Dissertation committee:
Κυριακή Μυστακίδου. Καθηγήτρια, υπεύθυνη Μονάδας Ανακουφιστικής Αγωγής, Α’ Εργαστηρίου
Ακτινολογίας, Αρεταίειου Νοσοκομείου, Ιατρικής Σχολής, Εθνικού και
Καποδιστριακού Πανεπιστημίου Αθηνών (ΕΚΠΑ), Επιβλέπουσα Καθηγήτρια.
Περιστέρα Πάσχου. Αναπληρώτρια Καθηγήτρια Γενετικής Πληθυσμών, τμήματος Μοριακής Βιολογίας
και Γενετικής, Δημοκρίτειου Πανεπιστημίου Θράκης.
Βασίλειος Κουλουλίας. Αναπληρωτής Καθηγητής, Β’ Εργαστηρίου Ακττινολογίας, Μονάδας
Αντινοθεραπείας, Νοσοκομείου «Αττικόν», Ιατρικής Σχολής, Εθνικού και
Καποδιστριακού Πανεπιστημίου Αθηνών.
Αχιλλέας Χατζηιωάννου. Καθηγητής Ακτινολογίας, Α’ Εργαστηρίου Ακτινολογίας, Αρεταίειου Νοσοκομείου,
Ιατρικής Σχολής, Εθνικού και Καποδιστριακού Πανεπιστημίου Αθηνών.
Νικόλαος Αρκαδόπουλος. Καθηγητής Χειρουργικής, διευθυντής -’ Χειρουργικής Κλινικής, Νοσοκομείου
«Αττικόν», Ιατρικής Σχολής, Εθνικού και Καποδιστριακού Πανεπιστημίου Αθηνών.
Χρυσάνθη Μπατιστάκη. Επίκουρη Καθηγήτρια Αναισθησιολογίας, Β΄ Κλινικής Αναισθησιολογίας,
Νοσοκομείου «Αττικόν», Ιατρικής Σχολής, Εθνικού και Καποδιστριακού
Πανεπιστημίου Αθηνών.
Άννα Ζυγογιάννη. Επίκουρη Καθηγήτρια Ακτινοθεραπευτικής Ογκολογίας, Α’ Εργαστηρίου
Ακτινολογίας, Αρεταίειου Νοσοκομείου, Ιατρικής Σχολής, Εθνικού και
Καποδιστριακού Πανεπιστημίου Αθηνών.
Summary:
Purpose: This paper sets out to challenge thinking and practice among
researchers in the clinical and genetics field that may lead to answers on variability of
response to analgesic treatment.
Methods: This is a cohort study, performed in Greek cancer patients. Its scope
was to identify potential clinical and genetic reasons responsible for opioid change,
due to transdermal-fentanyl intolerance, resulting from inadequate analgesia (pain
relief<33% in 1week) and/or unacceptable adverse-events (grade≥3 at Common
Terminology Criteria-v4.0). The final sample included 289 participants. To investigate
responsible clinical reasons for transdermal-fentanyl intolerance its relation with
patients’ history, clinical, haematology, biochemistry, demographic and disease
related characteristics was studied. Performance status, quality-of-life and mental
state questionnaires were also used. For genetic analysis properly selected single
nucleotide polymorphisms in the genes STAT6, ARRB2, RGS4 and ADRA2A were
studied.
Results: Almost one third of the patients had to change to an alternative opioid
oral-morphine in order to achieve adequate analgesia or/and avoid adverse-events.
The most common adverse-events observed were nausea/vomiting and sleepiness.
Statistical analysis demonstrated that younger age and obesity had a higher
possibility to contribute to modification of the analgesic treatment. Furthermore, a
higher impact of symptoms in patient’s life and chemotherapy could also contribute to
the need of change of the opioid analgesic medication. Among the single nucleotide
polymorphisms analyzed, only one polymorphism in ARRB2 gene was associated
with inadequate response to analgesia with transdermal fentanyl. Furthermore,
according to the genetic statistical analysis there is a polymorphism in STAT6 gene
which puts suspicion about its relation with the need of opioid change.
Conclusion: This study found significant variables for transdermal-fentanyl
intolerance. This knowledge may help person-center care in moderate to severe
cancer pain.
This PhD was performed in the Palliative Care Unit, School of Medicine, of the
National and Kapodistrian University of Athens.
Keywords:
Genetic variation, Single nucleotide polymorphisms, Analgesia, Opioids, Fentanyl.
