richard Sposto, Patrick Brown, C. Patrick Reynolds, Stephen P. Hunger, Naomi J. Winick, Elizabeth A. Raetz, William L. Carroll, Robert J. Arceci, Michael J. Borowitz, Paul S. Gaynon, Lia Gore, Sima Jeha, Barry J. Maurer, Stuart E. Siegel, Andrea Biondi, Pamela R. Kearns, Aru Narendran, Lewis B. Silverman, Malcolm A. Smith & 2 others C. Michel Zwaan, James A. Whitlock

Research output: Contribution to journalArticle

15 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)872-878
Number of pages7
JournalPediatric Blood and Cancer
Volume54
Issue number7
DOIs
StatePublished - Jul 1 2010

Fingerprint

Precursor Cell Lymphoblastic Leukemia-Lymphoma
Pediatrics
Drug Therapy
Clinical Trials
Pharmaceutical Preparations
Safety
Therapeutics

Keywords

  • ALL
  • ALL relapse
  • Developmental therapeutics
  • Dose-limiting toxicity
  • Maximum tolerated dose

ASJC Scopus subject areas

  • Oncology
  • Pediatrics, Perinatology, and Child Health
  • Hematology

Cite this

Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric Acute Lymphocytic Leukemia (ALL) : Review from an International Consensus Conference. / Horton, Terzah M.; Sposto, Richard; Brown, Patrick; Reynolds, C. Patrick; Hunger, Stephen P.; Winick, Naomi J.; Raetz, Elizabeth A.; Carroll, William L.; Arceci, Robert J.; Borowitz, Michael J.; Gaynon, Paul S.; Gore, Lia; Jeha, Sima; Maurer, Barry J.; Siegel, Stuart E.; Biondi, Andrea; Kearns, Pamela R.; Narendran, Aru; Silverman, Lewis B.; Smith, Malcolm A.; Zwaan, C. Michel; Whitlock, James A.

In: Pediatric Blood and Cancer, Vol. 54, No. 7, 01.07.2010, p. 872-878.

Research output: Contribution to journalArticle

Horton, TM, Sposto, R, Brown, P, Reynolds, CP, Hunger, SP, Winick, NJ, Raetz, EA, Carroll, WL, Arceci, RJ, Borowitz, MJ, Gaynon, PS, Gore, L, Jeha, S, Maurer, BJ, Siegel, SE, Biondi, A, Kearns, PR, Narendran, A, Silverman, LB, Smith, MA, Zwaan, CM & Whitlock, JA 2010, 'Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric Acute Lymphocytic Leukemia (ALL): Review from an International Consensus Conference', Pediatric Blood and Cancer, vol. 54, no. 7, pp. 872-878. https://doi.org/10.1002/pbc.22414
Horton, Terzah M. ; Sposto, Richard ; Brown, Patrick ; Reynolds, C. Patrick ; Hunger, Stephen P. ; Winick, Naomi J. ; Raetz, Elizabeth A. ; Carroll, William L. ; Arceci, Robert J. ; Borowitz, Michael J. ; Gaynon, Paul S. ; Gore, Lia ; Jeha, Sima ; Maurer, Barry J. ; Siegel, Stuart E. ; Biondi, Andrea ; Kearns, Pamela R. ; Narendran, Aru ; Silverman, Lewis B. ; Smith, Malcolm A. ; Zwaan, C. Michel ; Whitlock, James A. / Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric Acute Lymphocytic Leukemia (ALL) : Review from an International Consensus Conference. In: Pediatric Blood and Cancer. 2010 ; Vol. 54, No. 7. pp. 872-878.
@article{1232f0fe07ce421396862ef72edbf6fc,
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.",
keywords = "ALL, ALL relapse, Developmental therapeutics, Dose-limiting toxicity, Maximum tolerated dose",
author = "Horton, {Terzah M.} and Richard Sposto and Patrick Brown and Reynolds, {C. Patrick} and Hunger, {Stephen P.} and Winick, {Naomi J.} and Raetz, {Elizabeth A.} and Carroll, {William L.} and Arceci, {Robert J.} and Borowitz, {Michael J.} and Gaynon, {Paul S.} and Lia Gore and Sima Jeha and Maurer, {Barry J.} and Siegel, {Stuart E.} and Andrea Biondi and Kearns, {Pamela R.} and Aru Narendran and Silverman, {Lewis B.} and Smith, {Malcolm A.} and Zwaan, {C. Michel} and Whitlock, {James A.}",
year = "2010",
month = "7",
day = "1",
doi = "10.1002/pbc.22414",
language = "English (US)",
volume = "54",
pages = "872--878",
journal = "Pediatric Blood and Cancer",
issn = "1545-5009",
publisher = "Wiley-Liss Inc.",
number = "7",

}

TY - JOUR

T1 - Toxicity assessment of molecularly targeted drugs incorporated into multiagent chemotherapy regimens for pediatric Acute Lymphocytic Leukemia (ALL)

T2 - Review from an International Consensus Conference

AU - Horton, Terzah M.

AU - Sposto, Richard

AU - Brown, Patrick

AU - Reynolds, C. Patrick

AU - Hunger, Stephen P.

AU - Winick, Naomi J.

AU - Raetz, Elizabeth A.

AU - Carroll, William L.

AU - Arceci, Robert J.

AU - Borowitz, Michael J.

AU - Gaynon, Paul S.

AU - Gore, Lia

AU - Jeha, Sima

AU - Maurer, Barry J.

AU - Siegel, Stuart E.

AU - Biondi, Andrea

AU - Kearns, Pamela R.

AU - Narendran, Aru

AU - Silverman, Lewis B.

AU - Smith, Malcolm A.

AU - Zwaan, C. Michel

AU - Whitlock, James A.

PY - 2010/7/1

Y1 - 2010/7/1

N2 - 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.

AB - 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.

KW - ALL

KW - ALL relapse

KW - Developmental therapeutics

KW - Dose-limiting toxicity

KW - Maximum tolerated dose

UR - http://www.scopus.com/inward/record.url?scp=77951744594&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951744594&partnerID=8YFLogxK

U2 - 10.1002/pbc.22414

DO - 10.1002/pbc.22414

M3 - Article

VL - 54

SP - 872

EP - 878

JO - Pediatric Blood and Cancer

JF - Pediatric Blood and Cancer

SN - 1545-5009

IS - 7

ER -