Method to measure the mismatch between target and achieved received dose intensity of chemotherapy in cancer trials: a retrospective analysis of the MRC BO06 trial in osteosarcoma.
BMJ Open
; 9(5): e022980, 2019 05 30.
Article
em En
| MEDLINE
| ID: mdl-31152023
ABSTRACT
OBJECTIVES:
In cancer studies, the target received dose intensity (tRDI) for any regimen, the intended dose and time for the regimen, is commonly taken as a proxy for achieved RDI (aRDI), the actual individual dose and time for the regimen. Evaluating tRDI/aRDI mismatches is crucial to assess study results whenever patients are stratified on allocated regimen. The manuscript develops a novel methodology to highlight and evaluate tRDI/aRDI mismatches.DESIGN:
Retrospective analysis of a randomised controlled trial, MRC BO06 (EORTC 80931).SETTING:
Population-based study but proposed methodology can be applied to other trial designs.PARTICIPANTS:
A total of 497 patients with resectable high-grade osteosarcoma, of which 19 were excluded because chemotherapy was not started or the estimated dose was abnormally high (>1.25 × prescribed dose).INTERVENTIONS:
Two regimens with the same anticipated cumulative dose (doxorubicin 6×75 mg/m2/week; cisplatin 6×100 mg/m2/week) over different time schedules every 3 weeks in regimen-C and every 2 weeks in regimen-DI. PRIMARY AND SECONDARY OUTCOMEMEASURES:
tRDI distribution was measured across groups of patients derived from k-means clustering of treatment data. K-means creates groups of patients who are aRDI-homogeneous. The main outcome is the proportion of tRDI values in groups of homogeneous aRDI.RESULTS:
For nearly half of the patients, there is a mismatch between tRDI and aRDI; for 21%, aRDI was closer to the tRDI of the other regimen.CONCLUSIONS:
For MRC BO06, tRDI did not predict well aRDI. The manuscript offers an original procedure to highlight the presence of and quantify tRDI/aRDI mismatches. Caution is required to interpret the effect of chemotherapy-regimen intensification on survival outcome at an individual level where such a mismatch is present.The study relevance lies in the use of individual realisation of the intended treatment, which depends on individual delays and/or dose reductions reported throughout the treatment. TRIAL REGISTRATION NUMBER ISRCTN86294690.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Ósseas
/
Protocolos de Quimioterapia Combinada Antineoplásica
/
Osteossarcoma
/
Ensaios Clínicos Controlados Aleatórios como Assunto
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
BMJ Open
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Holanda