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Randomized Controlled Trial
. 2021 Jan;60(1):69-77.
doi: 10.1007/s40262-020-00910-1.

Influence of Cow's Milk and Esomeprazole on the Absorption of Erlotinib: A Randomized, Crossover Pharmacokinetic Study in Lung Cancer Patients

G D Marijn Veerman  1 , Koen G A M Hussaarts #  2 , Robert Peric  3 , Esther Oomen-de Hoop  2 , Kersten D Landa  2 , Cor H van der Leest  4 , Suzanna D Broerse  5 , Hugo B Rutten  6 , Huub N A Belderbos  4 , Christi M J Steendam  3   4 , Marthe S Paats  3 , Stijn L W Koolen  2   7 , Anne-Marie C Dingemans  3 , Teun van Gelder  7 , Roelof W F van Leeuwen  2   7 , Joachim G J V Aerts  3 , Ron H J Mathijssen  2
Affiliations
Randomized Controlled Trial

Influence of Cow's Milk and Esomeprazole on the Absorption of Erlotinib: A Randomized, Crossover Pharmacokinetic Study in Lung Cancer Patients

G D Marijn Veerman et al. Clin Pharmacokinet. 2021 Jan.

Abstract

Introduction: Erlotinib's gastrointestinal solubility and absorption are decreased by proton pump inhibitors (PPIs). Since erlotinib is a lipophilic drug, we hypothesized that concomitant intake with the fatty beverage milk may be a feasible way to increase erlotinib uptake. We performed a two-period, randomized, crossover study to investigate the influence of cow's milk with 3.9% fat on the exposure of erlotinib with and without the PPI esomeprazole in patients with non-small cell lung cancer (NSCLC). The effect of esomeprazole was studied in an additional intrapatient comparison.

Method: Pharmacokinetic sampling was performed on days 7 and 14 during 24 consecutive hours. During the 7 days prior to pharmacokinetic sampling, erlotinib was taken daily with 250 mL of either water or milk. In the PPI arm, esomeprazole (40 mg once daily 3 h prior to erlotinib) was taken for 3 days.

Results: Erlotinib area under the curve from time zero to 24 h (AUC24) did not significantly change when administered with milk, compared with water, in both non-PPI users (n = 14; - 3%; 95% confidence interval [CI] - 12 to 8%; p = 0.57) and patients who used esomeprazole (n = 15; 0%; 95% CI - 15 to 17%; p = 0.95). Esomeprazole decreased erlotinib AUC24 by 47% (n = 9; 95% CI - 57 to - 34%; p < 0.001) and Cmax by 56% (95% CI - 64 to - 46%; p < 0.001). No differences in toxicities were observed between milk and water.

Conclusion: Milk with 3.9% fat has no effect on the exposure to erlotinib in NSCLC patients, independent of PPI use. The combination with milk is safe and well tolerated. Concomitant esomeprazole treatment strongly decreased both erlotinib AUC24 and Cmax and should be avoided if possible.

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Conflict of interest statement

Christi M.J. Steendam reports grants from Roche, outside the submitted work; Anne-Marie C. Dingemans attended advisory boards and/or provided lectures for Roche, outside the submitted work (paid to institution); Teun van Gelder has received consulting fees from Roche Diagnostics, outside the submitted work; and Ron H.J. Mathijssen reports grants from Roche, outside the submitted work (paid to institution). G.D. Marijn Veerman, Koen G.A.M. Hussaarts, Robert Peric, Esther Oomen-de Hoop, Kersten D. Landa, Cor H. van der Leest, Suzanna D. Broerse, Hugo B. Rutten, Huub N.A. Belderbos, Marthe S. Paats, Stijn L.W. Koolen, Roelof W.F. van Leeuwen and Joachim G.J.V. Aerts declare no competing interests. (Part of) this work was presented at ESMO 2019 as a poster presentation (#1540P).

Figures

Fig. 1
Fig. 1
Study flowchart. After screening, patients were allocated to the non-PPI (arm A) or PPI (arm B) arms. Hereafter, they were randomized to start with administration of either concomitant water (period 1) or cow’s milk (period 2). Subsequent participation in both arms was allowed and is illustrated with the arrows between arms A and B. Hospital admissions for pharmacokinetic blood sampling took place at days 7 and 14. Esomeprazole 40 mg once daily was administered in arm B at days 5, 6 and 7, and days 12, 13 and 14. PPI proton pump inhibitor
Fig. 2
Fig. 2
Effect of cow’s milk on erlotinib concentrations. Erlotinib taken with 250 mL of cow’s milk or water, a without and b with concomitant esomeprazole administration
Fig. 3
Fig. 3
Effect of esomeprazole on erlotinib concentrations. Erlotinib taken with a 250 mL water or b cow’s milk. In the PPI arm, esomeprazole was administered 3 h prior to erlotinib intake. PPI proton pump inhibitor
See this image and copyright information in PMC

References

    1. US FDA. Erlotinib product review and label. Available at: https://www.accessdata.fda.gov/scripts/cder/daf/
    1. Planchard D, et al. Metastatic non-small cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018. 29 Suppl 4:iv192-iv237. Available at: https://www.esmo.org/Guidelines/Lung-and-Chest-Tumours/Metastatic-Non-Sm... (last updated 18 Sep 2019). - PubMed
    1. Veerman GDM, et al. Clinical implications of food-drug interactions with small-molecule kinase inhibitors. Lancet Oncol. 2020;21(5):e265–e279. doi: 10.1016/S1470-2045(20)30069-3. - DOI - PubMed
    1. Hussaarts K, et al. Clinically relevant drug interactions with multikinase inhibitors: a review. Ther Adv Med Oncol. 2019;11:1758835918818347. doi: 10.1177/1758835918818347. - DOI - PMC - PubMed
    1. Mathijssen RHJ, Sparreboom A, Verweij J. Determining the optimal dose in the development of anticancer agents. Nat Rev Clin Oncol. 2014;11(5):272–281. doi: 10.1038/nrclinonc.2014.40. - DOI - PubMed

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