Abstract 3370
Background
Erlotinib is an oral EGFR tyrosine kinase inhibitor used in NSCLC. Drug absorption depends largely on its solubility in the stomach and gastrointestinal tract. Potentially, erlotinib -as lipophilic drug- is ought to dissolve better in a fatty drink such as full cow’s milk compared to water. Gastric acid reducing agents like proton pump inhibitors (PPIs) decrease the solubility and thus the uptake of erlotinib. Hence, we hypothesized that administration of cow’s milk may be a feasible way to increase erlotinib uptake (both with or without PPI co-administration). We performed a two-period randomized cross-over study to investigate the influence of full cow’s milk compared to water on the exposure of erlotinib with and without the PPI esomeprazole in NSCLC patients.
Methods
During 24 hours, pharmacokinetic sampling (PK) was performed at days 7 and 14. In the 7 days prior to PK, erlotinib was taken daily with either 250 mL water or full cow’s milk. Patients were assigned whether to receive erlotinib with (arm A) or without esomeprazole (40mg qd; arm B) 3 hours prior to erlotinib intake starting 3 days prior to PK. Primary endpoint was change in geometric mean for the area under the curve (AUC0-24h). A linear mixed model was used to analyze AUCs and maximal concentration (Cmax).
Results
Twelve of the 20 patients used erlotinib without a PPI. Erlotinib AUC0-24h decreased non-significantly with 5% (95%CI: -14 to + 5%; P = 0.3) when administered with milk compared to water in the non-PPI patients. Also in the 8 patients who did use esomeprazole, erlotinib AUC0-24h did not differ between intake with water or milk (95%CI: -29 to + 40%; P = 1.0). Cmax did not differ in non-PPI users (P = 0.6) and in PPI users (P = 0.9). However, esomeprazole decreased erlotinib AUC0-24h with 48% (95%CI: -61 to -31%; P < 0.001) and Cmax with 55% (95%CI: -66 to -42%; P < 0.001) in 7 patients who completed both arms. No differences in toxicities were observed.
Conclusions
Exposure to erlotinib did not change by erlotinib intake with milk compared to water in both the PPI and non-PPI patients. Therefore, the combination with milk instead of water is safe and well tolerated. Esomeprazole strongly decreased both erlotinib AUC0-24h and Cmax, and should be avoided if possible.
Clinical trial identification
NTR 6148.
Editorial acknowledgement
Legal entity responsible for the study
Ron H.J. Mathijssen.
Funding
Roche.
Disclosure
R.H. Mathijssen: Research grant / Funding (institution): Roche; Research grant / Funding (institution), Travel / Accommodation / Expenses: Astellas; Research grant / Funding (institution): Boehringer; Research grant / Funding (institution): Cristal Therapeutics; Honoraria (self), Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Pamgene; Research grant / Funding (institution), Travel / Accommodation / Expenses: Pfizer; Research grant / Funding (institution): Sanofi; Honoraria (self): Servier; Research grant / Funding (institution): Bayer. All other authors have declared no conflicts of interest.
Resources from the same session
5344 - Global trends in population-based survival for 303,169 adults diagnosed with glioblastoma in 44 countries during 2000-2014 (CONCORD-3)
Presenter: Fabio Girardi
Session: Poster Display session 1
Resources:
Abstract
3088 - Spanish Survey of treatment recommendations for elderley patients with glioblastoma
Presenter: María Ángeles Vaz Salgado
Session: Poster Display session 1
Resources:
Abstract
3484 - Updated analysis of the National Registry of Nervous System Tumors in Spain (RETSINE). RETSINE: National Registry of Nervous System Tumors of the Spanish Research Group in Neuro-oncology (GEINO) and Spanish Infrequent and Orphan Tumors Group (GETHI)
Presenter: Isaac Ceballos Lenza
Session: Poster Display session 1
Resources:
Abstract
4737 - Development and validation of novel nomograms predicting survival of malignant ependymoma patients: A population-based study
Presenter: Alzhraa Abbas
Session: Poster Display session 1
Resources:
Abstract
4740 - Characteristics, incidence, and survival of primary cerebral lymphoma: A population based study
Presenter: Sherief Ghozy
Session: Poster Display session 1
Resources:
Abstract
5362 - Trends in Incidence and Survival Analyses of Adult-onset Medulloblastoma
Presenter: Feifei Lin
Session: Poster Display session 1
Resources:
Abstract
3868 - Meta of classical chemotherapy compared with high-dose chemotherapy combined with autologous stem cell transplantation in newly diagnosed medulloblastoma patients after radiotherapy
Presenter: Mengting Zhang
Session: Poster Display session 1
Resources:
Abstract
4446 - Effect of cumulative dose of maintenance temozolomide on overall survival in patients with high grade glia tumors: a single institution analysis
Presenter: Marta Nerone
Session: Poster Display session 1
Resources:
Abstract
5119 - Markers of systemic inflammation correlate with survival prognosis in patients with newly diagnosed brain metastases
Presenter: Angelika Starzer
Session: Poster Display session 1
Resources:
Abstract
3882 - Venous Thromboembolism and Intracranial Hemorrhage in Patients with High-grade Glioma
Presenter: Clara Borges
Session: Poster Display session 1
Resources:
Abstract