Influence of green tea consumption on endoxifen steady-state concentration in breast cancer patients treated with tamoxifen

C Louwrens Braal,Mijntje B Vastbinder,Daniëlle Mathijssen-Van Stein,Teun Van Gelder,Stijn L W Koolen,Lieke Seuren,Esther Oomen-De Hoop,Roelof W F Van Leeuwen,Ron H J Mathijssen,Koen G A M Hussaarts,Agnes Jager,Peter De Bruijn,Monique E M M Bos,Martine F Thijs-Visser,Stefan A J Buck,Hanneke J M Zuetenhorst

doi:10.1007/s10549-020-05829-6

C Louwrens Braal, Mijntje B Vastbinder + Show 14 more

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https://doi.org/10.1007/s10549-020-05829-6

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BackgroundMany cancer patients use additional herbs or supplements in combination with their anti-cancer therapy. Green tea—active ingredient epigallocatechin-3-gallate (EGCG)—is one of the most commonly used dietary supplements among breast cancer patients. EGCG may alter the metabolism of tamoxifen. Therefore, the aim of this study was to investigate the influence of green tea supplements on the pharmacokinetics of endoxifen; the most relevant active metabolite of tamoxifen.MethodsIn this single-center, randomized cross-over trial, effects of green tea capsules on endoxifen levels were evaluated. Patients treated with tamoxifen for at least 3 months were eligible for this study. After inclusion, patients were consecutively treated with tamoxifen monotherapy for 28 days and in combination with green tea supplements (1 g twice daily; containing 300 mg EGCG) for 14 days (or vice versa). Blood samples were collected on the last day of monotherapy or combination therapy. Area under the curve (AUC0–24h), maximum concentration (Cmax) and minimum concentration (Ctrough) were obtained from individual plasma concentration–time curves.ResultsNo difference was found in geometric mean endoxifen AUC0–24h in the period with green tea versus tamoxifen monotherapy (− 0.4%; 95% CI − 8.6 to 8.5%; p = 0.92). Furthermore, no differences in Cmax (− 2.8%; − 10.6 to 5.6%; p = 0.47) nor Ctrough (1.2%; − 7.3 to 10.5%; p = 0.77) were found. Moreover, no severe toxicity was reported during the whole study period.ConclusionsThis study demonstrated the absence of a pharmacokinetic interaction between green tea supplements and tamoxifen. Therefore, the use of green tea by patients with tamoxifen does not have to be discouraged.

Highlights

Breast cancer is the most commonly diagnosed type of cancer among women [1]
The described interactions with these drugs are the result of altered bioavailability or decreased metabolism, and can mechanistically be explained by inhibition of influx transporter organic anion transporter polypeptide (OATP) or efflux transporter P-glycoprotein and several phase I and II metabolizing enzymes (e.g., cytochrome P450 (CYP) 3A and UDP-glucuronosyltransferase (UGT)) [18,19,20,21,22,23,24,25,26,27]
Estimates for the mean differences in Ctrough and Cmax were obtained for one comparison separately using a linear mixed effect model treatment with sequence, and period as fixed effects and subject within sequence as a random effect

Summary

Introduction

Breast cancer is the most commonly diagnosed type of cancer among women [1]. In the adjuvant treatment of hormone sensitive breast cancer, tamoxifen is the most frequently used. In vitro and animal studies reported a number of cancer-preventative effects of EGCG including: attenuation of oxidative stress, inhibition of angiogenesis, induction of apoptosis and alterations in expression of cell cycle regulatory proteins [11, 12, 14,15,16,17]. None of these effects have been proven clinically. The primary objective of this study was to evaluate the possible pharmacokinetic interaction between green tea supplements and tamoxifen. The secondary objective was to assess the safety profile of green tea in combination with tamoxifen

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Compliance with ethical standards