Judith K. Wolf, MD Professor

1
??????21?????
Judith K. Wolf Professor Gynecologic Oncology

• Judith K. Wolf, MDProfessor Department of
  Gynecologic Oncology University of Texas M.D.
  Anderson Cancer Center Houston, TX

2
??? 2010?

• ??????????1/71 1
• 5????(??????)2
• 1990-1992 42.5
• 1993-1995 43.5
• 1996-2003 45
• ???????????,?5??????????????

1. SEER (Surveillance, Epidemiology, and End
Results) Program Web site. http//seer.cancer.
gov/statfacts/html/ovary.html. Accessed April 22,
2007. 2. http//seer.cancer.gov/csr/1975_2004/resu
lts_merged/sect_21_ovary.pdf. Accessed April 22,
2007.
3
?????

• I? ?????
• A. ????
• B. ????
• C. ?????
• II? - ?????
• A. ?????????
• B. ??????
• C. ?????
• III? ??????????????
• A. ??????
• B. ????????? lt 2 cm
• C. ????????? gt 2 cm
• IV ? ???????, ????????

4
??? FIGO ????

• ?? ?? ??? ???
• I ????? 20 73
• II ????? 5 45
• III ?????/??? 58 21
• IV ???? 17 lt5

Jelic S, et al. Program and abstracts of the 27th
Congress of the European Society for Medical
Oncology 2002 Nice, France. Mocharnuk R.
Medscape Web site. http//www.medscape.com/viewart
icle/444134. Accessed May 2, 2007.
FIGO ???????
5
???????????
????
?? (??)
???/?????

• ?? (??????)
• ??????
• ???????

????/ ?? (??)
TAH ?????? BSO ?????????
6
???? ??????
??????????? ???????lt1cm
?? ??????(?? ???)
7
??

• ??????????????, AUC 6 ? 7.5, ??? 175 mg/m2
  ,?21???,??6??
• ????????????
• GOG 1111 ? OV 102?? ???/?? vs ????/??
• GOG 1583 ? AGO OVAR-34?? ??????

1. McGuire WP, et al. N Engl J Med.
1996334(1)1-6.2. Piccart MJ, et al. J Natl
Cancer Inst. 200092(9)699-708. 3. Ozols RF, et
al. J Clin Oncol. 200321(17)3194-3200.4. du
Bois AD, et al. J Natl Cancer Inst.
200395(17)1320-1329.
GOG Gynecologic Oncology GroupAGO
ArbeitsgemeinschaftGynaekologische Onkologie
8
???????????????
?? ???? ?? ?? PFS (?) ?? OS (?)
GOG 1321 377? III ???????,?IV??? ??/??? (24 ??) x 6 14.1 26.3
GOG 1321 377? III ???????,?IV??? ?? 100 mg/m2 x 6 16.4 30.2
GOG 1321 377? III ???????,?IV??? ??? 200 mg/m2 (24 ??) 10.8 25.9
ICON32 2074? I-IV??? ??/ ??? (3 ??) 17.3 36.1
ICON32 2074? I-IV??? ?? ? CAP 16.1 35.4
CAP ????, ???, ??GOG ????? ICON
????????OS ????? PFS ???????
??????/????????(42) vs ?? (67), P lt.001
1. Muggia FM, et al. J Clin Oncol.
200018(1)106-115. 2. International
Collaborative Ovarian Neoplasm Group. Lancet.
2002360(9332)505-515.
9
???????????????
?? ???? ?? ?? PFS (?) ?? OS (?)
GOG 1581 792? III ????????? ?? 75 mg/m2??? 135 mg/m2 (24 h) 19.4 48.8
GOG 1581 792? III ????????? ?? AUC 7.5??? 175 mg/m2 (3 h) 20.7 56.7
GOG 1581 792? III ????????? ??????????? 0.88 (95 CI) ??????????? 0.86 (95 CI) HR 0.86 (99 CI)
AGO2 798? IIB-IV??? ?? 75 mg/m2??? 185 mg/m2 (24 h) 19.1 44.1
AGO2 798? IIB-IV??? ??AUC 6???185 mg/m2 (3 h) 17.2 43.3
AGO2 798? IIB-IV??? HR 1.050 (95 CI) HR 1.045 (95 CI)
????????????? ????????????? ????????????? ????????????? ?????????????
AGO Arbeitsgemeinschaft Gynaekologische
OnkologieCI ????GOG ?????HR ??? OS
????? PFS ???????RR ?????
1. Bookman MA, et al. Int J Gynecol Cancer.
200313(s2)149155. 2. du Bois AD, et al. J
Natl Cancer Inst. 200395(17)1320-1329.
10
SCOTROC ????
???????
?? AUC 5, ???? 75 mg/m2 (1 h)?3??? x 6 ??
AUC 5, ???175 mg/m2 (3 h)?3??? x 6

• Ic-IV????
• ??????
• N 1077

SCOTROC ????????????Q3W ?3???
Vasey PA, et al. J Natl Cancer Inst.
200496(22)1682-1691.
11
SCOTROC ????

• ?? ????-?? ???-??
• ??? (??) 59 60
• ??? (CA-125) 76 77
• ??????? 15? 14.8?
• 24???????? 64 69

DC ????-??PC ???-??SCOTROC ????????????
Vasey PA, et al. J Natl Cancer Inst.
200496(22)1682-1691.
12
SCOTROC ??

• PC vs DC PC ??????
• ?????????/???,???????????????
• ???????????????????????
• ?????????????,??????????????
• ???????,????????,???/?? ??????????????

DC ????-?? PC ???-??
Vasey PA, et al. J Natl Cancer Inst.
200496(22)1682-1691.
13
GOG 182-ICON5 III/IV?????????
?? I (???l) ??? 175 mg/m2 IV (3 h) d 1 ?? AUC 6
IV d 1
?? II (?? A) ??? 135 mg/m2 IV (3 h) d 1 ?? AUC
5 IV d 1 ???? 800 mg/m2/d IV d 1, 8
??I, II, III 8 ??, ??21? ?? IV ? V 4 ??, ??21?

• ???
• ????
• ???????????
• ?????? ???????, ?????, ???

?? III (?? B) ??? 135 mg/m2 IV (3 h) d 1 ?? AUC
5 IV d 1 ??????30 mg/m2 IV d 1 ??????
?? IV (???? A) ?? AUC 5 IV d 3 ???? 1.25 mg/m2/d
IV d 1-3
?? IV (???? B) ??? 175 mg/m2 IV (3 h) d 1 ??
AUC 6 IV d 1
?? V (???? A) ?? AUC 6 IV d 8 ???? 1000 mg/m2/d
IV d 1, 8
?? V (???? B) ??? 175 mg/m2 IV (3 h) d 1 ?? AUC 6
IV d 1
GOG ????? ICON ???????? OS ????? PFS
??????? RR ???
Bookman MA. J Clin Oncol. 200624(18S)Abstract
5002.
14
GOG0182-ICON5 ???????
????
??????????
Median PFS and HR (95 CI) 16.1 1.000 16.4
0.990 (0.884-1.107) 16.4 0.998
(0.891-1.117) 15.3 1.094
(0.979-1.224) 15.4 1.052 (0.940-1.176)
?????????(?)
C ?? D ?????? G ???? P ??? PFS
???????T ????
Bookman MA. J Clin Oncol. 200624(18S)Abstract
5002.
15
GOG0182-ICON5 ?????
???????
Median OS and HR (95 CI) 40.0 1.000 40.4
0.978 (0.838-1.141) 42.8 0.972
(0.832-1.136) 39.1 1.068
(0.918-1.244) 40.2 1.035 (0.888-1.206)
?????????(?)
C ??D ??????G ????P ??? 0S ?????T
????
Bookman MA. J Clin Oncol. 200624(18S)Abstract
5002.
16
GOG????????????
GOG 218
gt ??????? ?????????????
??? ?? ???
??? ?? ????
??? ?? ????
???? 16 ??
??? 16 ??
??? 16 ??
EOC ??????FT ??? GOG ?????PFS
??????? PPC ?????? QOL ????
N 2,000 ??? ?????????????????? ??????????????
17
EORTC-55971
IIIc?IV??????? ??????? vs ?????
?????
3 ??????????
3 ??????????
????????????????? ???????
?????? ???????
????? ???
????? ???
EORTC ??????????? IDS ?????????? SLS ???
The EORTC Groups Web site. Gynaecological Cancer
Group Active Study Protocols. http//groups.eortc.
be/gcg/studyprotocols.htm55971. Accessed June
12, 2007.
18
GC vs TC ???????????? ????
?????????????IC-IV???????,????????????
GC?????? ???? 1000 mg/m2 Days 1, 8 ?? AUC 5
Day 1 x 6 ??,?21???
TC?????? ??? 175 mg/m2 Day 1 ?? AUC 6 Day 1 x 6
??,?21???
??????
???????? ????? (PR, SD, PD)
???????? ????? (PR, SD, PD)
????????? ??? 135 mg/m2 ?28???,?12??
???? ??? 175 mg/m2 Day 1
???? ???? 1000 mg/m2 Days 1, 8
Gordon A, et al. ASCO 2008. Abstract 5536.
19
GC vs TC ???????????? ???
?????, n () GC???? (n 66) TC???? (n 58) P ?
???? 30 (45.5) 26 (44.8)
???? 13 (19.7) 12 (20.7)
???? 5 (7.6) 8 (13.8)
???? 6 (9.1) 4 (6.9)
????? 12 (18.2) 8 (13.8)
???? (???? ????) 43 (65.2) 38 (65.5) ? .999
????? (???? ????????) 48 (72.7) 46 (79.3) .410
???? ?? CA-125??????.
Gordon A, et al. ASCO 2008. Abstract 5536.
20
GC vs TC ???????????? ?????????
????, n () GC???? (n 219) TC???? (n 220) P ?
?????
G3/4 ????? 88 (40.2) 55 (25.1) 30 (13.6) 10 (4.5) ? .0001
G3/4 ?? 52 (23.7) 20 (9.1) ? .0001
??????
? G2 ?????? 24 (11.0) 43 (19.5) .0165
G2 ?? 79 (36.1) 110 (50.0) .0038
????? 7 (3.2) 0 (0) .0073
Gordon A, et al. ASCO 2008. Abstract 5536.
21
??vs????? TC?? (??) ????
II-IV???????, ???????????
???????? ??????? 1 cm vs gt 1 cm FIGO?? II ?
vs III? vs IV?????? ?????/??? vs ???/????
??TC??(c-TC) ??? 180 mg/m2 Day 1 ?? AUC 6.0 Day
1 ?21???? 6-9 ??
????? TC???? (dd-TC) ???80 mg/m2 Days 1, 8, 15
?? AUC 6.0 Day 1 ?21???? 6-9 ??
Isonishi S, et al. ASCO 2008. Abstract 5506.
22
??vs????? TC?? (??)????
?? ???, ???,
?? ??TC?? (n 135) ????TC?? (n 147)
????? 53 56
????? 16 20
????? 38 36
??? 31 29
???? 7 3
???? 9 12
P .72
Isonishi S, et al. ASCO 2008. Abstract 5506.
Evaluated by WHO criteria
23
??vs????? TC?? (??) ???????
Isonishi S, et al. ASCO 2008. Abstract 5506.
1.0
0.9
?????TC
0.8
??TC
0.7
0.6
??????????
0.5
0.4
0.3
0.2
0.1
0.0
0
12
30
54
6
18
42
24
48
36
?????????(?)
?? n ?? ??PFS, ? P ? HR 95 CI
??TC 319 200 17.2
????TC 312 160 28.0 .0015 0.714 0.581-0.879
24
???????
?????????
??????????
???
??
??
??
?? 2
??
?? 1
?? 3
??/ ??
??
????
?? ?????????
25
??????????

• ??????
• ????????
• ????????
• ?????????????
• ?????????

26
?????????????

• ?????
• ??/???????
• ?????????
• ????????
• ?????????
• ???????????
• ??????
• ????
• ????????
• ??/?????
• ????

27
????????????

• ????
• ????
• ??????
• CA-125
• ???
• CT ??
• MRI?
• PET ???

CT computed tomography MRI magnetic resonance
imaging PET positron emission tomography
28
??? ?????

• CA-125?????
• CA-125 ?? 100
• ?????
• ???????
• ????
• ????

29
????????
???? ?? ?? ?????
???????III? GOG 114 IV ?? ???, IP ?? 28 ?
GOG 172 IV ???, IP ?? ??? 24 ?
GOG 158 IV ??? ?? 21 ?
GOG 114 IV ??? ?? 22 ?
GOG 158 IV ??? ?? 19 ?
GOG 172 IV ??? ?? 18 ?
??????III/IV? GOG 111 IV ??? ?? 18 ?
GOG 162 IV ??? ?? 12 ?
GOG 152 IV ??? ?? 11 ?
IC-IV? SCOTROC ???? ?? 15 ?
IC-IV? SCOTROC ??? ?? 15 ?
?? III IV? GOG 182 IV ???/?? x 8 16 ?
Carb carboplatin Cis cisplatin Doc
docetaxel pac paclitaxelGOG Gynecologic
Oncology Group IP intraperitoneal Pac
paclitaxel
30
?????????
FDA ?? FDA ?? FDA ??
???? ?? ??
????/ ?? ??? ??????
????
?FDA ??, ???? ?FDA ??, ???? ?FDA ??, ????
????? ???? ????
??? ???? ????
5-FU/LV ???? ?????
???? ??? ????
??? ????
?FDA ??, ????? ?FDA ??, ????? ?FDA ??, ?????
???? ???? ????
????
31
????????????
?????

15
20
30
30

???????????() ???????????() ???????????()
???? (?) Markman Gore Blackledge
0-6 17 10
7-12 27 17 29
13-18 33 27 63
19-24 33 27 94
gt24 59 57
Markman M, et al. J Clin Oncol.
19919(3)389-393. Gore ME, et al. Gynecol
Oncol. 199036207-211. Blackledge G, et al. Br J
Cancer. 198959650-653.
32
?????????????
0 3 6 12 18 24
? ? ? ?
?
????
????
????
????
???????????, ???? (CA-125)??
33
ICON 4 ??
?????????
?????

• ????????
• ????????
• ???????????

?????????

• ????
• ?? (31)
• ???/?? (40)
• ?? (30)
• 75???????? gt 12 ??

ICON International Collaborative Ovarian
Neoplasm Group TFI treatment-free interval
Parmar MK, et al. Lancet. 20033612099-2106.
34
ICON 4 ???
(???12 95 CI -0.1 - 24 p0.06)
CR ???? ICON ???????? Pac ??? Plat ??
PR ????
Parmar MK, et al. Lancet. 20033612099-2106.
35
??? ICON 4 ???????
1.0

Hazard ratio 0.76 (95 CI 0.66 - 0.89 p lt
0.001)
0.9
0.8
0.7
1??????? 10 (40 to 50 95 CI 4 to 15)
0.6
??????????
0.5
0.4
0.3
0.2
0.1
0.0
0
1
2
3
4
?????????????(?)
??????
???-??
392 179 52
25 17
??
410 157 45
17 7
ICON ???????? Pac ??? Plat ??
Parmar MK, et al. Lancet. 20033612099-2106.
36
ICON 4 ?????
Hazard ratio 0.82 (95 CI 0.69 - 0.97 p
0.023)
1.0
0.9

2??????? 7 (50 to 57 95 CI 1 to 12)
0.8
0.7
???????
0.6
0.5
0.4
0.3
0.2
0.1
0.0
0
1
2
3
4
?????????????(?)
??????
???-??
392 306 167
96 43
??
410 295 150
68 33
ICON International Collaborative Ovarian
Neoplasm Group Pac paclitaxel Plat platinum
Parmar MK, et al. Lancet. 20033612099-2106.
37
????/?? vs ?? ????

• ??????
• ???????6????
• ??
• ????? (6-12,gt12??)
• ???? (?? ???)
• ??? vs ???
• ?????? PFS

???? 1,000 mg/m2 days 1 8 Plus ?? AUC 4
day 1
? ? ? ??
?21??? 6 ??
?? AUC 5 day 1
?21??? 6 ??
Carbo ?? Gem ???? PFI ????? PFS ???????
Pfisterer J, et al. J Clin Oncol. 2006
244699-4707.
38
AGO OVAR 2.5 ?????? ???????
Log-rank ??P? 0.0038 ??? HR 0.72 (0.57 to
0.90) ???? HR 0.71 (0.57 to 0.89)
???? ?? 8.6 ?? ?? 12.4
????? (N178)
??? (N178)
?? ?? 5.8 ???? 12.9
????????????????
AGO Arbeitsgemeinschaft Gynaekologische
Onkologie GCb ???? Cb ??
Pfisterer J, et al. J Clin Oncol.
2006244699-4707.
39
AGO OVAR 2.5 ????? ?????
1.0
0.9
?? 18.0 ?? ?? 18.5
????? (N178)
0.8
??? (N178)
0.7
???????
0.6
Log-rank p-value 0.7349 ??? HR 0.96 (0.75 to
1.23) ??? HR 0.92 (0.72 to 1.16)
0.5
0.4
?? 17.3 mo ?? 22.5
0.3
0.2
0.1
0.0
0
6
12
18
60
54
48
42
36
30
24
?
AGO Arbeitsgemeinschaft Gynaekologische
Onkologie GCb ???? Cb ??
???????????????????????
Pfisterer J, et al. J Clin Oncol.
2006244699-4707.
40
GCIG CALYPSO ????
??????? (???? 864???)??????????????
?????? 30 mg/m2 ?? AUC 5 q 28 days x 6
? ? ? ?
????? ?????? lt 0.5 cm gt 0.5-2 cm
??? 175 mg/m2 ?? AUC 5 q 21 days x 6
GCIG Gynecologic Cancer Intergroup PFS
??????? PLD ??????
41
Farletuzumab (MORAb-003)??????????????? ????

• FRA ??????????????? ????????????
• MORAb-003?FRA??????Lyn??????????
  ???FRA??????????? ?????????????????????????
• MORAb-003??? I ???????????????,??????????????????

42
MORAb-003 ??????????? II???????

• ???????????
• 6-18 ???????????CA125 ?????
• (??58? ??????54?)

????????
????????
??? ??/??? ???? Farletuzumab ? 6 ?? (n 26)
???? Farletuzumab ??????(n 28)
?? ORR
???? ORR
?????Farletuzumab ??
????????????????
Armstrong DK, et al. ASCO 2008. Abstract 5500.
43
MORAb-003-002 II??? ???

• ???
• MORAb-003 100 mg/m2 ??
• ??? ?6 ???? ??37.5 mg/m2 ? ?6???? ??62.5 mg/m2
• ?????? 21??? x 6 ??
• ?? AUC 5-6
• ???
• ??? 175 mg/m2 ? 3 ?? ?
• ???? 75 mg/m2

Armstrong DK, et al. ASCO 2008. Abstract 5500.
44
???????????? n 6
??? ????, ? ????, ? ??
1 8.3 19.5 ??????
2 10.8 19.1 ??????
3 10.1 15.8 ??????
4 9.5 9.6 ??????
5 8.2 8.2 ??
6 6.5 7.8 ??????
Data as of May 5, 2008.
Armstrong DK, et al. ASCO 2008. Abstract 5500.
45
??RECIST?? MORAb-003-002 ?????? (????)

• ?????
• ???? 7.4
• ???? 62.9
• ???? 25.9
• ???? 3.7
• ????2007?12?3?????????? ( 30)
• ????????????????
• MORAb-003 ????? ????????????

???? 70.3
???? 96.3
Armstrong DK, et al. ASCO 2008. Abstract 5500.
46
?????????

• ???
• ?????
• ????????????????????????????
• ?????gt12?
• ??????
• ?? ????

PFI ?????
47
???????????? ????
?? Janicke Segna Zang Gadducci Eisenkop Munkarah
Scarabelli Tay ??/??
?? 1992 1993 2000 2000 2000 2001 2001 2002
?? 30 100 60 30 114 25 148 46 553
?????? ? 16 16.6 13 21 16.8 26 13-26
???? ? lt12 lt12 lt12 lt17.5 lt12 lt24 lt12 lt12
?????? ? 8 8.8 8 15 25 42 12 6 6-42
?????? ? (P) 29 (0.002) 22.9 (0.007) 12 (0.02) 25
(0.04) 56.8 (0.005) 57 (NS) 32 (0.001) 39
(0.001) 12-56
???? ? gt12 gt12 gt12 gt17.5 gt36 gt24 12-24 gt24
TTP ????
48
GOG 213-?????Robert Coleman
?????????? ????? gt6?
??
?
????
???
?????
?
?? ???
????? ???? ????????
GOG ?????TFI ?????
49
???????????
?????

15
20
30
30

???????????() ???????????() ???????????()
???? (?) Markman Gore Blackledge
0-6 17 10
7-12 27 17 29
13-18 33 27 63
19-24 33 27 94
gt24 59 57
Markman M, et al. J Clin Oncol.
19919(3)389-393. Gore ME, et al. Gynecol
Oncol. 199036207-211. Blackledge G, et al. Br J
Cancer. 198959650-653.
50
GOG ???????????II???

• ?? ?? ???/??
• 126-B ?? ????A 3/23 (13) ???
• 126-C ???? 3/30 (10) ???
• 126-D ????? 2/24 (8.4) ???
• 126-E PSC833 ??? 1/16 (6) ???
• 126-G CI-958 1/25 (4) ???
• 126-H ???? (24 h) 1/25 (4) ???
• 126-I 9-??-??? 8/58 (14)????
• 126-J ???? 13/58 (22) ?? (??????)

CDDP ?? GOG ?????
Bookman MA. Semin Oncol 200229(suppl 1)20-31.
51
GOG ???????????II???

• ?? ?? ???/??
• 126-K ???? 1/25 (4) ???
• 126-L ????/?? 9/57 (16) ????
• 126-M Ixabepilone 7/50 (14) ????
• 126-N ????? 10/48 (21) ??
• (??????)
• 126-O Triapine-?? ???
• 126-P ??? Celecoxib ????
• 126-Q ???? 10/48 (21) ??
• 126-R Abraxane ????????

CDDP c/s-diamminedichloroplatinum
(cisplatin) GOG gynecologic oncology group
Bookman MA. Semin Oncol 200229(suppl 1)20-31.
52
???????????????????GOG II?????
???????????????????,? ????????????????
???? 900 mg/m2 ??,?21??????????????,???????????1?
????????, ????????????????????
Day -7??, Vitamin B12 Day -6?? Day -5?? NSAID, ?? Days -4,-3?? Day -2?? NSAID, ?? Day -1????, ?? Day 1??, ????, ?? Day 2????,??
Miller DS, et al. ASCO 2008. Abstract 5524.
53
GOG???????II??? ????
?? ??? ??,
??
???? 1 2.1
???? 9 18.8
???? 17 35.4
???? 18 37.5
???? 3 6.3
?? 48 100
Miller DS, et al. ASCO 2008. Abstract 5524.
1 ????????.
54
???????????? Cochrane??

• 13 ??? (11????, 1 ?????II?????1????????)
• 568?????59 ? (10.4) ???????????????? (RR)
• RR ? 0?56????
• ???????,???8???356?????109?(30.6)?? ,?4??????
• ?????????? RR????, ????,???????????????
• ???????????????

RR ???
Williams CJ. Cochrane Database Syst Rev.
2000(2)CD001034.
55
GOG ???

• GOG 160 Trastuzumab
• GOG 170
• ????-12 (170B)
  Lapatinib (170G)
• Gefitinib (170C) Vorinostat (170H)
• Bevacizumab (170D) Temsirolimus (170I)
• Imatinib (170E) Enzastaurin (170J)
• Bay 43-9006 (170F) Mifepristone (170K)

????? ????? ???
GOG????? II???
GOG Gynecologic Oncology Group
56
????????????????
?? ?? ???? ????
VEGF-A VEGF-Trap VEGF-A, -B, -C, -D, -E, PIGF-1
? -2 ???? Volociximab ?5?1 integrin IMC-1121B
VEGFR-2 ?????????? Valatanib VEGFR-1, -2, -3,
PDGFR, and c-kit Sunitinib PDGFR, VEGFR-1, -2,
-3, c-kit, Flt-3 AMG-706 VEGFR-1, -2, -3,
PDGFR, and c-kit Sorafenib Raf, VEGFR-2, -3,
Flt-3, c-kit, PDGFR- ? ???????? Temsirolimus,
everolimus mTOR Enzastaurin PKC-
? Dasatinib Src ??
EGFR ???????? Mab ????? mTOR mammalian
target of rapamycin PDGF-R ??????????? PKC-b
???? C-beta VEGF ????????
57
??????????VEGF????????

• ????
• VEGF ?????????????????
• ????
• ????
• ????
• ?????????
• ?VEGF???
• ??????
• ???????
• ????????????

Han ES, et al. Expert Rev Anticancer Ther.
20077(10)1339-1345.Burger RA. J Clin Oncol.
200725(20)2902-2908.
VEGF ????????
58
?VEGF????????
VEGF
??? VEGFRs (VEGF-TRAP)
VEGFR-2
VEGFR-1
????
??????
VEGF ???????? VEGFR VEGF??
Podar K, et al. Blood. 2005105(4)1383-1395.
59
???? ??

• ??? (?? G1 G2)
• ??????
• ?? G1 ???
• ?? (??????) G2-G4 ?????? (?????????????)
• ????
• ??? (3 - 5)
• ???? ?? gt 65, ????????
• ???????????
• ????? ????
• ????? (?????????2 - 4 )
• ??????? 1

G1, G2 ????? GI ??? TE ????
Han ES, et al. Expert Rev Anticancer Ther.
20077(10)1339-1345.Burger RA. J Clin Oncol.
200725(20)2902-2908.
60
??????????II???
Cannistra 2007 Burger 2007 Garcia 2008
???? 44 62 70
????? ????? 2 52 3 48 1 34 2 66 Median 2 Range 1-3
??? 16 (PRs) 18 (PRs) 3 (CRs) 24 (PRs)
????? 11 0 6
?????? 7 0 4
?? 7 0 4
Cannistra SA, et al. J Clin Oncol.
200725(33)5180-5186.Burger RA, et al. J Clin
Oncol. 200725(33)5165-5171.Garcia AA, et al. J
Clin Oncol. 200826(1)76-82.
CR ???? GI ??? PR ????
61
???????????????????
?? ?????
Burger (GOG 170D) 0/62 (0)
Garcia (ASCO 2005) 2/29 (6.9)
Cannistra (ASCO 2006) 5/44 (11.4)
Wright (ASCO 2006) 4/62 (6.5)
Friberg (ASCO 2006) 2/13 (15.4)
Monk (Gyn Oncol 2006) 1/32 (3.1)
Wright (Cancer 2006) 2/23 (8.7)
Bidus (Gyn Oncol 2006) 0/3 (0)
Penson (ASCO 2006) 0/30
?? 16/298 (5.4)
GI ???
Han E, et al. Gynecol Oncol. 2007105(1)3-6.
62
NCI????II????? ?VEGF ??????
?? ?? ?? ??????? ??
MDA-2006-0329 AVE-0005 ???? ?? Coleman ???
NCT00129727 ?? (??????) MAb Penson ???
TEACO ?? ????/???? MAb Herzog ???
MCC-105366c ?? ???? MAb Wenham ???
ALSSOPR0501 ?? ????????? MAb Schwartzberg ???
NCT00343044 ?? ???? MAb McGonigle ???
NCT00267696 ?? ??/???? MAb Copeland ???
AVF3953 ?? IV ???/IP ? ???? MAb McMeekin ???
NCT00418093 ?? ????/???? MAb Horowitz ???
Bev ???? Carbo ?? Gem ???? IP ??? Mab
????? Ox ???? VEGF ????????
?? ??????
63
NCI ???? II?????VEGF EGFR ???
?? ?? ?? ??????? ??
NCI Bev Erlotinib MAb Friberg ???
NCT00130520 Bev Erlotinib MAb Alberts ???
NCT00520013 Bev /- Erlotinib ???? MAb Campos ???
Bev ???? EGFR ???????? Mab ????? VEGF
????????
64
NCI ???? II??????????????
?? ?? ?? ????? Status
GOG 170-J Enzastaurin (TKI) PKC -b Usha ??
NCT00391118 ?? /- Enzastaurin ? Enzastaurin PKC -b (???) ???
GOG 170-E Imatinib (TKI) PDGF-R Schilder ??
NCT00039585 Imatinib (TKI) PDGF-R Kohn ??
NCT00516841 Volociximab (MAb) ?5?1 Integrin ?? ???
NCT00479817 AMG 386 (Peptibody) Angiopoietins (???) ???
CT chemotherapy GOG gynecologic oncology
group EGFR ???????? Mab ????? PDGF-R
??????????? PKC-b ???? C-beta TKI ????????
65
???????????????????? ????

• ??, 2????? II?????

??RECIST?????????
??????? ?????lt 6???? ?????????????? 2? (N 40)
???? 10 mg/kg Days 1, 15 ????4 mg/m2 Days 1,
8, 15 28??????
????????? ?????????
????,??????????
??????????????gt 2?,?????????gt 2?
????????????,?????? 2 ?
McGonigle KF, et al. ASCO 2008. Abstract 5551.
66
??????????????(N 30)
???? ????
1.0
.75
.50
???????? ()
.25
0.0
0
2
4
6
8
10
12
14
16
18
20
?? (?)
McGonigle KF, et al. ASCO 2008. Abstract 5551.
67
????????????????????????????????
????????????(n 16)
1.0
????????????(n 14)
P .040 by log rank test
.75
.50
?????????? ()
.25
0.0
0
4
10
20
2
6
14
16
8
18
12
?? (?)
McGonigle KF, et al. ASCO 2008. Abstract 5551.
68
??????????????????????????????
????????? ???? (N 24) ???? (N 24) ???? (N 24)
????????? ????? ???? ???? ??
?????????? 5 9 14
?????????? 8 2 10
?? 13 11 24
McGonigle KF, et al. ASCO 2008. Abstract 5551.
69
?????????????????????????????
1.0
.75
.50
???? ()
???????????? (n 16)
.25
????????????(n 14)
P .043 by log-rank test
0.0
0
4
10
20
2
6
14
16
8
18
12
?? (?)
McGonigle KF, et al. ASCO 2008. Abstract 5551.
70
?????????????
0 3 6 12 18 24
?
? ? ? ?
????
????
????
????
???????????,????(CA 125) ??
71
????????

• ????????????
• ??????
• ???????????????, ???????????, ???????
• ????????,????

72
Thank you!