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Poster Display session 1

3370 - Influence of cow’s milk on the absorption and exposure of erlotinib in NSCLC patients


28 Sep 2019


Poster Display session 1


Tumour Site

Non-Small Cell Lung Cancer


Geerten Veerman


Annals of Oncology (2019) 30 (suppl_5): v602-v660. 10.1093/annonc/mdz260


G.D.M. Veerman1, K.G.A.M. Hussaarts1, R. Peric2, E. Oomen-de Hoop1, K. Landa1, C.H. Van Der Leest3, S.D. Broerse4, H.B. Rutten5, M.S. Paats2, T. van Gelder6, S.L. Koolen1, J.G. Aerts2, R.W. van Leeuwen6, R.H. Mathijssen1

Author affiliations

  • 1 Medical Oncology, Erasmus MC Cancer Institute, 3015 GD - Rotterdam/NL
  • 2 Pulmonology, Erasmus MC, 3015 GD - Rotterdam/NL
  • 3 Pulmonology, Amphia Ziekenhuis-location Molengracht, 4818 CK - Breda/NL
  • 4 Pulmonology, Franciscus Gasthuis & Vlietland Hospital, Rotterdam/NL
  • 5 Longziekten Dept, Bravis Ziekenhuis-Roosendaal, 4708 AE - Roosendaal/NL
  • 6 Hospital Pharmacy, Erasmus MC, 3015 GD - Rotterdam/NL


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Abstract 3370


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.


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).


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.


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.




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.

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