Dactinomycin and vincristine toxicity in the treatment of childhood cancer: A retrospective study from the Children's Oncology Group

Bryan Langholz, Jeffrey M. Skolnik, Jeffrey S. Barrett, Jamie Renbarger, Nita L. Seibel, Anne Zajicek, Carola A S Arndt

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: Dactinomycin (AMD) and vincristine (VCR) have been used for the treatment of childhood cancer over the past 40 years but evidence-based dosing guidance is lacking. Methods: Patient AMD and VCR dose and drug-related adverse event (AE) information from four rhabdomyosarcoma (RMS) and two Wilms tumor (WT) studies were assembled. Statistical modeling was used to account for differences in AE data collection across studies, develop rate models for grade 3/4 CTCAE v3 hepatic- (AMD) and neuro- (VCR) toxicity, assess variation in toxicity rates over age and other factors, and predict toxicity risk under current dosing guidelines. Results: For the same dose/body size, AMD toxicity rates were higher in patients <1 year than older patients and VCR toxicity rates increased with age. The statistical model provided estimates for AMD and VCR toxicity risk under current dosing schedules and indicated that patients of smaller body size were at lower risk of VCR toxicity than larger patients of the same age. The rate of AMD toxicity was highest early in treatment and was lower in patients who tolerated initial AMD without toxicity. Conclusion: The observed decrease in AMD toxicity rate with cumulative dose may indicate sensitivity in a subgroup of patients while the observed increase in VCR toxicity risk with age may indicate changing sensitivity to VCR. Current dosing practices result in a fairly uniform toxicity profile within age group. However, PK/PD studies should be done to provide further provide further information on best dosing guidelines.

Original languageEnglish
Pages (from-to)252-257
Number of pages6
JournalPediatric Blood and Cancer
Volume57
Issue number2
DOIs
StatePublished - Aug 2011

Fingerprint

Dactinomycin
Vincristine
Retrospective Studies
Neoplasms
Body Size
Therapeutics
Guidelines
Wilms Tumor
Rhabdomyosarcoma
Age Factors
Statistical Models
Drug-Related Side Effects and Adverse Reactions
Appointments and Schedules
Age Groups
Liver

Keywords

  • Hepatic toxicity
  • Neuropathy
  • Rhabdomyosarcoma
  • Risk estimation
  • Wilms tumor

ASJC Scopus subject areas

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

Cite this

Dactinomycin and vincristine toxicity in the treatment of childhood cancer : A retrospective study from the Children's Oncology Group. / Langholz, Bryan; Skolnik, Jeffrey M.; Barrett, Jeffrey S.; Renbarger, Jamie; Seibel, Nita L.; Zajicek, Anne; Arndt, Carola A S.

In: Pediatric Blood and Cancer, Vol. 57, No. 2, 08.2011, p. 252-257.

Research output: Contribution to journalArticle

Langholz, Bryan ; Skolnik, Jeffrey M. ; Barrett, Jeffrey S. ; Renbarger, Jamie ; Seibel, Nita L. ; Zajicek, Anne ; Arndt, Carola A S. / Dactinomycin and vincristine toxicity in the treatment of childhood cancer : A retrospective study from the Children's Oncology Group. In: Pediatric Blood and Cancer. 2011 ; Vol. 57, No. 2. pp. 252-257.
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abstract = "Background: Dactinomycin (AMD) and vincristine (VCR) have been used for the treatment of childhood cancer over the past 40 years but evidence-based dosing guidance is lacking. Methods: Patient AMD and VCR dose and drug-related adverse event (AE) information from four rhabdomyosarcoma (RMS) and two Wilms tumor (WT) studies were assembled. Statistical modeling was used to account for differences in AE data collection across studies, develop rate models for grade 3/4 CTCAE v3 hepatic- (AMD) and neuro- (VCR) toxicity, assess variation in toxicity rates over age and other factors, and predict toxicity risk under current dosing guidelines. Results: For the same dose/body size, AMD toxicity rates were higher in patients <1 year than older patients and VCR toxicity rates increased with age. The statistical model provided estimates for AMD and VCR toxicity risk under current dosing schedules and indicated that patients of smaller body size were at lower risk of VCR toxicity than larger patients of the same age. The rate of AMD toxicity was highest early in treatment and was lower in patients who tolerated initial AMD without toxicity. Conclusion: The observed decrease in AMD toxicity rate with cumulative dose may indicate sensitivity in a subgroup of patients while the observed increase in VCR toxicity risk with age may indicate changing sensitivity to VCR. Current dosing practices result in a fairly uniform toxicity profile within age group. However, PK/PD studies should be done to provide further provide further information on best dosing guidelines.",
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