24 24 CTZ 5HT 3 (), (), () () () NK1, etc
CTZchemoreceptor trigger zone ()
5HT 3
5HT 3 7, (1), (2), (1), 15HT 3,
,,,( ), CDDP, ()
(CDDP) NSCLC PS 0-2 CDDP >50mg/m2 OND 8mg DEX 4mg R (n=530) OND 8mg DEX 8mg OND 8mg DEX 12mg OND 8mg DEX 20mg MET 80mg MET 80mg MET 80mg DEX 16mg DEX 16mg DEX 8mg Total dose of DEX = 44 60mg day 1 day 2 day 3 day 4 (%) 80 60 40 20 Complete protection rate on day 1 Vomiting Nausea p<0.02 n.s. 0 4 mg 8 mg 12 mg 20 mg Italian Group for Antiemetic Research JCO 16:2937-2942, 1998
Dose effect of DEX in acute phase in a meta-analysis acute phase Total dose on day 1 Odds ratios (95%C.I.) Odds ratios (95%C.I.) Ioannidis JPA. JCO18:3409-3422, 2000 Favor control Favor DEX Favor control Favor DEX
Dose effect of DEX in delayed phase in a meta-analysis Total dose days 1-7 Odds ratios (95%C.I.) Odds ratios (95%C.I.) Ioannidis JPA. JCO18:3409-3422, 2000 Favor control Favor DEX Favor control Favor DEX
NK 1 (P) ( ) (5HT 3 RA, DEX) 1125mg, 280mg11 11130, 2 3, 5 ()
( )
11, 3 130 3( )3 ()4 (, )
25HT 3 5HT 3 40 (3) (5) 15
φ B = φ B Cp f Ki Cp f Ki+Cp f 100 5-HT 3 Ki 5-HT3 5-HT3Ki 18
100 80 555 559 p<0.001 C R 60 40 75.3 73.3 56.8 44.5 51.5 40.4 20 0 024 24120 0120 0.05 Cochran-Mantel-Haenszel test Saito.M. et al : Lancet Oncol.,10 115 (2009)
(6.6mg) 203 2,756 (0.5mg) 5.916T 3= 283 125mg 4,9461 +80mg 3,3802= 11,706 14,522
MASCC NCCN ASCO
1., 2. (, ) 3. 5HT 3 () 4. (, ) 5.,
() MASCC NCCN ASCO
1. 2. 3., (4, 3) 4., 5. 6.
(HEC: high emetogenic chemotherapeutic agents) 90% (MEC: moderate) 30~90% (LEC: low) 10~30% 10%
* オ プ シ ョ ン * *
1. HEC : Day1(iv) 2. HECMEC : Day2, No! 3. LEC5HT 3 4. HEC : HEChigh emetogenic chemotherapeutic agents MECmoderate LEClow
HEC MEC
HEC,MEC HEC MEC LEC5HT 3 HEC MEC
(2010.5.1) (day1) (day2) 5-HT 3 RA DEX8mgdays2-4 FEC, EC TS-1/CDDP DEX9.9mg APR80mgdays2-3 CPT-11/CDDP (HEC) 5FU/CDDP APR125mg CDDP APR CDDP DEX13.216.5mg (MEC) (LEC) 5-HT 3 RA DEX9.9mg (6.6mg) 5-HT 3 RA DEX4.95mg (3.3mg) APR125mg DEX6.6mg (3.3mg) DEX8mgdays2-3 APR80mgdays2-3 DEX4mg:days2-3 Non CDDP TC, CMF CPT-11 FOLFOX, FOLFIRI, XELOX, CPT-11 CBDCA CBDCA CBDCA DOC, PTX, GEM, VNR DOC, WPTX, GEM DOC, GEM, PEM PTX, DOC,, DOC, GEM 5-HT 3 RA=5-HT 3, APR=, DEX=
(HEC) (MEC) (CTCAE) (MRAT), G2
MRAT (Matsuyama Red Cross Antiemesis Tool) MAT (MASCC Antiemesis Tool) (MASCC), CTCAE CTCAE MASCC: Multinational Association of Supportive Care in Cancer
(CTCAE v4.0) Grade1 Grade2 Grade3 Grade4 241-2 243-5 246 TPN,,,, TPN,, Div,, TPN CTCAE: Common Terminology Criteria for Adverse Events
() n=14 n=46 n=54 n=126 HEC MEC
SPXPFP G228% CPT-11/CDDP G20% FEC G253%
mfolfox6 BV XELOX BV FOLFIRI BV TC (DOC/CPA) CBDCA/ PEMBV CBDCA/ CPT-11 CBDCA/ GEM G236% G230% G244% G233% G230% G231% G220%
, MEC (mfolfox6bv, FOLFIRI, XELOX/BV, TC)13 (G2 G0)7, (G2 G1)1, 5 62%
HECCDDP+AC 5-HT3 + Dex + Aprepitant Dex + Aprepitant ASCO 2011 MEC Palonosetron + Dex Dex HECCDDP+AC PALO + DEX + Aprepitant lorazepam H2RA or PPI DEX + Aprepitant lorazepam H2RA or PPI National Comprehensive Cancer Network. V1. 2012. MEC PALO + DEX Aprepitant DEX Aprepitant lorazepam H2RA or PPI lorazepam H2RA or PPI preferred Select patients: CBDCA, CPA. DXR HECCDDP 5-HT3 + Dex + Aprepitant Dex + Aprepitant ESM0/MASCC 2010 MECAC** MECnon-AC 5-HT3 + Dex + Aprepitant Palonosetron + Dex Aprepitant Dex **If Aprepitant is not available women receiving AC, PALO+DEX is recommended. 20105 HEC(CDDP+AC) MECSelect Pat MECOthers 5-HT3 + DEX + Aprepitant lorazepam H2RA or PPI 5-HT3 + DEX + Aprepitant lorazepam H2RA or PPI 5-HT3 + Dex lorazepam H2RA or PPI DEX + Aprepitant lorazepam H2RA or PPI DEX + Aprepitant lorazepam H2RA or PPI Dex lorazepam H2RA or PPI
G2 6/11 5/11 13/46 3/46 n=11 n=11 n=46 n=46 HEC(FEC) MEC
, 20%100% G2 (73%34%) FEC G2(56%)
, (20%73%), G2 (31%26%) 5HT 3 63% MEC
,,,, (,,),