Predicting tumour growth and its impact on survival in gemcitabine-treated patients with advanced pancreatic cancer.
Eur J Pharm Sci
; 115: 296-303, 2018 Mar 30.
Article
in En
| MEDLINE
| ID: mdl-29366960
ABSTRACT
The aim of this evaluation was to characterize the impact of the tumour size (TS) effects driven by the anticancer drug gemcitabine on overall survival (OS) in patients with advanced pancreatic cancer by building and validating a predictive semi-mechanistic joint TS-OS model. TS and OS data were obtained from one phase II and one phase III study where gemcitabine was administered (1000-1250â¯mg/kg over 30-60â¯min i.v infusion) as single agent to patients (nâ¯=â¯285) with advanced pancreatic cancer. Drug exposure, TS and OS were linked using the population approach with NONMEM 7.3. Pancreatic tumour progression was characterized by exponential growth (doubling timeâ¯=â¯67â¯weeks), and tumour response to treatment was described as a function of the weekly area under the gemcitabine triphosphate concentration vs time curve (AUC), including treatment-related resistance development. The typical predicted percentage of tumour growth inhibition with respect to no treatment was 22.3% at the end of 6 chemotherapy cycles. Emerging resistance elicited a 57% decrease in drug effects during the 6th chemotherapy cycle. Predicted TS profile was identified as main prognostic factor of OS, with tumours responders' profiles improving median OS by 30â¯weeks compared to stable-disease TS profiles. Results of NCT00574275 trial were predicted using this modelling framework, thereby validating the approach as a prediction tool in clinical development. Our analyses show that despite the advanced stage of the disease in this patient population, the modelling framework herein can be used to predict the likelihood of treatment success using early clinical data.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
Deoxycytidine
/
Cell Proliferation
/
Antineoplastic Agents
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Adult
/
Aged
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Aged80
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Eur J Pharm Sci
Journal subject:
FARMACIA
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FARMACOLOGIA
/
QUIMICA
Year:
2018
Type:
Article