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. SmithC. Michel Zwaan, James A. Whitlock

Research output: Contribution to journalReview article

15 Scopus citations

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

Keywords

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

ASJC Scopus subject areas

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

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    Horton, T. M., Sposto, R., Brown, P., Reynolds, C. P., Hunger, S. P., Winick, N. J., Raetz, E. A., Carroll, W. L., Arceci, R. J., Borowitz, M. J., Gaynon, P. S., Gore, L., Jeha, S., Maurer, B. J., Siegel, S. E., Biondi, A., Kearns, P. R., Narendran, A., Silverman, L. B., ... Whitlock, J. A. (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, 54(7), 872-878. https://doi.org/10.1002/pbc.22414