Συνδυασμός Ακτινοθεραπείας και Κυτταροπροσιασίας σε Ασθενείς με Καρκίνο Κεφαλής και Τραχήλου. Ανασκόπηση της διεθνούς Βιβλιογραφίας
Παντελής Π.1, Βαχτσεβάνος Κ.2, Κρικέλη Μ.3, Μπαρμπετάκης Ν.4, Αντωνιάδης Κ.5, Δεστούνη Ε.6
Ακτινοθεραπευτικό τμήμα Α.Ν.Θεσσαλονίκης Θεαγένειο, Κλινική Στοματικής και Γναθοπροσωπικής Χειρουργικής Α.Ν.Θ.
Θεαγένειο
Αρχεία Ελληνικής Στοματικής και Γναθοπροσωπικής Χειρουργικής 7(1): 27-37, 2006
ΠΕΡΙΛΗΨΗ
Ο πρωταρχικός στόχος της θεραπευτικής αντιμετώπισης καρκινωμάτων κεφαλής και τραχήλου είναι η επίτευξη
του τοπικού έλεγχου διατηρώντας ταυτόχρονα την ποιότητα ζωής των ασθενών.
Η πλειοψηφία των ασθενών με καρκινώματα κεφαλής και τραχήλου αντιμετωπίζονται επιτυχώς με χειρουργική
επέμβαση και ακτινοθεραπεία. Η χορήγηση ακτινοθεραπείας συνοδεύεται από την εμφάνιση οξείας
και όψιμης τοξικότητας, που μπορεί να περιορίσει την συνολική δόση της ακτινοθεραπείας, αλλά και να
επιδράσει σημαντικά στην ποιότητα ζωής των ασθενών. Σε μια προσπάθεια βελτίωσης του θεραπευτικού δείκτη
της ακτινοθεραπείας διερευνήθηκαν δύο περιπτώσεις: η χρήση ακτινοευαισθητοποιών ουσιών και η χρήση
ακτινοπροστατευτικών ουσιών.
Η πιλοκαρπίνη έχει βρεθεί αποτελεσματική στην μείωση των συμπτωμάτων που προκαλούνται από την
ακτινική ξηροστομία. Η πιλοκαρπίνη προκαλεί κένωση των εκκριτικών κοκκίων των ορωδών κυττάρων και
έτσι μειώνει την προκαλούμενη από την ακτινοβολία καταστροφή των σιελογόνων αδένων.
Η αμιφοστίνη είναι μια αποτελεσματική κυτταροπροστατευτική ουσία, η οποία προστατεύει εκλεκτικά τους
φυσιολογικούς ιστούς, ιδιαπερα τους σιελογόνους αδένες, τον βλεννογόνο της στοματικής κοιλότητας και τον
μυελό των οστών, από την κυτταροτοξική δράση της ακτινοθεραπείας και της χημειοθεραπείας.
Λέξεις κλειδιά: Ακτινοθεραπεία, τοξικότητα, ποιότητα ζωής, πιλοκαρπίνη, αμιφοστίνη, κυτταροπροστασία
REFERENCES
Abolk K, Brunk U., Jung B., Ericsson J.: Morphologic and
histochemical studies on the differing radiosensitivity ofductular
and acinar cells of the rat. Submandibular gland. VirchowsArch.
Β 45: 443-460, 1984.
AldenME., O'ReilyRC, TophamA. et al: Elapsed radiation therapy
treatment time as a predictor of survival in patients with
advanced head and neck cancer who receive chemotherapy
and radiation therapy. Radiology 201: 675-680, 1996.
Amerongen AVN., Aarsman ME., Bas-Vrengdenhil AP. et. al :
Influence of autonomic agonists on the in vitro incorporation of
[3H] leucine and N-acetyl[14C] mannosamine into
submandibular mucin of the mouse. Bioche. Biophys. Acta
798:103-110, 1984.
Antonadou D. et al : The prophylactic use of amifostine in the
prevention of chemoradiation induced mucositis and
xerostomia in head and neck cancer. Proc.Am. Soc. Ther.
Radiol. Oncol.(ASTRO) 1998.
Bachaud JM., Cohen-Jonathan E., Alzieu C. et al : Combined
postoperative radiotherapy and weekly cisplatin infusion for
locally advanced head and neck carcinoma: final report of a
randomized trial. Int. J. Radiat Oncol. Biol. Phys.36:999-1004,
1996.
Bourchis J., Fortin Α., Dupuis Ο. et al: Very accelerated radiation
therapy ; Preliminary results in locally resectable head and neck
carcinomas. Int. J. Radiat. Oncol. Biol. Phys. 32: 747-751,
1995.
Brizel DM., Wasserman TH., Henke M., Stnad V., Rudat V.,
Monnier A, Eschwege F. et. al: Phase III randomized Trial of
amifostine as a radioprotector in head and neck cancer. J. Clin.
Oncol. 18:3339-3345, 2000
Brown PE: Mechanism of action of aminothiol radioprotectors.
Nature 213:363-364, 1967
Buntzel J., Kuttner K., Frohlich D., Glatzel M: Selective
cytoprotection with amifostine in concurrent radiochemotherapy
for head and neck cancer. Ann. Oncol. 9: 505-509,
1998.
Calabro-Jones PM., Fahey RC, Smoluk GD.,Ward JF.: Alkaline
phosphatase promotes radioprotection and accumulation ofwr-
1065 in V79-171 cells incubated in medium containing WR-
2721. Int. J Radiat Oncol. Biol. Phys. 47:23-27, 1985.
Cooper JC, Faman NC, Asbel SO. et al: Recursive partitioning
analysis of 2105 patients treated in Radiation Therapy
Oncology Group Studies of head and neck cancer. Cancer 77:
1905-1911, 1996.
Denny Ρ C, Denny Ρ Α., Yim M S: The effects of various
secretagogues on the mucin content of pure submandibular
salivas. J. Dent. Res. 66.1011-1015, 1987.
Douay L, Hu C, Giarratana MC et. al : Amifostine improves the
antileukemic therapeutics index of mafosfimide : Implications
for bone marrow purging. Blood, 86:2849-2855, 1995
Dunn TA., SchnolHJ., Grunwald V. et al: Amifostine does not alter the antitumor activity of cisplatin in a pre-clinical model of
testicular cancer. Anticancer Drugs 7: 795-799, 1996.
Fichtner I., Lemm M., Becker M. et al: Effects of amifostine (WR-
2721) on tumor growth and pharmacology of cytotoxic drugs
in human xenotransplanted neuroblastomas. Anticancer Drugs
8:174-181, 1997.
Fowler JF., Lindstrom MJ.: Loss of local confrol with prolongation
in radiotherapy. Int. J. Radiat Oncol. Biol. Phys. 23: 457-467,
1992.
Gallagher J T, Hall R L, Philipps R J, Jeffery Ρ Κ, Kent Ρ W.,
Richarsson PS: Mucus glycoprotein (mucins) of the cat trachea.
Characterization and control of secretion. Bioch. Biophysic
Acta, 886:243-254, 1986.
Giatromanolaki Α., Koukourakis M., Sivridis E. et. al. Invading edge
vs inner(edvin) patients of vascularization : An interplay
between angiogenic and vascular survival factors defines clinical
behavior of non small cell lung cancer. J Path, (in press).
Glover D., Negendank W., Delivoria-Papadopoulos M., Glick JH:
Alterations in oxygen transport following WR-2721. Int. J.
Radiat. Oncol. Biol. Phys. 10:1565-1568, 1984.
Grdina DJ., Shigenatsu N., Dale P. et al : Thiol and disulfide
metavolites of the radiation protector and potential
chemopriventive agent WR-2721 are linked to both its
anticytotoxic and antimutagenic mechanisms of action.
Carcinogenesis 16: 767-774,1995.
Griffon-Etience G., Boucher Y., Brekken. C, et. al: Taxane-induced
apoptosis decompresses blood vessels an lower interstitial fluid
pressure in solid tumors: Clinical implications. Cancer Res. 59:
3776-3782, 1999.
Horiot JC, Lipinski F., Schraub S., Maylin C, Bensadoun RJ.,
Artied JM. et al: Can pilocarpine hydrochloride relieve
xerostomia regardless of the destruction of major salivary
glands?. A prospective French cooperative study. Radiother.
And Oncology (abstract) 1998.
Huang DT., Johnson CR., Schmidt-Ullrich R., Grimes M.:
Prospective radiotherapy in head and neck carcinoma with
extracapsular lymph node extension and/or positive resection
margins: a comparative study. Int. J. Radiat. Oncol. Biol. Phys.
23:737-7421992.
Johnson J.T., Ferretti G.A., Nethery W.J,Valdez I.H, Fox P.C. et
al: Oral pilocarpine for post-irradiation xerostomia in patients
with head and neack cancer. New England Journal of
Medicine329:390-395, 1993.
Kemp G, Rose P., Lurain J. et al : Amifostine pretreatment for
protection against cyclophosphamide-induced and cisplatininduced
toxicities: Results of a randomized control trial in
patients with advanced ovarian cancer. J. Clin. Oncol. 14:
2101-2112, 1996.
Kligerman MM., Tumisi AT.Ill, Urtasun RC et. al: Final report on
phase I trial of WR-2721 before protracted fractionated
radiation therapy. Int. J. Radiat. Oncol. Biol. Phys.14: 1119-
1122, 1988.
Kligerman MM., Liu T., Liu Y. et al: Interim analysis of a randomized
trial of radiation therapy of rectal cancer with/without WR-2721.
Int. J. Radiat. Oncol. Biol. Phys.22: 799-802, 1992.
Koukourakis M., Flordelis CS., Giatromanolaki A. et al : Orah
administration of recombinant human granulocytemacrophage
colony stimulating factor (rhGM-CSF) in the
management of radiotherapy iduced oesophagitis. Clin. Cancer
Res. 5:3970-3976, 1999.
Koukourakis M., Kyrias G., Kakolyris S., Kourousis Ch. et al:
Subcutaneous administration of amifostine during fractionated
radiotherapy: A randomized phase II study. J. Clin. Oncol. 18:
2226-2233, 2000.
LeVeque FG., Montgomery M., Potter D,. Zimmer M., Rieke JW.,
Steiger BW., Gallagher SC, Muscoplat CG: A multicenter
rantomized double-blind placebo-controlled dose-titration
study of oral pilocarpine for treatment of radiation induced
xerostomia in head and neck cancer patients. J. Clin. Oncol. 11:
1124-1131, 1993.
Lotz S., Cazelitz J., Tschakert H., Rephenning W., Seifert G:
Radioprotection of mini pig salivary glands by Orciprenaline-
Carbachol. Virchows Arch. A 417:119-128, 1990.
McDonald S., Meyerowitz C, Smudzin T, Rubin P: Preliminary
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Ακτινοθεραπευτικό τμήμα Α.Ν.Θεσσαλονίκης Θεαγένειο, Κλινική Στοματικής και Γναθοπροσωπικής Χειρουργικής Α.Ν.Θ.
Θεαγένειο
Αρχεία Ελληνικής Στοματικής και Γναθοπροσωπικής Χειρουργικής 7(1): 27-37, 2006
ΠΕΡΙΛΗΨΗ
Ο πρωταρχικός στόχος της θεραπευτικής αντιμετώπισης καρκινωμάτων κεφαλής και τραχήλου είναι η επίτευξη
του τοπικού έλεγχου διατηρώντας ταυτόχρονα την ποιότητα ζωής των ασθενών.
Η πλειοψηφία των ασθενών με καρκινώματα κεφαλής και τραχήλου αντιμετωπίζονται επιτυχώς με χειρουργική
επέμβαση και ακτινοθεραπεία. Η χορήγηση ακτινοθεραπείας συνοδεύεται από την εμφάνιση οξείας
και όψιμης τοξικότητας, που μπορεί να περιορίσει την συνολική δόση της ακτινοθεραπείας, αλλά και να
επιδράσει σημαντικά στην ποιότητα ζωής των ασθενών. Σε μια προσπάθεια βελτίωσης του θεραπευτικού δείκτη
της ακτινοθεραπείας διερευνήθηκαν δύο περιπτώσεις: η χρήση ακτινοευαισθητοποιών ουσιών και η χρήση
ακτινοπροστατευτικών ουσιών.
Η πιλοκαρπίνη έχει βρεθεί αποτελεσματική στην μείωση των συμπτωμάτων που προκαλούνται από την
ακτινική ξηροστομία. Η πιλοκαρπίνη προκαλεί κένωση των εκκριτικών κοκκίων των ορωδών κυττάρων και
έτσι μειώνει την προκαλούμενη από την ακτινοβολία καταστροφή των σιελογόνων αδένων.
Η αμιφοστίνη είναι μια αποτελεσματική κυτταροπροστατευτική ουσία, η οποία προστατεύει εκλεκτικά τους
φυσιολογικούς ιστούς, ιδιαπερα τους σιελογόνους αδένες, τον βλεννογόνο της στοματικής κοιλότητας και τον
μυελό των οστών, από την κυτταροτοξική δράση της ακτινοθεραπείας και της χημειοθεραπείας.
Λέξεις κλειδιά: Ακτινοθεραπεία, τοξικότητα, ποιότητα ζωής, πιλοκαρπίνη, αμιφοστίνη, κυτταροπροστασία
REFERENCES
Abolk K, Brunk U., Jung B., Ericsson J.: Morphologic and
histochemical studies on the differing radiosensitivity ofductular
and acinar cells of the rat. Submandibular gland. VirchowsArch.
Β 45: 443-460, 1984.
AldenME., O'ReilyRC, TophamA. et al: Elapsed radiation therapy
treatment time as a predictor of survival in patients with
advanced head and neck cancer who receive chemotherapy
and radiation therapy. Radiology 201: 675-680, 1996.
Amerongen AVN., Aarsman ME., Bas-Vrengdenhil AP. et. al :
Influence of autonomic agonists on the in vitro incorporation of
[3H] leucine and N-acetyl[14C] mannosamine into
submandibular mucin of the mouse. Bioche. Biophys. Acta
798:103-110, 1984.
Antonadou D. et al : The prophylactic use of amifostine in the
prevention of chemoradiation induced mucositis and
xerostomia in head and neck cancer. Proc.Am. Soc. Ther.
Radiol. Oncol.(ASTRO) 1998.
Bachaud JM., Cohen-Jonathan E., Alzieu C. et al : Combined
postoperative radiotherapy and weekly cisplatin infusion for
locally advanced head and neck carcinoma: final report of a
randomized trial. Int. J. Radiat Oncol. Biol. Phys.36:999-1004,
1996.
Bourchis J., Fortin Α., Dupuis Ο. et al: Very accelerated radiation
therapy ; Preliminary results in locally resectable head and neck
carcinomas. Int. J. Radiat. Oncol. Biol. Phys. 32: 747-751,
1995.
Brizel DM., Wasserman TH., Henke M., Stnad V., Rudat V.,
Monnier A, Eschwege F. et. al: Phase III randomized Trial of
amifostine as a radioprotector in head and neck cancer. J. Clin.
Oncol. 18:3339-3345, 2000
Brown PE: Mechanism of action of aminothiol radioprotectors.
Nature 213:363-364, 1967
Buntzel J., Kuttner K., Frohlich D., Glatzel M: Selective
cytoprotection with amifostine in concurrent radiochemotherapy
for head and neck cancer. Ann. Oncol. 9: 505-509,
1998.
Calabro-Jones PM., Fahey RC, Smoluk GD.,Ward JF.: Alkaline
phosphatase promotes radioprotection and accumulation ofwr-
1065 in V79-171 cells incubated in medium containing WR-
2721. Int. J Radiat Oncol. Biol. Phys. 47:23-27, 1985.
Cooper JC, Faman NC, Asbel SO. et al: Recursive partitioning
analysis of 2105 patients treated in Radiation Therapy
Oncology Group Studies of head and neck cancer. Cancer 77:
1905-1911, 1996.
Denny Ρ C, Denny Ρ Α., Yim M S: The effects of various
secretagogues on the mucin content of pure submandibular
salivas. J. Dent. Res. 66.1011-1015, 1987.
Douay L, Hu C, Giarratana MC et. al : Amifostine improves the
antileukemic therapeutics index of mafosfimide : Implications
for bone marrow purging. Blood, 86:2849-2855, 1995
Dunn TA., SchnolHJ., Grunwald V. et al: Amifostine does not alter the antitumor activity of cisplatin in a pre-clinical model of
testicular cancer. Anticancer Drugs 7: 795-799, 1996.
Fichtner I., Lemm M., Becker M. et al: Effects of amifostine (WR-
2721) on tumor growth and pharmacology of cytotoxic drugs
in human xenotransplanted neuroblastomas. Anticancer Drugs
8:174-181, 1997.
Fowler JF., Lindstrom MJ.: Loss of local confrol with prolongation
in radiotherapy. Int. J. Radiat Oncol. Biol. Phys. 23: 457-467,
1992.
Gallagher J T, Hall R L, Philipps R J, Jeffery Ρ Κ, Kent Ρ W.,
Richarsson PS: Mucus glycoprotein (mucins) of the cat trachea.
Characterization and control of secretion. Bioch. Biophysic
Acta, 886:243-254, 1986.
Giatromanolaki Α., Koukourakis M., Sivridis E. et. al. Invading edge
vs inner(edvin) patients of vascularization : An interplay
between angiogenic and vascular survival factors defines clinical
behavior of non small cell lung cancer. J Path, (in press).
Glover D., Negendank W., Delivoria-Papadopoulos M., Glick JH:
Alterations in oxygen transport following WR-2721. Int. J.
Radiat. Oncol. Biol. Phys. 10:1565-1568, 1984.
Grdina DJ., Shigenatsu N., Dale P. et al : Thiol and disulfide
metavolites of the radiation protector and potential
chemopriventive agent WR-2721 are linked to both its
anticytotoxic and antimutagenic mechanisms of action.
Carcinogenesis 16: 767-774,1995.
Griffon-Etience G., Boucher Y., Brekken. C, et. al: Taxane-induced
apoptosis decompresses blood vessels an lower interstitial fluid
pressure in solid tumors: Clinical implications. Cancer Res. 59:
3776-3782, 1999.
Horiot JC, Lipinski F., Schraub S., Maylin C, Bensadoun RJ.,
Artied JM. et al: Can pilocarpine hydrochloride relieve
xerostomia regardless of the destruction of major salivary
glands?. A prospective French cooperative study. Radiother.
And Oncology (abstract) 1998.
Huang DT., Johnson CR., Schmidt-Ullrich R., Grimes M.:
Prospective radiotherapy in head and neck carcinoma with
extracapsular lymph node extension and/or positive resection
margins: a comparative study. Int. J. Radiat. Oncol. Biol. Phys.
23:737-7421992.
Johnson J.T., Ferretti G.A., Nethery W.J,Valdez I.H, Fox P.C. et
al: Oral pilocarpine for post-irradiation xerostomia in patients
with head and neack cancer. New England Journal of
Medicine329:390-395, 1993.
Kemp G, Rose P., Lurain J. et al : Amifostine pretreatment for
protection against cyclophosphamide-induced and cisplatininduced
toxicities: Results of a randomized control trial in
patients with advanced ovarian cancer. J. Clin. Oncol. 14:
2101-2112, 1996.
Kligerman MM., Tumisi AT.Ill, Urtasun RC et. al: Final report on
phase I trial of WR-2721 before protracted fractionated
radiation therapy. Int. J. Radiat. Oncol. Biol. Phys.14: 1119-
1122, 1988.
Kligerman MM., Liu T., Liu Y. et al: Interim analysis of a randomized
trial of radiation therapy of rectal cancer with/without WR-2721.
Int. J. Radiat. Oncol. Biol. Phys.22: 799-802, 1992.
Koukourakis M., Flordelis CS., Giatromanolaki A. et al : Orah
administration of recombinant human granulocytemacrophage
colony stimulating factor (rhGM-CSF) in the
management of radiotherapy iduced oesophagitis. Clin. Cancer
Res. 5:3970-3976, 1999.
Koukourakis M., Kyrias G., Kakolyris S., Kourousis Ch. et al:
Subcutaneous administration of amifostine during fractionated
radiotherapy: A randomized phase II study. J. Clin. Oncol. 18:
2226-2233, 2000.
LeVeque FG., Montgomery M., Potter D,. Zimmer M., Rieke JW.,
Steiger BW., Gallagher SC, Muscoplat CG: A multicenter
rantomized double-blind placebo-controlled dose-titration
study of oral pilocarpine for treatment of radiation induced
xerostomia in head and neck cancer patients. J. Clin. Oncol. 11:
1124-1131, 1993.
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