Toxicity burden score: a novel approach to summarize multiple toxic effects.
Ann Oncol
; 23(2): 537-41, 2012 Feb.
Article
en En
| MEDLINE
| ID: mdl-21536663
BACKGROUND: Toxicity data from cancer trials are summarized into a single outcome, dose-limiting toxicity (DLT), which does not account for multiple lower grade toxic effects nor differentiates between toxicity types and gradations within DLT. METHODS: Toxicity data were summarized into a toxicity burden score (TBS) using a weighted sum. The severity weights were estimated via regression using historical data. We demonstrated the method using historical data from a bortezomib trial and illustrated the advantages of defining DLT based on TBS in a simulated dose-finding trial. RESULTS: The estimated weights were 0.17, 0.40 and 0.85 for grade 1/2, grade 3 and grade 4 platelets, respectively; 0.19, 0.64, 1.03 and 2.53 for grade 1, 2, 3 and 4 neuropathy, respectively and 0.17 for each grade 3 or higher nonhematologic toxic effects unrelated to treatment. In the simulated trial, the probability of selecting doses above the maximum tolerated dose decreased when using the DLT defined based on TBS. CONCLUSIONS: TBS is a feasible approach to summarize toxicity. It includes information from the grades and types of multiple toxic effects and can be applied in all phases of drug development. Further efforts should focus on validating the method in a large prospective study before applying it in practice.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirazinas
/
Ácidos Borónicos
/
Pruebas de Toxicidad
/
Neoplasias
/
Antineoplásicos
Tipo de estudio:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Aspecto:
Patient_preference
Límite:
Humans
Idioma:
En
Revista:
Ann Oncol
Asunto de la revista:
NEOPLASIAS
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Reino Unido