1、#YT(Corresponding author), e-mail:zhang- ? 0 |s? 30 Z张晓静 张 频#SxD Sv SD S ?D = S,100021K1 化疗所致恶心、呕吐(CINV)是肿瘤患者最常见的不良反应。如果没有镇吐治疗, 70%80%接受化疗的患者会出现恶心、呕吐症状。其程度受化疗药物致吐强弱等多因素的影响。在20世纪90年代5-HT3 受体阻滞剂和地塞米松的联合应用使得70%的急性CINV得到了有效的控制。近年来开发了新一代半衰期更长、亲和力更高的5-HT3 受体阻滞剂palonosetron (帕洛诺司琼)。此外, 随着对P物质和NK-1受体研究的深入以及
2、NK-1受体阻滞剂aprepitant的问世, 急性和迟发性CINV的完全缓解率有了进一步提高。根据近年的新进展和NCCN止吐治疗指南新版本的修订, 本文综述了CINV的机制和药物治疗的研究进展。关键词 CINV s0 5-HT3 s8 F4 NK1 s8 F4中图分类号 R730.53 文献标识码 AAdvances in mechanism and treatment of chemotherapy-inducednausea and vomitingZhang Xiaojing Zhang PinCancer Hospital, CAMS h ;f h , E=f 9 90 (V ) Z
3、; BJ ;5250 mg m2; s50 mg m2;1.5g m2;,;30 90 5250 mg m2; 5s; s250mg m2; E 50 mg m2;H 9 B;H 9 D( g);9 :( g); s75mg m2;= ( g)10 30 ;100 200mg m2; UJ;8 ; x; C;G;, ?;, ?; 5 ; ;9 B;r ( g);J50250 mg m2; F; w ; w F10 ;h; E ;p ;JO50 mg m2; ; Tw;=a;=a;= _;r ;B F;d9 D; |s qs0 H sbs s u(chemoreceptor triggerzon
4、e, CTZ), Ho ?y |s w7 3 |s。 “ -v ? 31 /4Z 。v %0 ( VOT , T ,T VT _% db5-HT,5-HT3 s8 3 * . *. |s w |s 10,11 。 0# OCTZ,y |sw7 3 |s。CTZ 7K u(area pos-trema),y $ 7 p , A = VT ,|. |s w7 3 |sT。CTZO? 3Q,tOYVB“ s8 T,1 s8、F s8、a s8、 5-HT3 s8;v s019 TBs87?T。 $、 *y0Ov 7 Y , |s1。7 M YVCINVB, “5- L?CPYVNK-1 s8CINV
5、?1T,7NK1 s8 F4 V |s? 3。 “5 ksT9 L。2.2 CINV *# s8Z*# s8 |s 31T。 |s *1、F、Ya、 4, M?C5-HTP。5-HTYV5-HT3 s8s;PYVNK-1 s8s12 。2.2.1 5-HT5-HT3 s8CINVT 8=90%5-HTi _%。5-HT3 s8(M s8) *“ds *8、 *“d350 Z2006 M74 4 ONCOLOGY PROGRESS, July 2006, Vol.4, No.4$ *; w *“d“K u(area postrema) *. 8 。5-HTYV5-HT3 s8 w *“d |sQ
6、 。5-HT5-HT3 s8O. *(1 *v =# *), 3| |s w、 CTZ Y, |s313 15 。5-HT3 s8E4$CINV r .D,? |sT 。y7Cubeddu $ |s _% db5-HT , |s5-HT3 s8 F4 。7? |s5V ?i _% db5-HT., V ?i 16 。2.2.2 PNK-1 s8CINVT P 11 F *t, 3;NKA (neurokinin A、A、 *tA)NKB (neurokinin B、 *tB) tEB。P *% =s % 3iWs w *“dF 2,YV G *t s87? 3T, sY *t1s8(NK-1
7、s8)、 *t2 s8(NK-2 s8) *t3 s8(NK-3 s8)。 PNK-1 s8 T Kv,y7NK-1 s8P s8。P5-HT i _%,Ni 7 |s1 1 K u。 _%、 *、 、K u ( |s 31o, NwP V ? |s17 。P V 3 |s, “5 - kA U4P V 3 .sT。8 Pi *. 8 7 |s , P |s,NK1 s8 F4 VE% 0 |s,y74 UP V? s = 8 18 。yNPs0。NK1 s8 t s8EB(NK-1 s8、NK-2 s8、NK-3 s8)B,P T K , OPsvM19 。NK-1 s8 t 7QG s8,
8、 s8 ,?= 3IP3,9F% = 0 i, PG 0 o 0Y, 3 M。NK-1 s8E4Ti ,b 1A/ ?CP“ *(dorsalmotornucleus of the vagus nerve),y7 NK-1 s8E4T V ? )。3 s0Z3.1 5-HT3 s8E4 “5#Z5-HT3 s8E4 “ -CINVKr0, $CINVr q、 0 sz。“ - “5 5-HT3 s8E4: j(ondansetron)、 j(granisetron)、 j(tropisetron)、= j(azasetron)、 j(dolasetron)20 ,50 “51 20sT, r
9、i ?C “5ils。 v j(Palonosetron) =5-HT3 s8E4, C5-HT3 s8E4A,v40l H, s8 T 99F 30。7 j j sY4l H8l H。 “5, v j (A U A r21 。3 “5 k1 v j j j r2,22,23 , ( |s ( 24l H = |s s )1 N,Q1N 2 5? (1 5?) 。 B |s Z “5 k221 0 v j(0.25mg0.75mg)0 j(100mg) r。 569 h F, s 4 DDP (50mg m2)、CBP、CTXx = , (B? -0。 jM1, 4 F v j$? |s e
10、( j。 v j0.25mg、 0.75mg j100mg 3F$CINV qsY63%、54%52.9%,?CINVsY54%,56.6%38.7%。?CINV e v j jW As(0.25mg, P =0.004;0.75mg, P 0.001)。 h ONCOLOGY PROGRESS, July 2006, Vol.4, No.4Z2006 M74 4 351 (5.4%) H s 。6BF x “5 k1 04 v j j r 23 。 563 h F,s0 v j0.25mg0.75mg,# j32mg 3F,$CINV qsY81%、 73.5%68.6%,?CINVsY74
11、.1%、 64.6%55.1%。 v j0.25mg j32mg F$?CINV e q ( As(P0.001)。 F “5 k1 s v j0.25mg0.75mg# j32mg 3FWr2 。 667 h F。 - k , 67%h s 。“, v jF jFM1A U z q。$CINVsY:59.2%( v j0.25mg)、65.5%(0.75mg)57%( j32mg),?CINV45.3%、 48%38.9%,FW (As。 ,s ( ?z 0s, OFW Q? 3 qAs。Kn Q he(10%)L (5%)。T ( L v j Br O 0 s zB5-HT3 s8E4。s
12、 CINV , v j r j j,7 s A。3.2 NK-1 s8E4 “5Z* s8D2 , 5-HT3v -1X$ L -s0 M。2003 M S J0 S5 aprepitants Z 0、 |s,B s0NK-1 s8E4 “5 。5-HT3 s8E4, NK-1 s8E4sO WsT; O? |sTl24 。Aprepitant “ -BB “5NK-1 s8E4, x 2 sY M “5 k,sY052 (520 )054(523 ) k25,26 。 ( s DDP 70mg m2 。 ks F, aprepitantF1? j32mg, H gaprep-itant 12
13、5mg 12mg; 2 3? gaprepitant 80mg,24? g 8mg;7vF B? j32mg,H g 20mg; 2 4? g 16mg,13? gaprepitant4。1 N s5? =CINV q。 k, aprepitantr q (AvF。052 k,sY73%52% (P 0.001)25 ;054 ksY63%43%(P 0.001)26 。 kss$CINV (1?)?CINV (2 5?) q H,aprepitantF5AvF(P0.001)。Aprep-itantFvFQAs。6BF 、4v “5 k1 j (vF) j、 aprepitant (apre
14、pitantF) F ss Z HCINV r27 。866 F, 99% ( s x 0 Z。vF 1? 20mg, H g j8mg(2Q ?)aprepitant4,23? g j8mg (2Q ?)aprepitant4;aprepitantF 1? 12mg, H g j8mg (2Q ?)aprepitant125mg,2 3? gaprepitant 80mg j4。1 N 5? =CINV q。9 qaprepitantAvF,sY50.8%42.5%(P =0.015)。kss$CINV (1?) q H,aprepitantF5AvF(75.7%vs69%, P=0.034
15、),?(25?)aprepitantFvFW5As(55.4%vs 49.1%)。Fh ( 0 s z, QM 。 kT ( Ls ,S aprepitant V4CINV e q,O Q 。2006NCCN 2,、s $CINV,wiaprepi-tant、 5-HT3 30 ,?CINVwi Paprepitant 。“ -BtNK-1 s8E4“5 - “5, vofopitant (GR -205,171), CJ-11, 974, CP-122, 72128 , s352 Z2006 M74 4 ONCOLOGY PROGRESS, July 2006, Vol.4, No.4rB
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