повреждения сердца антрациклинами: частота и факторы риска

ÎÃËßÄ
Í.Â. Êàëèíêèíà
Äîíåöêèé ãîñóäàðñòâåííûé
ìåäèöèíñêèé óíèâåðñèòåò
Êëþ÷åâûå ñëîâà: àíòðàöèêëèíû,
êàðäèîòîêñè÷íîñòü, ÷àñòîòà,
ôàêòîðû ðèñêà.
ÏÎÂÐÅÆÄÅÍÈß ÑÅÐÄÖÀ
ÀÍÒÐÀÖÈÊËÈÍÀÌÈ:
×ÀÑÒÎÒÀ È ÔÀÊÒÎÐÛ ÐÈÑÊÀ
Ðåçþìå. Àíòðàöèêëèíîâûå àíòèáèîòèêè øèðîêî èñïîëüçóþò â êëèíè÷åñêîé ïðàêòèêå ïðè ãåìîáëàñòîçå, ëèìôîïðîëèôåðàòèâíûõ çàáîëåâàíèÿõ è
çëîêà÷åñòâåííûõ îïóõîëÿõ ðàçëè÷íîé ëîêàëèçàöèè. Îäíàêî ïðèìåíåíèå ýòèõ
ïðåïàðàòîâ îãðàíè÷åíî, ÷òî îáóñëîâëåíî ðàçâèòèåì â ïåðèîä ëå÷åíèÿ îñëîæíåíèé, íàèáîëåå îïàñíûì èç êîòîðûõ ÿâëÿåòñÿ ïîâðåæäåíèå ñåðäöà.
×àñòîòà âîçíèêíîâåíèÿ òàêèõ îñëîæíåíèé ïðè èñïîëüçîâàíèè àíòðàöèêëèíîâ ñîñòàâëÿåò îò 1,5 äî 67%. Íàèáîëåå âûðàæåííîé êàðäèîòîêñè÷íîñòüþ îáëàäàåò äîêñîðóáèöèí, îñîáåííî ïðè âûñîêîé ñêîðîñòè ââåäåíèÿ è
êóìóëÿòèâíîé äîçå 550 ìã/ì2. Çíà÷èòåëüíî ïîâûøåí ðèñê âîçíèêíîâåíèÿ
ïîâðåæäåíèÿ ñåðäöà ó äåòåé, ó áîëüíûõ â âîçðàñòå ñòàðøå 65 ëåò è ó æåíùèí. Âåðîÿòíîñòü îñëîæíåíèé âîçðàñòàåò ïðè ïðåäøåñòâîâàâøåé èëè ïàðàëëåëüíî ïðîâîäèìîé ëó÷åâîé òåðàïèè íà îáëàñòü ñðåäîñòåíèÿ, ñî÷åòàííîì ïðèåìå äðóãèõ öèòîñòàòè÷åñêèõ ñðåäñòâ è íàëè÷èè ñîïóòñòâóþùåé
ïàòîëîãèè ñåðäå÷íî-ñîñóäèñòîé ñèñòåìû.
Àíòðàöèêëèíîâûå àíòèáèîòèêè — äîêñîðóáèöèí, äàóíîðóáèöèí, ýïèðóáèöèí è äð. — øèðîêî
èñïîëüçóþò äëÿ ëå÷åíèÿ ïàöèåíòîâ ñ ãåìîáëàñòîçîì, ëèìôîïðîëèôåðàòèâíûìè çàáîëåâàíèÿìè è
çëîêà÷åñòâåííûìè îïóõîëÿìè ðàçëè÷íîé ëîêàëèçàöèè (Anderlini P. et al., 1995; Bulock F.A. et al., 1995;
Lipshultz S.E. et al., 1995; Sorensen K. et al., 1995).
Îäíàêî ïðèìåíåíèå ýòèõ ïðåïàðàòîâ îãðàíè÷åíî
âñëåäñòâèå ðàçâèâàþùèõñÿ â ïåðèîä ëå÷åíèÿ îñëîæíåíèé, èç êîòîðûõ íàèáîëåå îïàñíîå — ïîâðåæäåíèå ñåðäöà (Pihkala J. et al., 1996; Postma A. et al.,
1996). Íåðåäêî êàðäèîòîêñè÷åñêîå äåéñòâèå àíòðàöèêëèíîâ íàñòîëüêî ñåðüåçíî, ÷òî ëå÷åíèå èìè ïðåêðàùàþò äî äîñòèæåíèÿ îò÷åòëèâîãî ïðîòèâîîïóõîëåâîãî ýôôåêòà (Ëè÷èíèöåð Ì.Ð. è ñîàâò., 1994).
Ýòî îáúÿñíÿåò íåîáõîäèìîñòü èçó÷åíèÿ ðàñïðîñòðàíåííîñòè è ôàêòîðîâ ðèñêà ðàçâèòèÿ àíòðàöèêëèíîâîé êàðäèîìèîïàòèè (ÀÊ), îáóñëîâëåííîé
äåéñòâèåì àíòðàöèêëèíîâûõ ïðåïàðàòîâ.
×àñòîòà âîçíèêíîâåíèÿ êàðäèàëüíûõ îñëîæíåíèé ïðè ëå÷åíèè àíòðàöèêëèíàìè, ïî äàííûì ðàçíûõ àâòîðîâ, ñîñòàâëÿåò îò 1,5 äî 67% (òàáë. 1). Ðàñõîæäåíèå ýòîãî ïîêàçàòåëÿ, âåðîÿòíî, ñâÿçàíî ñ âîçäåéñòâèåì íåñêîëüêèõ ôàêòîðîâ. Ïî äàííûì
ëèòåðàòóðû, ðàñïðîñòðàíåííîñòü àíòðàöèêëèíîâûõ
ïîðàæåíèé ñåðäöà, ïðåæäå âñåãî, çàâèñèò îò âèäà
Òàáëèöà 1
×àñòîòà ðàçâèòèÿ êàðäèàëüíûõ îñëîæíåíèé ïðè ëå÷åíèè
àíòðàöèêëèíàìè
Àâòîðû, ãîä
Êîëè÷åñòâî áîëüíûõ ×àñòîòà, %
K. Sorensen è ñîàâòîðû, 1995
6493
1,5
F.A. Bulock è ñîàâòîðû, 1996
125
24
D. De Wolf è ñîàâòîðû, 1996
97
25
A. Postma è ñîàâòîðû, 1996
120
33
L.H. Wexler è ñîàâòîðû, 1996
23
45
L.Y. Godoy è ñîàâòîðû, 1997
31
58
J.P. Krischer è ñîàâòîðû, 1997
15
67
ïðåïàðàòà (Ãåðøàíîâè÷ Ì.Ë., 1982; Lipshultz S.E.
et al., 1995) è ðåæèìà åãî ââåäåíèÿ (Sorensen K. et al.,
1995). Ïîâûøàåòñÿ âåðîÿòíîñòü ðàçâèòèÿ êàðäèàëüíûõ îñëîæíåíèé òàêæå ïðè ïðåäøåñòâîâàâøåé èëè
ïàðàëëåëüíî ïðîâîäèìîé ëó÷åâîé òåðàïèè íà îáëàñòü ñðåäîñòåíèÿ (Kakadecar A.P. et al., 1997), ñî÷åòàííîì ïðèåìå äðóãèõ öèòîñòàòè÷åñêèõ ñðåäñòâ
(Bellamy W.T. et al., 1995; Gehl J. et al., 1996), íàëè÷èè ñîïóòñòâóþùåé ïàòîëîãèè ñåðäå÷íî-ñîñóäèñòîé ñèñòåìû (Âàëâåðå Â.Þ. è ñîàâò., 1989).  îïðåäåëåííîé ìåðå ÷àñòîòà âîçíèêíîâåíèÿ ÀÊ çàâèñèò
îò âîçðàñòà (Godoy L.Y. et al., 1997; Niitsu N. et al.,
1997) è ïîëà (Lipshultz S.E. et al., 1995) ïàöèåíòà.
Ïðåïàðàòû. Ðåçóëüòàòû àíàëèçà ëèòåðàòóðû ïîçâîëÿþò âûäåëèòü äîêñîðóáèöèí êàê ïðåïàðàò, îáëàäàþùèé íàèáîëåå âûðàæåííîé êàðäèîòîêñè÷íîñòüþ.
Ïðè÷åì â íà÷àëå åãî ïðèìåíåíèÿ èññëåäîâàòåëè îòìå÷àëè íåçíà÷èòåëüíóþ ðàñïðîñòðàíåííîñòü ïîâðåæäåíèé ñåðäöà. Òàê, ïî äàííûì êëèíè÷åñêîãî
èññëåäîâàíèÿ (Praga C. et al., 1979), ïðîâîäèìîãî
12 åâðîïåéñêèìè îíêîëîãè÷åñêèìè öåíòðàìè ñ ó÷àñòèåì 1273 ïàöèåíòîâ, ïîëó÷àâøèõ äîêñîðóáèöèí,
óñòàíîâëåíî, ÷òî íåïîñðåäñòâåííî îáóñëîâëåííîå
ïðèìåíåíèåì àíòðàöèêëèíà âîçíèêíîâåíèå êàðäèîìèîïàòèè îòìå÷åíî òîëüêî ó 1,7% èç íèõ, ïðåäïîëîæèòåëüíî îáóñëîâëåííîå — ó 3%, ïîëó÷èâøèõ
êóðñîâóþ äîçó 268 ìã/ì 2 ïîâåðõíîñòè òåëà (15–
1251 ìã/ì 2). Ëåòàëüíîñòü ñîñòàâèëà ñîîòâåòñòâåííî
0,6 è 1%.  ïîñëåäíèå ãîäû èñïîëüçîâàíèå ñîâðåìåííîé äèàãíîñòè÷åñêîé òåõíèêè (ýõîêàðäèîãðàôèè —
ÝõîÊÃ, ñòðåññ-ÝõîÊÃ, õîëòåðîâñêîãî ìîíèòîðèðîâàíèÿ, áèîïñèè ìèîêàðäà) ñïîñîáñòâîâàëî òîìó, ÷òî
ïîâðåæäåíèÿ ìèîêàðäà ïîä äåéñòâèåì àíòðàöèêëèíîâûõ ïðåïàðàòîâ ñòàëè âûÿâëÿòü ÷àùå, íà áîëåå ðàííèõ, äîêëèíè÷åñêèõ, ñòàäèÿõ è, ïî äàííûì íåêîòî-
Ó Ê Ð À ¯ Í Ñ Ü Ê È É Ì Å Ä È × Í È É × À Ñ Î Ï È Ñ – ¹ 2 (16) – III/IV 2000
25
ÎÃËßÄ
ðûõ àâòîðîâ, ïðè ïðèåìå â âûñîêèõ äîçàõ äîêñîðóáèöèíà äîñòèãàëè 67% (Wexler L.H. et al., 1996).
×àñòî äîêñîðóáèöèí èñïîëüçóþò êàê ñâîåîáðàçíûé ýòàëîí äëÿ ñðàâíåíèÿ êàðäèîòîêñè÷íîñòè äðóãèõ ïðåïàðàòîâ ãðóïïû àíòðàöèêëèíà. Òàê, ñòåïåíü
ïîâðåæäåíèÿ ñåðäöà âñëåäñòâèå ïðèìåíåíèÿ ïðåïàðàòîâ íîâîãî ïîêîëåíèÿ îöåíèâàëè â ñðàâíåíèè
ñ òàêîâîé äîêñîðóáèöèíà (=1): ïèðàðóáèöèí=0,8,
ìèòîêñàíòðîí=3,4, äàóíîðóáèöèí=0,5, àêëàðóáèöèí=0, ýïèðóáèöèí=0,6 (Okada Y. et al., 1997). Òàêèì îáðàçîì, àíòðàöèêëèíû íîâîãî ïîêîëåíèÿ (âåðîÿòíî, çà èñêëþ÷åíèåì ìèòîêñàíòðîíà) îáëàäàþò
íåçíà÷èòåëüíûì êàðäèîòîêñè÷åñêèì äåéñòâèåì.
Îäíàêî äàííûå îòíîñèòåëüíî äåéñòâèÿ ìèòîêñàíòðîíà òðåáóþò äàëüíåéøåãî óòî÷íåíèÿ, òàê êàê ðåçóëüòàòû äðóãèõ èññëåäîâàíèé (Coleman R.E. et al.,
1984) íå ïîäòâåðæäàþò åãî âûñîêîé òîêñè÷íîñòè.
Äàóíîðóáèöèí îêàçûâàë êàðäèîòîêñè÷åñêèé
ýôôåêò ó 1,5–12% ïàöèåíòîâ (Berchem G.J. et al.,
1996). Ó 17–18% áîëüíûõ, ïðèíèìàâøèõ êàðìèíîìèöèí, âîçíèêëà áîëü â îáëàñòè ñåðäöà, îòìå÷åíû
èçìåíåíèÿ íà ÝÊÃ, íî ñåðäå÷íàÿ íåäîñòàòî÷íîñòü
íå ðàçâèâàëàñü, âñå ïàöèåíòû æèâû (Ãåðøàíîâè÷ Ì.Ë., 1982). Ïîâðåæäåíèÿ ìèîêàðäà ïðè ëå÷åíèè ýïèðóáèöèíîì çàðåãèñòðèðîâàíû ó 13,3–23,1%
áîëüíûõ (Âàëâåðå Â.Þ. è ñîàâò., 1989; Venturini R.
et al., 1996).
Äîçà. ×àñòîòà ðàçâèòèÿ êàðäèàëüíûõ îñëîæíåíèé ïðè ïðèåìå àíòðàöèêëèíîâ îò÷åòëèâî êîððåëèðóåò ñ èõ êóìóëÿòèâíîé äîçîé. Ïðè îáùåé êóðñîâîé äîçå äîêñîðóáèöèíà 250–400 ìã/ì2 ïðîÿâëåíèÿ êàðäèîòîêñè÷íîñòè îáíàðóæåíû ó 1–5%
ïàöèåíòîâ, 400–500 ìã/ì 2 — ó 5–10%, ñâûøå
550 ìã/ì2 ðèñê âîçíèêíîâåíèÿ êàðäèàëüíûõ îñëîæíåíèé ðåçêî âîçðàñòàåò, äîñòèãàÿ 40% ïðè 600 ìã/ì2
(Praga C. et al., 1979) (ðèñóíîê).
×àñòîòà ðàçâèòèÿ êàðäèàëüíûõ îñëîæíåíèé, %
40
35
30
25
20
15
10
5
0
200
250
300
350
400
450
500
550
600
Êóìóëÿòèâíàÿ äîçà, ìã/ì
2
Ðèñóíîê. ×àñòîòà ðàçâèòèÿ êàðäèàëüíûõ îñëîæíåíèé ïðè ïðèåìå äîêñîðóáèöèíà â çàâèñèìîñòè îò êóìóëÿòèâíîé äîçû
26
Íåêîòîðûå èññëåäîâàòåëè îòìå÷àëè ñóáêëèíè÷åñêèå èçìåíåíèÿ êàðäèàëüíîé ôóíêöèè ïðè ïðèåìå äîêñîðóáèöèíà â äîçå 350–500 ìã/ì2 ó 58–67%
áîëüíûõ (Ëè÷èíèöåð Ì.Ð. è ñîàâò., 1994; Postma A.
et al., 1996; Wexler L.H. et al., 1996). ×àñòîòà âûðàæåííîé êàðäèîìèîïàòèè ñ ðàçâèòèåì çàñòîéíîé
ñåðäå÷íîé íåäîñòàòî÷íîñòè (ÇÑÍ) ïðè ñóììàðíûõ
äîçàõ ìåíåå 550 ìã/ì2 ñîñòàâëÿåò 0,27%, âûøå
550 ìã/ì2 — 30% (Balcerzak S.P. et al., 1978).
×àñòîòà ïîâðåæäåíèÿ ñåðäöà ïðè èñïîëüçîâàíèè
äðóãèõ àíòðàöèêëèíîâûõ àíòèáèîòèêîâ â çàâèñèìîñòè îò ñóììàðíîé äîçû íåäîñòàòî÷íî èçó÷åíà.
Èìåþùèåñÿ äàííûå ïîçâîëÿþò ñäåëàòü âûâîä î
ìåíåå âûðàæåííîé, ïî ñðàâíåíèþ ñ äîêñîðóáèöèíîì, êàðäèîòîêñè÷íîñòè ýòèõ ïðåïàðàòîâ (Coleman R.E. et al., 1984; Ðàéíîâ Þ. è ñîàâò., 1993)
(òàáë. 2). Ýïèðóáèöèí è äàóíîðóáèöèí ïðè êóìóÒàáëèöà 2
×àñòîòà ðàçâèòèÿ êàðäèàëüíûõ îñëîæíåíèé ó âçðîñëûõ
ïðè ïðèåìå àíòðàöèêëèíîâûõ àíòèáèîòèêîâ
Ïðåïàðàò
Êóìóëÿòèâíàÿ
×àñòîòà, %
äîçà, ìã/ì2
Ñóáêëèíè÷åñêèå
ÇÑÍ
èçìåíåíèÿ
Ìèòîêñàíòðîí
140
13
2,6
200
29,4
5,9
Äàóíîðóáèöèí
1,5
—
<600
1000
12
—
Ýïèðóáèöèí
13,3
—
< 600
23,1
10,6
> 1000
Èäàðóáèöèí
150
18
—
—
5
>290
Àêëàðóáèöèí
175
6
—
300
12
—
ëÿòèâíîé äîçå íèæå 600 ìã/ì2 ïðàêòè÷åñêè íå îêàçûâàåò òîêñè÷åñêîãî äåéñòâèÿ íà ñåðäöå, ïðè ïîâûøåíèè èõ äîçû âåðîÿòíîñòü êàðäèàëüíûõ îñëîæíåíèé âîçðàñòàåò (Ðàéíîâ Þ. è ñîàâò., 1993). Òàê, èç
85 ïàöèåíòîâ, ïîëó÷àâøèõ ýïèðóáèöèí â ñðåäíåé
äîçå 1000 ìã/ì2, ó 9 (10,6%) ðàçâèëàñü ÇÑÍ, 1 áîëüíîé (1,2%) óìåð îò êàðäèàëüíûõ îñëîæíåíèé
(Jensen B.V. et al., 1996). Ïðè ïðèåìå êàðìèíîìèöèíà â ñóììàðíîé äîçå 350–400 ìã/ì2 îòìå÷àëè íåçíà÷èòåëüíî âûðàæåííûå ïðîÿâëåíèÿ êàðäèîòîêñè÷íîñòè (Ãåðøàíîâè÷ Ì.Ë., 1982); èäàðóáèöèíà â
äîçå 150 ìã/ì2 — ñóáêëèíè÷åñêèå èçìåíåíèÿ ôðàêöèè âûáðîñà ëåâîãî æåëóäî÷êà (ïî äàííûì ýõîêàðäèîãðàôèè ó 18%), âûøå 290 ìã/ì2 — ðàçâèòèå êàðäèîìèîïàòèè ó 5% áîëüíûõ (Anderlini P. et al., 1995).
Ïðèìåíåíèå ìèòîêñàíòðîíà (êóìóëÿòèâíàÿ äîçà
140 ìã/ì2) îáóñëîâèëî ðàçâèòèå ÇÑÍ ó 2,6% ïàöèåíòîâ, ñóáêëèíè÷åñêèå íàðóøåíèÿ êàðäèàëüíîé ôóíêöèè — ó 13% (Recommendations for the Safe Handling
of Parenteral Antineoplastic Drugs. NIH Publication
¹ 83–2621). Ìèòîêñàíòðîí â äîçå 200 ìã/ì2 îáóñëîâëèâàë íàðóøåíèÿ ôðàêöèè âûáðîñà ëåâîãî æåëóäî÷êà ó 29,4%, ñåðäå÷íóþ íåäîñòàòî÷íîñòü — ó 5,9% áîëüíûõ (Coleman R.E. et al., 1984). Ïðè ïðèåìå àêëàðóáèöèíà (êóðñîâàÿ äîçà 175 ìã/ì2) èçìåíåíèÿ íà ÝÊÃ
íàáëþäàëè â 12%, à ïðè 175 ìã/ì2 — â 6% ñëó÷àåâ
(Åãîðîâ Ë.Å., Ðåùèêîâ Â.Ï., 1989).
Ó Ê Ð À ¯ Í Ñ Ü Ê È É Ì Å Ä È × Í È É × À Ñ Î Ï È Ñ – ¹ 2 (16) – III/ IV 2000
ÎÃËßÄ
Êóìóëÿòèâíàÿ äîçà öèòîñòàòèêà — îäèí èç îñíîâíûõ ôàêòîðîâ ðèñêà ðàçâèòèÿ ÀÊ (Lipshultz S.E.
et al., 1995; Sorensen K. et al., 1995; Pihkala J. et al.,
1996; Okada Y. et al., 1997). Òåì íå ìåíåå ðîëü ýòîãî
ôàêòîðà íå ñëåäóåò àáñîëþòèçèðîâàòü, òàê êàê íåáëàãîïðèÿòíîå âëèÿíèå äðóãèõ ôàêòîðîâ ìîæåò
îáóñëîâèòü ïîâðåæäåíèå ñåðäöà è ïðè íåâûñîêèõ
ñóììàðíûõ äîçàõ.
Ðåæèì ââåäåíèÿ. Âåðîÿòíîñòü ðàçâèòèÿ êàðäèîìèîïàòèè âîçðàñòàåò ïðè âûñîêîé ñêîðîñòè ââåäåíèÿ àíòðàöèêëèíîâ (Lipshultz S.E. et al., 1995;
Sorensen K. et al., 1995). Â ïðåäåëàõ îäíîé è òîé æå
ñóììàðíîé äîçû ââåäåíèå âûñîêèõ ðàçîâûõ äîç öèòîñòàòèêà (50 ìã/ì2 è âûøå) ïðèâîäèò ê âûñîêîé
êîíöåíòðàöèè ïðåïàðàòà â êðîâè è ïîâûøåíèþ
ðèñêà ðàçâèòèÿ è óñóãóáëåíèþ òÿæåñòè êàðäèàëüíûõ îñëîæíåíèé (Lipshultz S.E. et al., 1995; Sorensen K. et al., 1995; Krisher J.P. et al., 1997). Âåðîÿòíî,
èñêëþ÷åíèåì èç îáùåãî ïðàâèëà ÿâëÿåòñÿ ýïèðóáèöèí. Òàê, G.J. Berchem è ñîàâòîðû (1996) îáíàðóæèëè, ÷òî íåäåëüíàÿ äîçà ýòîãî ïðåïàðàòà ñâûøå
40 ìã/ì 2 íå áîëåå òîêñè÷íà, ÷åì åãî íèçøèå äîçû.
Âîçðàñò. Ó äåòåé è áîëüíûõ â âîçðàñòå ñòàðøå
65 ëåò çíà÷èòåëüíî ïîâûøåí ðèñê âîçíèêíîâåíèÿ
ïîâðåæäåíèÿ ñåðäöà ïðè ïðèåìå àíòðàöèêëèíîâ
äàæå â íåâûñîêèõ äîçàõ. ×àñòîòà ðàçâèòèÿ êàðäèàëüíûõ îñëîæíåíèé ó äåòåé, ïðèíèìàâøèõ àíòðàöèêëèíîâûå àíòèáèîòèêè, ïî äàííûì ðàçíûõ àâòîðîâ, ñîñòàâëÿåò îò 1,6 äî 45% (Hale J.P., Lewis I.J.,
1994; Sorensen K. et al., 1995; De Wolf D. et al., 1996;
Godoy L.Y. et al., 1997; Schiavetti A. et al., 1997). Â èññëåäîâàíèè J.P. Krisher è ñîàâòîðîâ (1997), ïðîâîäèâøåìñÿ ñ 1974 ïî 1990 ã. â ÑØÀ è îáúåäèíèâøåì
6493 ðåáåíêà, ïîëó÷àâøèõ àíòðàöèêëèíû ïî ïîâîäó ðàçëè÷íûõ çëîêà÷åñòâåííûõ îïóõîëåé, êàðäèîòîêñè÷íîñòü ïîäòâåðæäåíà ó 106 (1,6%) ïàöèåíòîâ:
ó 43 — âûÿâëåíû ñóáêëèíè÷åñêèå èçìåíåíèÿ êàðäèàëüíîé ôóíêöèè, ó 58 — ÇÑÍ, 5 — âíåçàïíî óìåðëè, ïðåäïîëîæèòåëüíî, îò êàðäèàëüíûõ îñëîæíåíèé. Ïðè÷åì â 89,5% ñëó÷àåâ ðàííÿÿ êàðäèîòîêñè÷íîñòü îòìå÷åíà â òå÷åíèå 1 ãîäà ïîñëå ëå÷åíèÿ.
Ïî ðåçóëüòàòàì, ïîëó÷åííûì äðóãèìè èññëåäîâàòåëÿìè (Bulock F.A. et al., 1995; Sorensen K. et al.,
1995; De Wolf D. et al., 1996; Krisher J.P. et al., 1997),
ïðåäïîëàãàåòñÿ áîëåå âûñîêàÿ ðàñïðîñòðàíåííîñòü
àíòðàöèêëèíîâûõ ïîâðåæäåíèé ñåðäöà ó äåòåé
(òàáë. 3). Ïðè÷åì ÷àùå (13–45%) îòìå÷àþò ñóáêëèÒàáëèöà 3
×àñòîòà ðàçâèòèÿ ïîâðåæäåíèé ñåðäöà ïîä âëèÿíèåì
àíòðàöèêëèíîâûõ ïðåïàðàòîâ ó äåòåé (ïî äàííûì ðàçíûõ àâòîðîâ)
Àâòîðû, ãîä
Êîëè÷åñòâî
×àñòîòà, %
áîëüíûõ Ñóáêëèíè÷åñêèå ÇÑÍ
èçìåíåíèÿ
F.A. Bulock è ñîàâòîðû, 1995
226
28
—
K. Sorensen è ñîàâòîðû, 1995
125
19
5
F.A. Bulock è ñîàâòîðû, 1996
120
28
5
J. Pihkala è ñîàâòîðû, 1996
97
25
—
D. De Wolf è ñîàâòîðû, 1996
91
32
—
L.Y. Godoy è ñîàâòîðû, 1997
23
45
—
A. Schiavetti è ñîàâòîðû, 1997
15
13
6,6
íè÷åñêèå èçìåíåíèÿ êàðäèàëüíîé ôóíêöèè, ðåæå
(5–6%) — ðàçâèòèå ÇÑÍ.
L.Y. Godoy è ñîàâòîðû (1997) ïðè èññëåäîâàíèè,
ïðîâåäåííîì ó 120 äåòåé (ñ 1985 ïî 1994 ãã.), ïðèíèìàâøèõ àíòðàöèêëèíîâûå àíòèáèîòèêè, îáíàðóæèëè ñóáêëèíè÷åñêóþ êàðäèàëüíóþ äèñôóíêöèþ ó 33
(28%) èç íèõ, ÇÑÍ — ó 6 (5%). Ðàííèå ïðîÿâëåíèÿ
êàðäèîòîêñè÷íîñòè îòìå÷àëè óæå ïðè äîçå 180 ìã/ì2.
À âñå çàðåãèñòðèðîâàííûå êàðäèàëüíûå îñëîæíåíèÿ
ðàçâèâàëèñü ïðè êóìóëÿòèâíîé äîçå 180–380 ìã/ì2,
ïðè÷åì ó äåòåé â âîçðàñòå ìëàäøå 4 ëåò ðèñê ïîáî÷íîãî äåéñòâèÿ âîçðàñòàë. F.A. Bulock è ñîàâòîðû
(1995) ïðè ïðîâåäåíèè èññëåäîâàíèÿ ñ ó÷àñòèåì
226 äåòåé, êîòîðûõ ëå÷èëè àíòðàöèêëèíàìè, ó 28%
èç íèõ âûÿâèëè ñóáêëèíè÷åñêèå íàðóøåíèÿ ôóíêöèè ñåðäöà, ïðè ýòîì ó 40% áîëüíûõ ñóììàðíàÿ äîçà
ïðåïàðàòîâ ñîñòàâèëà íèæå 400 ìã/ì2.
Ó áîëüíûõ â âîçðàñòå ñòàðøå 65 ëåò êàðäèàëüíûå
îñëîæíåíèÿ òàêæå ìîãóò âîçíèêàòü ïðè íåâûñîêèõ
(250–300 ìã/ì2) êóìóëÿòèâíûõ äîçàõ àíòðàöèêëèíîâ (Praga C. et al., 1979; Anderlini P et al., 1995; Niitsu N. et al., 1997).
Ïîë. Èìåþòñÿ äàííûå î òîì, ÷òî æåíñêèé ïîë
ÿâëÿåòñÿ îäíèì èç ôàêòîðîâ ðèñêà ðàçâèòèÿ ÀÊ
(Krisher J.P. et al., 1997). Òàê, ïðè èññëåäîâàíèè
120 ïàöèåíòîâ, ïðèíèìàâøèõ ýòè ïðåïàðàòû ïî ïîâîäó ðàçëè÷íûõ îíêîëîãè÷åñêèõ çàáîëåâàíèé, îòìå÷åíî, ÷òî ó æåíùèí ïðè áîëåå íèçêîé êóìóëÿòèâíîé äîçå ðàçâèâàþòñÿ áîëåå ÷àñòûå è òÿæåëûå
ïîâðåæäåíèÿ ñåðäöà (Lipshultz S.E. et al., 1995).
Ëó÷åâàÿ òåðàïèÿ. Ðåàëèçàöèè êàðäèîòîêñè÷åñêèõ
ýôôåêòîâ àíòðàöèêëèíîâûõ àíòèáèîòèêîâ ñïîñîáñòâóåò ïðåäøåñòâóþùåå èëè ïðîâîäèìîå îäíîâðåìåííî ñ õèìèîòåðàïèåé îáëó÷åíèå ñðåäîñòåíèÿ, ÷òî
äàåò îñíîâàíèå ìíîãèì àâòîðàì ðåêîìåíäîâàòü â
òàêèõ ñëó÷àÿõ îãðàíè÷åíèå äîçû öèòîñòàòèêîâ äî
400 ìã/ì2 (Praga C. et al., 1979; Kakadekar A.P. et al.,
1997). Òàê, íàðóøåíèÿ ñîêðàòèìîñòè ëåâîãî æåëóäî÷êà îòìå÷åíû ó 32% áîëüíûõ, ïðèíèìàâøèõ àíòðàöèêëèíû â äîçå 410 ìã/ì2, òîãäà êàê â ñî÷åòàíèè
ñ ëó÷åâîé òåðàïèåé êàðäèàëüíûå îñëîæíåíèÿ âîçíèêëè ó 50% ïðè äîçå 360 ìã/ì2 (Pihkala J. et al., 1996).
Îäíàêî èìåþòñÿ ðàáîòû, â êîòîðûõ íå îòìå÷åíî
ïîòåíöèðóþùåå äåéñòâèå ëó÷åâîé òåðàïèè íà ðàçâèòèå ïîâðåæäåíèé ñåðäöà (Kakaderkar A.P. et al.,
1997).
Êîìáèíèðîâàííàÿ õèìèîòåðàïèÿ. Âåðîÿòíîñòü
àíòðàöèêëèíîâûõ ïîâðåæäåíèé ñåðäöà âîçðàñòàåò
ïðè îäíîâðåìåííîì ïðèåìå öèêëîñïîðèíà À (Bellamy W.T. et al., 1995) è âèíêðèñòèíà (Praga C. et al.,
1979). Ñâåäåíèÿ îá àíàëîãè÷íîì äåéñòâèè öèêëîôîñôàíà íåîäíîçíà÷íû (Praga C. et al., 1979). Íåò
åäèíîãî ìíåíèÿ è ïî ïîâîäó êîìáèíèðîâàííîãî
ïðèåìà ïàêëèòàêñåëà è àíòðàöèêëèíîâ (Gianni L.
et al., 1995; Gehl J. et al., 1996; Conte P.F. et al., 1997).
Òàê, èç 30 æåíùèí, ïðèíèìàâøèõ äîêñîðóáèöèí
(ñóììàðíàÿ äîçà 369 ìã/ì 2) è ïàêëèòàêñåë ïî ïîâîäó ðàêà ìîëî÷íîé æåëåçû, ó 15 (50%) áûëè îòìå÷åíû ñóáêëèíè÷åñêèå íàðóøåíèÿ äåÿòåëüíîñòè ñåðä-
Ó Ê Ð À ¯ Í Ñ Ü Ê È É Ì Å Ä È × Í È É × À Ñ Î Ï È Ñ – ¹ 2 (16) – III/IV 2000
27
ÎÃËßÄ
öà, ó 6 (20%) — ÇÑÍ (Gehl J. et al., 1996). Ïðîòèâîïîëîæíûå ðåçóëüòàòû ïîëó÷åíû â äðóãîì èññëåäîâàíèè, â êîòîðîì êîìáèíàöèÿ ïàêëèòàêñåëà è ýïèðóáèöèíà íå òîëüêî íå ïîâûøàëà ðèñê ðàçâèòèÿ
êàðäèàëüíûõ îñëîæíåíèé, íî, íàïðîòèâ, ñíèæàëà
åãî (Conte P.E. et al., 1997).
Ñîïóòñòâóþùàÿ ïàòîëîãèÿ.  çíà÷èòåëüíîé ñòåïåíè êàðäèîòîêñè÷åñêîìó äåéñòâèþ àíòðàöèêëèíîâ ñïîñîáñòâóåò íàëè÷èå ñîïóòñòâóþùèõ çàáîëåâàíèé ñåðäå÷íî-ñîñóäèñòîé ñèñòåìû: èøåìè÷åñêàÿ
áîëåçíü ñåðäöà, ïîðîê ñåðäöà, ìèîêàðäèò, àðòåðèàëüíàÿ ãèïåðòåíçèÿ (Praga C. et al., 1979; Anderlini P.
et al., 1995; Sorensen K. et al., 1995). Òàê, ó áîëüíûõ,
ïîëó÷àâøèõ àäðèàìèöèí èëè ôàðìîðóáèöèí, ïðèçíàêè êàðäèîòîêñè÷íîñòè âîçíèêëè òîëüêî ó ïàöèåíòîâ ñ ñîïóòñòâóþùèìè ñåðäå÷íî-ñîñóäèñòûìè
çàáîëåâàíèÿìè (Âàëüâåðå Â.Þ. è ñîàâò., 1989).
Òàêèì îáðàçîì, ìîæíî îòìåòèòü, ÷òî ðèñê ðàçâèòèÿ ÀÊ íàèâûñøèé ó äåòåé è ëèö â âîçðàñòå ñòàðøå
65 ëåò, îñîáåííî ó æåíùèí, ïîëó÷àþùèõ äîêñîðóáèöèí â ñóììàðíîé äîçå âûøå 550 ìã/ì2, ïðè ðàçîâîé äîçå ïðåïàðàòà âûøå 50 ìã/ì2, ïðåäøåñòâóþùåé
èëè ïðîâîäèìîé îäíîâðåìåííî ëó÷åâîé òåðàïèè,
êîìáèíèðîâàííîé õèìèîòåðàïèè, íàëè÷èè ñîïóòñòâóþùåé ïàòîëîãèè ñåðäå÷íî-ñîñóäèñòîé ñèñòåìû.
ËÈÒÅÐÀÒÓÐÀ
Âàëâåðå Â.Þ., Øõâàöàáàÿ Ë.Â., Íþ-Òÿíü-äå Ã.Á (1989)
Ñðàâíèòåëüíàÿ îöåíêà êàðäèîòîêñè÷åñêîãî äåéñòâèÿ ïðîòèâîîïóõîëåâûõ àíòèáèîòèêîâ àäðèàìèöèíà è ôàðìîðóáèöèíà. Êàðäèîëîãèÿ, 29(9): 64–66.
Ãåðøàíîâè÷ Ì.Ë. (1982) Îñëîæíåíèÿ ïðè õèìèî- è ãîðìîíîòåðàïèè çëîêà÷åñòâåííûõ îïóõîëåé. Ìåäèöèíà, Ìîñêâà, ñ. 89–97.
Åãîðîâ Ë.Å., Ðåùèêîâ Â.Ï. (1989) Íîâûé ïðîòèâîëåéêîçíûé àíòèáèîòèê àíòðàöèêëèíîâîãî ðÿäà àêëàðóáèöèí. Ãåìàòîëîãèÿ è òðàíñôóçèîëîãèÿ, 8: 34–39.
Ëè÷èíèöåð Ì.Ð., Âûøèíñêàÿ Ã.Â., Ìèíüêîâ Å.Ä., Íàõàëîâà Ò.À., Îäæàðîâà À.À., Ãàðèí À.Ì. (1994) Ïðèìåíåíèå êàðäèîêñàíà â êà÷åñòâå êàðäèîïðîòåêòîðíîãî ñðåäñòâà ïðè ïðîòèâîîïóõîëåâîé õèìèîòåðàïèè. Òåðàïåâò. àðõ., 66(7): 54–56.
Ðàéíîâ Þ., Ãî÷åâ Ä., Ïåòðîâñêè Ï., Ãåîðãèåâ Ã.Ä. (1993)
Ñðàâíèòåëüíà îöåíêà íà êàðäèîòîêñè÷íîñòà Epirubicin â ñòàíäàðòíè è âèñîêè äîçè. Îíêîëîãèÿ, 30(Suppl.2): 23–25.
Anderlini P., Benjamin R.S., Wong F.C., Kantarjian H.M.,
Andreeff M., Kornblau S.M., Obrien S., Mackay B., Ewer M.S.,
Pierce S.A., Estey E.H. (1995) Idarubicin cardiotoxicity: A retrospective study in acute myeloid leukemia and myelodysplasia. J.
Clin. Oncol., 13: 2827–2834.
Balcerzak S.P., Christanis J., Lewis R.P. (1978) Systolic time
invervals in monitoring adriamycin induced cardiotoxicity. Cancer
Treat. Rep., 62: 893–899.
Bellamy W.T., Peng Y.M., Odeleye A., Ellsworth L., Xu M.J.,
Grogan T.M., Weistein R.S. (1995) Cardiotoxicity in the SCID
mouse following administration of doxorubicin and cyclosporin A.
Anti-cancer Drugs, 6: 736–743.
Berchem G.J., Ries F., Hanleft J., Duhem C., Keipes M.,
Delagardelle C., Dicato M. (1996) Epirubicin cardiotoxicity: a study
comparing low- with high-dose-intencity weekly schedules. Support. Care Canser, 4: 308–312.
Bulock F.A., Mott M.G., Oachill A., Martin R.P. (1995) Left
ventricular diastolic function after antracycline chemotherapy in
childhood. Relation with systolic function, symptoms and pathophysiology. Brit. Heart J., 73: 340–350.
28
Bulock F.A., Mott M.G., Oachill A., Martin R.P. (1996) Early
identefication of antracycline cardiomyopathy: possibilities and
implications. Arch. Dis. Childh., 75: 416–422.
Coleman R.E., Maisey M.N., Knight R.K., Rubens R.D. (1984)
Mitoxantrone in advanced breast cancer a phase II study with special attention to cardiotoxicity. Europ. J. Clin. Oncol., 20: 771–
776.
Conte P.F., Baldini E., Gennari A., Michelotti A., Salvadori B.,
Tibaldi C., Danesi R., Innosenti F., Gentile A., Dell’Anna R., Biadi O., Mariani L., Del Tacca L. (1997) Dose-finding study and pharmacokinetics of epirubicin and paclitaxel over 3 hours: a regimen
with high activity and low cardiotoxicity in advanced breast cancer.
J. Clin. Oncol., 15: 2510–2517.
De Wolf D., Suys B., Maurus R., Benoit Y.,Verhaaren H.,
Matthijs D., Otten J. (1996) Dobutamine stress echocardiography
in the evalution of late antracycline cardiotoxicity in chaildhood
cancer survivors. Pediat. Res., 39: 504–512.
Gehl J., Boesgaard M., Paaske T., Vittrup Jensen B., Dombernowsky P. (1996) Combined doxorubicin and paclitaxel in advanced
breast cancer: effective and cardiotoxic. Ann. Oncol., 7: 687–693.
Gianni L., Munzone E., Carpi G., Fulfaro F., Tarenzi E., Villani F., Srreafico C., Laffranchi A., Caraceni A., Martini C., Stefanelli M., Valagussa P., Bonadonna P. (1995) Paclitaxel by 3-hour
infusion in combination with bolus doxorubicin in women untreatedmetastatic breast cancer: High antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study. J. Clin. Oncol.,
13: 2688–2699.
Godoy L.Y., Fucushige J., Igarashi H., Matsuzaki A., Uega K.
(1997) Antracycline-induced cardiotoxicity in children with malignancies. Acta Pediat. Jap., 39: 188–193.
Hale J.P., Lewis I.J. (1994) Antracyclines-cardiotoxicity and
its prevention. Arch. Dis. Childh., 71: 457–462.
Jensen B.V., Nielsen S.L., Skovsgaard T. (1996) Treatment
with angiotensin-converting-enzyme inhibitor for epirubicin-induced dilated cardiomyopathy. Lancet, 347: 297–299.
Kakadecar A.P., Sandor G.G., Fryer C., Chan K.W., Rogers P.C., Pritchard S., Popov R. (1997) Differenced in dose scheduling as a factor in the etiology of antracycline-induced cardiotoxicity in Ewing sarcoma patients. Med. Pediat. Oncol., 28: 22–26.
Kimler B.F., Mansfield C.M., Sloboda D.J., Cox G.G. (1984)
Ultrastructural evidence of cardiac damage resulting from thoracic
irradiation and antracyclines in the rat. Int. J. Radiat. Oncol. Biol.
Phys., 10: 1465–1469.
Krisher J.P., Epstein S., Cuthberston D.D., Gooring A.M.,
Epstein M.L., Lipshultz S.E. (1997) Clinical cardiotoxicity following antracycline treatment for chaildhood cancer: the Pediatric
Oncology Group experience. J. Clin. Oncol., 15: 1544–1552.
Lipshultz S.E., Lipsitz S.R., Mone S.M. (1995) Female sex
and higher drug dose as risk factors for late cardiotoxic effects of
doxorubicin therapy for chaildhood cancer. New Engl. J. Med.,
332: 738–743.
Niitsu N., Kato M., Shicoshi K., Umeda M. (1997) Doxorubicin-induced myocardial damage in elderly patients with hematologic alignancies. Nippon Ronen Igakkai Zasshi, 34: 38–42.
Okada Y., Horikawa K., Sano M. (1997) Echocardiographic
evaluation of cardiotoxicity induced by antracycline therapy. Gan
To Kagaku Ryoho, 24: 585–589.
Pihkala J., Saarinen U.M., Lundstrum U., Virtanen K., Virkola K., Siimes M.A., Pesonen E. (1996) Myocardial function in children and adolescents after therapy with antracyclines and chest irradiation. Europ. J. Cancer, 32A: 97–103.
Postma A., Bink-Boelkens M.T., Beaufort-Krol G.C.,
Kengen R.A., Elzenga N.J., Schasfoort-van Leeuwen M.J.,
Kamps W.A. (1996) Late cardiotoxicity after treatment for a malignant bone tumor. Med. Pediat. Oncol., 26: 230–237.
Praga C., Beretta G., Vigo P.L., Lenaz G.R., Pollini C., Bonadonna G., Canetta R., Castellani R., Villa E., Gallagher C.G., von
Melchner H., Hayat M., Ribaud P., De Wasch G., Mattsson W.,
Heinz R., Waldner R., Kolaric K., Buehner R., Ten Bokkel-Huyn-
Ó Ê Ð À ¯ Í Ñ Ü Ê È É Ì Å Ä È × Í È É × À Ñ Î Ï È Ñ – ¹ 2 (16) – III/ IV 2000
ÎÃËßÄ
inck W., Perevodchikova N.I., Manziuk L.A., Senn H.J., Mayr A.C.
(1979) Adriamycin cardiotoxicity: a survey of 1273 patients. Cancer Treat. Rep., 63: 827–834.
Recommendations for the Safe Handling of Parenteral Antineoplastic Drugs. NIH Publication ¹83–2621. For sale the Superintendent of Documents, US Goverment Printing Office, Washington, DC 20402.
Schiavetti A., Castello M.A., Versacci P., Varasso G., Padula A., Ventriglia F., Werner B., Colloridi V. (1997) Use of ICRF187 for prevention antracycline cardiotoxicity in children: preliminary results. Pediat. Hematol. Oncol., 14: 213–222.
Sorensen K., Levitt G., Sebagmontefiore D., Bull C., Sullivan T. (1995) Cardiac function in Wilms’ tumor survivirs. J. Clin.
Oncol., 13: 1546–1556.
Venturini R., Michelotti A., Del Mastro L., Gallo L., Carnino R., Garrone O. (1996) Multicenter randomized controlled clinical trial to evaluate cardioprotection of dexrazoxane versus no cardioprotection in women receiving epirubicin chemotheraphy for
advanced breast cancer. J. Clin. Oncol., 14: 3112–3120.
Wexler L.H., Andrich M.P., Venzon D., Berg S.L., WeaverMcClure L., Chen C.C., Dilsizian V., Avila N., Jarosinski P., Balis F.M., Poplack D.G., Horovitz M.E. (1996) Randomized trial
of the cardioprotective agent ICRF-187 in pediatric sarcoma patients treated with dozorubicin. J. Clin. Oncol., 14: 362–372.
ÏÎØÊÎÄÆÅÍÍß ÑÅÐÖß
ÀÍÒÐÀÖÈÊ˲ÍÀÌÈ:
×ÀÑÒÎÒÀ ² ×ÈÍÍÈÊÈ ÐÈÇÈÊÓ
Í.Â. Êàëèíêèíà
Ðåçþìå. Àíòðàöèêë³íîâ³ àíòèá³îòèêè øèðîêî âèêîðèñòîâóþòü ó êë³íè÷í³é ïðàêòèö³ ïðè ãåìîáëàñòîç³,
ë³ìôîïðîë³ôåðàòèâíèõ çàõâîðþâàííÿõ ³ çëîÿê³ñíèõ
ïóõëèíàõ ð³çíî¿ ëîêàë³çàö³¿. Îäíàê çàñòîñóâàííÿ öèõ
ïðåïàðàò³â îáìåæåíå, ùî çóìîâëåíî ðîçâèòêîì â ïåð³îä ë³êóâàííÿ óñêëàäíåíü, íàéá³ëüø íåáåçïå÷íèì ç
ÿêèõ º ïîøêîäæåííÿ ñåðöÿ. ×àñòîòà âèíèêíåííÿ
òàêèõ óñêëàäíåíü ïðè âèêîðèñòàíí³ àíòðàöèêë³í³â
ñêëàäຠâ³ä 1,5 äî 67%. Íàéá³ëüø âèðàæåíó êàðä³îòîêñè÷í³ñòü ìຠäîêñîðóá³öèí, îñîáëèâî ïðè âèñîê³é
øâèäêîñò³ ââåäåííÿ ³ êóìóëÿòèâí³é äîç³ 550 ìã/ì2.
Çíà÷íî ï³äâèùåíèé ðèçèê âèíèêíåííÿ ïîøêîäæåííÿ
ÐÅÔÅÐÀÒÈÂÍÀ
Ðàííÿÿ äèàãíîñòèêà èøåìè÷åñêîé áîëåçíè ñåðäöà
ó áîëüíûõ õðîíè÷åñêèìè îáñòðóêòèâíûìè
çàáîëåâàíèÿìè ëåãêèõ
Ïàëååâ Í.Ð., ×åðåéñêàÿ Í.Ê., Àôîíàñüåâà È.À., Ôåäîðîâà Ñ.È. (1999). Òåð. àðõ., 71(9): 52–56.
Öåëü èññëåäîâàíèÿ — èçó÷åíèå ÷àñòîòû, îñîáåííîñòåé òå÷åíèÿ, ïðèíöèïîâ äèàãíîñòèêè è òåðàïèè
ÈÁÑ ó áîëüíûõ õðîíè÷åñêèìè îáñòðóêòèâíûìè çàáîëåâàíèÿìè ëåãêèõ (ÕÎÇË). Îáñëåäîâàëè 60 áîëüíûõ áðîíõèàëüíîé àñòìîé (ÁÀ) è õðîíè÷åñêèì îáñòðóêòèâíûì áðîíõèòîì (ÕÎÁ) ñòàðøå 40 ëåò. Ïðîâîäèëè îáùåêëèíè÷åñêèå èññëåäîâàíèÿ: çàïèñü
ÝÊÃ, ðåíòãåíîãðàôèþ îðãàíîâ ãðóäíîé êëåòêè,
ÝõîÊÃ, õîëòåðîâñêîå ìîíèòîðèðîâàíèå ÝÊÃ, ïî
ïîêàçàíèÿì — êîðîíàðîãðàôèþ. Èçó÷åíû ìàòåðèàëû àóòîïñèé 20 óìåðøèõ îò ÕÎÇË. Ïî äàííûì
àíàìíåçà, ÝÊÃ, ÝõîÊÃ, õîëòåðîâñêîãî ìîíèòîðèðî-
ñåðöÿ ó ä³òåé, ó õâîðèõ â³êîì ñòàðøå 65 ðîê³â ³ ó
æ³íîê. ³ðîã³äí³ñòü óñêëàäíåíü çðîñòຠï³ñëÿ ðàí³øå ïðîâåäåíî¿ àáî ïðè îäíî÷àñíîìó çä³éñíåíí³ ïðîìåíåâî¿ òåðàﳿ íà ä³ëÿíêó ñåðåäîñò³ííÿ, ïîºäíàíîìó ïðè çàñòîñóâàíí³ ³íøèõ öèòîñòàòè÷íèõ çàñîá³â ³
íàÿâíîñò³ ñóïóòíüî¿ ïàòîëî㳿 ñåðöåâî-ñóäèííî¿ ñèñòåìè.
Êëþ÷îâ³ ñëîâà: àíòðàöèêë³íè, êàðä³îòîêñè÷í³ñòü,
÷àñòîòà, ÷èííèêè ðèçèêó.
ANTHRACYCLINE-INDUCED HEART
DAMAGE: FREQUENCY AND RISK
FACTORS
N.V. Kalinkina
Summary. The anthracycline antibiotics are widely used
in modern clinic against various malignancies. But their
therapeutic value is limited by different complications,
one of the most dangerous of them is myocardial damage.
The frequency of the anthracycline-induced cardial
complications is from 1.5 to 67%. Doxorubicin exerts the
most intensive toxic influence on the heart. There is an
increased incidence of drug-induced cardiotoxicity at
doxorubicin cumulative doses exceeding 550 mg/m2 and
maximal doses 50 mg/m2. The risk of developing of the
cardial complications can increase in children, elderly
patients (>65 years) and women. Cardiotoxicity may
occur at lower doses in patients with prior and parallel
mediastinal irradiation, combined therapy with other
cytostatics and pre-existing heart disease.
Key words: anthracycline, cardiotoxicity, frequency,
risk factors.
Àäðåñ äëÿ ïåðåïèñêè:
Êàëèíêèíà Íàòàëüÿ Âàëåðüåâíà
86010, Ìàêååâêà, áóëüâ. 8-ãî Ñåíòÿáðÿ 4, êâ. 21
²ÍÔÎÐÌÀÖ²ß
âàíèÿ ÝÊÃ, âåëîýðãîìåòðè÷åñêîé ïðîáû, êîðîíàðîãðàôèè äèàãíîç ÈÁÑ âïåðâûå áûë óñòàíîâëåí ó
53,3% áîëüíûõ ÁÀ è ÕÎÁ. Áåçáîëåâûå ôîðìû èøåìèè ìèîêàðäà âñòðåòèëèñü â 84,4% ñëó÷àå⠗ ÷àùå,
÷åì â îáùåé ïîïóëÿöèè áîëüíûõ ÈÁÑ. Ó 70% áîëüíûõ ïðè ëå÷åíèè ïðåäóêòàëîì (òðèìåòàçèäèíîì)
îòìå÷àëîñü óìåíüøåíèå ÷àñòîòû ýïèçîäîâ áåçáîëåâîé èøåìèè ìèîêàðäà. Ìàòåðèàëû àóòîïñèé ñâèäåòåëüñòâîâàëè î âûñîêîé ðàñïðîñòðàíåííîñòè ïîðàæåíèÿ àòåðîñêëåðîçîì àîðòû è êîðîíàðíûõ àðòåðèé ó áîëüíûõ ÕÎÇË. Ñóùåñòâóþò çíà÷èòåëüíûå
òðóäíîñòè äèàãíîñòèêè ÈÁÑ ïðè ÕÎÇË, îòñóòñòâóþò ÷åòêèå êîððåëÿöèè ìåæäó êëèíè÷åñêîé êàðòèíîé ÈÁÑ è äàííûìè èíñòðóìåíòàëüíûõ èññëåäîâàíèé. Îäíèì èç ïðåïàðàòîâ âûáîðà ëå÷åíèÿ ÈÁÑ
ó áîëüíûõ ÕÎÇË ìîæåò áûòü ïðåäóêòàë.
Ó Ê Ð À ¯ Í Ñ Ü Ê È É Ì Å Ä È × Í È É × À Ñ Î Ï È Ñ – ¹ 2 (16) – III/IV 2000
29