Investigating the impact of target lesion selection on drug effect evaluation and tumour growth rate determination using tumour growth inhibition models: Example of malignant pleural mesothelioma patients treated with cisplatin alone or in combination with pemetrexed.
Eur J Pharm Sci
; 161: 105781, 2021 Jun 01.
Article
in En
| MEDLINE
| ID: mdl-33667665
ABSTRACT
In the last update of the RECIST criteria in 2009, it was proposed that the number of target lesions to be followed over time for response-to-treatment assessment be reduced from 10 to 5 lesions maximum, with up to 2 per organ. We explored the impact of reducing the number of target lesion on the assessment of drug effect in a randomised phase III clinical trial using a tumour growth inhibition (TGI) model. Tumour size measurements from 441 (out of 456) patients were used to build two datasets for which observations were the sum of longest diameters of all measurable lesions (ALL dataset) or following the RECIST 1.1 recommendations (R1.1 dataset). TGI models incorporating a categorical covariate for treatment group or a pharmacokinetic metric (i.e. dose; simulated area under the curve) were used to describe the longitudinal tumour size kinetics. Drug exposure was not superior to treatment group at describing drug effect. ALL and R1.1 individual estimates of drug effect appeared to be strongly correlated (r2=0.88). Including pharmacokinetic metrics in TGI models should be conducted carefully when no pharmacokinetic samples are available. Reducing the number of target lesion did not seem to compromise the determination of drug effect using TGI models.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pleural Neoplasms
/
Pharmaceutical Preparations
/
Mesothelioma, Malignant
/
Lung Neoplasms
/
Mesothelioma
Type of study:
Clinical_trials
/
Guideline
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Eur J Pharm Sci
Journal subject:
FARMACIA
/
FARMACOLOGIA
/
QUIMICA
Year:
2021
Document type:
Article