Drug-Drug Interactions in Patients Treated with Anti-Cancer Agents

195 Pages·2016·6.6 MB·Dutch

Drug-Drug Interactions
in Patients Treated with
Anti-Cancer Agents
Roelof van Leeuwen
Drug-Drug Interactions in
Patients Treated with
Anti-Cancer Agents
Geneesmiddel interacties bij patiënten die behandeld
worden met antikanker geneesmiddelen
Roelof van Leeuwen
PROMOTIECOMMISSIE
Promotoren: Prof.dr. T. van Gelder
Prof.dr. A.H.J. Mathijssen
Overige leden: Prof. dr. P. Sonneveld
Prof. dr. A.J. Gelderblom
Prof. dr. J.H. Beijnen
Copromotor: Dr. F.G.A. Jansman
Colophon
ISBN: 978-90-825123-1-1
Cover design: proefschrift-aio.nl
Layout: proefschrift-aio.nl
© R. van Leeuwen, 2016
Mede mogelijk is gemaakt door Stichting de Merel, Stichting Coolsingel,
Pfizer B.V., Boehringer Ingelheim, Bayer B.V., Astra Zenica, Sanofi Aventis en
Astellas Pharma B.V.
Drug-Drug Interactions in Patients Treated with
Anti-Cancer Agents
Geneesmiddel interacties bij patiënten die behandeld
worden met antikanker geneesmiddelen
Proefschrift
ter verkrijging van de graad van doctor aan de
Erasmus Universiteit Rotterdam
op gezag van de
rector magnificus
prof.dr. H.A.P. Pols
en volgens besluit van het College voor Promoties.
De openbare verdediging zal plaatsvinden op
vrijdag 22 april 2016 om 11.30 uur
door
Roelof Wouter Frederik van Leeuwen
geboren te Maarssen
CONTENTS
Chapter 1 Introduction 6
Chapter 2 Drug-drug interactions with tyrosine kinase inhibitors:
a clinical perspective
Lancet Oncol. 2014 Jul;15(8):e315-26 20
Chapter 3 Potential drug interactions in cancer therapy: a
prevalence study using an advanced screening method
Ann Oncol. 2011 Oct;22(10):2334-41 54
Chapter 4 Potential drug-drug interactions in cancer patients
treated with oral anti-cancer drugs
Br J Cancer. 2013 Mar 19;108(5):1071-8 76
Chapter 5 Drug-drug interactions in patients treated for cancer:
a prospective study on clinical interventions
Ann Oncol. 2015 May;26(5):992-7 100
Chapter 6 Influence of the acidic beverage cola on the absorption
of erlotinib in patients with non–small-cell lung cancer
J Clin Oncol. 2016; Feb 8. Epub ahead of print 122
Chapter 7 Tyrosine kinase inhibitors and proton pump inhibitors:
really incompatible?
Submitted 140
Chapter 8 Summary 152
Appendices S amenvatting 160
Dankwoord 170
Curriculum Vitae 178
Publications 182
PhD portfolio 188
6
Chapter 1
1
GENERAL INTRODUCTION
AND AIMS OF THIS THESIS
General Introduction 7

CANCER
1
Cancer is a significant and leading public health burden and a major cause of
morbidity and mortality among men and women worldwide. Especially due
to growth, aging and adaptation of deleterious behavior and lifestyle of the
worldwide population, this burden is expected to grow in the coming years.1
Although treatment options such as cytotoxic chemotherapy, (anti)hormone
therapy and the more recent targeted agents are rapidly evolving, anticancer
treatment is still associated with many challenges. Since most anticancer
drugs have narrow therapeutic windows it is important to “get the dose right”
in order to optimize drug exposure and effect and minimalize side effects.2
To accomplish this goal there is a shifting paradigm towards individualized
dosing rather than flat-fixed dosing in order to optimize cancer therapy. Along
with other factors, such as life style, genetic factors and organ (dys)function,
the use of comedication and the subsequent risk for drug-drug-interactions
(DDIs) is one of the key factors influencing systemic drug exposure in cancer
patients (figure 1).2
Other
factors
Patient
Illness related characteristics
(i.e. performance status) (i.e. age, sex)
Body
size-measurements Exposure Genetic factors
(i.e. BSA,BMI)
Lifestyle
Co-medication
(i.e. smoking, use,
(including OTC-drugs)
food effects)
Organ function
(i.e. kidney- and
liver function)
Figure 1: Key factors influencing the systemic exposure to an anticancer drugs
Abbreviations: BMI: body-mass index; BSA: body-surface area; CAM: complementary
and alternative medicine; PPI: proton-pump inhibitor; SNPs: single-nucleotide poly-
morphisms.
General Introduction 9