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Τίτλος – Title
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Πνευμονική Τοξικότητα Επαγομένη από Γεμσιταμπίνη Gemcitabine induced Pulmonary Toxicity |
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Συγγραφέας – Author
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Ι. Σύριος, Ν. Τσαβαρής Ογκολογικό Ιατρείο, Κλινική Παθολογικής Φυσιολογίας, Γενικό Λαϊκό Νοσοκομείο, Ιατρική Σχολή Πανεπιστημίου Αθηνών I. Syrios, N. Tsavaris Medical Oncology Unit, Department of Pathophysiology, Laikon General Hospital, School of Medicine, Athens University, Athens, Hellas |
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Παραπομπή – Citation
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Σύριος,Ι., Τσαβαρής,Ν. : Πνευμονική Τοξικότητα Επαγομένη από Γεμσιταμπίνη, Επιθεώρηση Κλιν. Φαρμακολ. Φαρμακοκινητ. 27: 229-235 (2009) Syrios,Ι., Tsavaris,Ν. : Gemcitabine induced Pulmonary Toxicity, Epitheorese Klin. Farmakol. Farmakokinet. 27: 229-235 (2009) |
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Ημερομηνία Δημοσιευσης – Publication Date
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25 Οκτωβρίου 2009 – 2009-10-25
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Γλώσσα Πλήρους Κειμένου –
Full Text Language |
Ελληνικά – Greek |
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Παραγγελία – Αγορά –
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Ηλεκτρονική Μορφή: pdf (15 €) –
Digital Type: pdf (15 €) pharmakonpress[at]pharmakonpress[.]gr |
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Λέξεις κλειδιά – Keywords
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Γεμσιταμπίνη, πνευμονική τοξικότητα, σύνδρομο οξείας αναπνευστικής δυσχέρειας
Gemcitabine, pulmonary toxicity, acute respiratory distress syndrome
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Λοιποί Όροι – Other Terms
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Άρθρο Article |
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Περίληψη – Summary
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Η γεμσιταμπίνη είναι ένας σχετικά νέος πυριμιδινικός αντιμεταβολίτης, με συνεχώς αυξανόμενη χρήση στη θεραπεία πολλών μορφών καρκίνου. Αυτή αποτελεί ανάλογο δεσοξυκυτιδίνης (2Ά,2Ά-διφθοριοδεσοξυκυτιδίνη) με δομική ομοιότητα με την κυτοσίνη αραβινοσίδη (Ara-C), αναστέλλοντας τη σύνθεση του DNA μέσω αναστολής της DNA πολυμεράσης και της ριβονουκλεοτιδικής αναγωγάσης. Αυτή χρησιμοποιείται ευρέως σε πλειάδα συμπαγών καρκίνων, όπως του παγκρέατος, των ωοθηκών, του μαστού, της ουροδόχου κύστεως και του μη μικροκυτταρικού του πνεύμονος (NSCLC) και έχει δείξει ενθαρρυντικά αποτελέσματα σε λεμφώματα. Η γεμσιταμπίνη έχει ευνοϊκό προφίλ τοξικότητας και είναι γενικώς καλά ανεκτή. Η κυριότερη δοσοπεριοριστική τοξικότητά της είναι η μυελοκαταστολή. Σε ορισμένες μελέτες αναφέρεται πως η προκληθείσα από τη γεμσιταμπίνη πνευμονική τοξικότητα μπορεί δυνητικά να αποβεί μοιραία. Η πνευμονική τοξικότητα αφορά εμφάνιση δύσπνοιας, ενδιάμεσης πνευμονίτιδας, πνευμονικής διαταραχής, πνευμονικού οιδήματος, πνευμονικής ίνωσης, πνευμονίας, αναπνευστικής διαταραχής και συνδρόμου αναπνευστικής δυσχέρειας. Ενώ, η ήπια δύσπνοια και ο βρογχόσπασμος είναι συνήθεις επιπλοκές (10% και 2% αντίστοιχα), το σύνδρομο οξείας αναπνευστικής δυσχέρειας δεν είναι σύνηθες. Η προκληθείσα από τη γεμσιταμπίνη σοβαρή πνευμονική τοξικότητα παθοφυσιολογικά θεωρείται πως συμβαίνει μέσω φλεγμονώδους αντίδρασης των κυψελιδικών τριχοειδικών τοιχωμάτων, διαμεσολαβούμενης από κυτταροκίνες, η οποία προκαλεί ανωμαλία στη διαπερατότητα της μεμβράνης. Κλινικά παρουσιάζεται ως υποξύ σύνδρομο που χαρακτηρίζεται από λαχάνιασμα, ξηρό βήχα, κόπωση και συχνά από χαμηλή πυρετική κίνηση. Η κλασσική ακτινολογική εικόνα αφορά δικτυοοζώδεις διάμεσες διηθήσεις. Μόλις διαγνωστεί σοβαρή πνευμονική τοξικότητα, επιβάλλεται διακοπή του φαρμάκου και έναρξη χορήγησης κορτικοστεροειδών. Συστήνεται επαγρύπνηση με σκοπό την έγκαιρη διάγνωση και την κατάλληλη αντιμετώπιση των ασθενών που εμφανίζουν αυτή την τοξικότητα. Gemcitabine is a relatively new pyrimidine antimetabolite which is increasingly used for the treatment of a number of cancers. It is a deoxycytidine analog (2Ά,2Ά-difluorodeoxycytidine) with structural similarities to cytosine arabinoside (Ara-C), that inhibits DNA synthesis by inhibition of DNA polymerase and ribonucleotide reductase. It is widely used in the treatment of many solid tumors, like pancreatic, ovarian, breast, urinary bladder and non small cell lung cancer (NSCLC). Furthermore it has promising effect in lymphomas. Gemcitabine has a favorable safety profile and is generally well tolerated. The major dose-limiting toxicity is myelosuppression. Few studies report gemcitabine associated pulmonary toxicity which may be potentially fatal. Pulmonary toxicity was defined as dyspnea, interstitial pneumonitis, lung disorder, lung edema, lung fibrosis, pneumonia, respiratory disorder and respiratory distress syndrome. While mild dyspnea and bronchospasm were common (10% and 2% respectively), acute respiratory distress syndrome is rare. It is postulated that the pathophysiological mechanism of the gemcitabine induced serious pulmonary toxicity is an inflammatory reaction of the alveolar capillary wall cytokine-mediated, which creates an abnormal permeability of its membrane. The clinical presentation is a subacute clinical syndrome characterized by shortness of breath, dry cough, fatigue or malaise, and often low-grade fever. The predominant radiographic pattern on conventional chest X-ray are reticulonodular interstitial infiltrates. When serious pulmonary toxicity is diagnosed, prompt discontinuation of the drug and treatment with steroids are mandatory. There should be increased awareness in order to achieve early diagnosis and suitable management of patients developing such a toxicity. |
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Αναφορές – References
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