Transcript Slayt 1

Kolon Kanserinde Adjuvan
Tedavi
Prof. Dr. N. Faruk AYKAN
TOD Kursu
Gaziantep
24 Ekim 2003
Prognosis by Stage
Stage
TNM
Dukes
5-yr survival
I
T1 N0 M0
A
>90%
I
T2 N0 M0
B1
85%
II
T3/4 N0 M0
B2/3
70-80%
III
T2 N1/2 M0
T3 N1/2 M0
T4 N1 M0
C1
C2
C3
25-60%
IV
Any T/N M1
D
5-30%
ESMO Guidelines 2001
Kolon Kanserinde Tedavi
Primer Tedavi : Cerrahi Rezeksiyon
(Hastaların % 50’si kürabl)
NCI-PDQ Statement March 2002
Kanser Tedavisinde Kanıt Düzeyleri
(NCI-2002)
Hedef
Çalışma Dizaynı
1. Randomize, kontrollü klinik
çalışmalar, metaanalizler
i. Çift kör
ii. Şemaya göre
2. Randomize olmayan klinik
çalışmalar
3. Olgu sunumları
i. Popülasyon, ardışık seri
ii. Ardışık seri
iii. Ardışık olmayan olgular
A.
B.
C.
D.
Total mortalite (GSK)
Nedene özgül mortalite
Yaşam kalitesi
Dolaylı veriler
i. Hastalıksız sağkalım
ii. Progresyonsuz
sağkalım
iii. Tümör cevap oranı
Source: US NCI 12-6-2002. http://www.nci.nih.gov / Cancer information PDQ
Level Of Evidence: How Is It Recorded?
DESIGN END POINTS
Example 1
Randomized, controlled (1)
1ii
A
Non-blinded (ii)
Overall survival (A)
Example 2
Non-randomized (2)
2ii
Di
Non-blinded (ii)
Disease-free survival (Di)
MAY BE USED FOR PRIMARY AND SECONDARY ENDPOINTS
Kolon Ca – Adjuvan KT
Evre III (Dukes’ C)
Kolon Ca – Adjuvan KT
Evre III (Dukes’ C)
5-FU/LEV
(12 ay)
5-FU/FA
(6 ay)
1990
NIH
1997
ASCO
?
2004
Kolon Ca – Adjuvan KT
Evre III (Dukes’ C)

Cerrahi
5-FU/Lev (12 ay)
(n:304)
>
Cerrahi
(n:315)
NCCTG 1989, INT-0035 1990 – 1995
Toplam vaka sayısı: 929
5 yıl HSK:
5 yıl GSK:
% 45 vs % 63
% 54 vs % 65
p<0.0001
p<0.007
Moertel CG et al: Ann Intern Med 122:321-326, 1995
(1iiA)
Kolon Ca – Adjuvan KT
Önerilen KT rejimi (1991)
Kolon Ca – Adjuvan KT
Evre III (Dukes’ C)

Cerrahi
5-FU/FA (6 ay)
n:158
>
Cerrahi
n:151
IMPACT 1995, INT-0085 1993-1997
Toplam vaka sayısı: 309
5 yıl HSK:
5 yıl GSK:
% 58 vs % 74
% 63 vs % 74
p<0.004
p<0.01
O’Connell et al: J Clin Oncol, 15:246-250, 1997
(1iiA)
Kolon Ca – Adjuvan KT
Evre III (Dukes’ C)
 Cerrahi
5-FU/FA (6 ay) = Cerrahi
(1iiA)
n: ?
INT-0089 1996 ve 1998
5-FU/Lev (12 ay)
n: ?
Toplam vaka sayısı: 3759
5 yıl HSK:
5 yıl GSK:
% 59 vs % 56
% 66 vs % 63
p:0.09
p:0.09
(5-FU/FA/Lev 6 ay FU/FA’dan üstün değil !)
Haller DG et al: Pro ASCO, 17:256a, 1998 (abstr.982)
Kolon Ca – Adjuvan KT
Standart KT rejimleri (ASCO 1997)
Mayo rejimi
Kolon Ca – Adjuvan KT
Standart KT rejimleri
Dublin - 2001
Adjuvant Chemotherapy For Stage III
Colon Cancer
• The oxaliplatin MOSAIC trial of LV5FU2 vs. FOLFOX4
recruited 1123 pts/arm
40% stage II patients
• 3-year DFS results were presented at ASCO 2003:
MOSAIC 3-year DFS
Overall
Stage II
Stage III
LV5FU2
72.9%
83.9%
65.5%
FOLFOX4
77.8%
86.6%
71.8%
P-value
P<.01
HR=.77
HR=.82
HR=0.76
De Gramont A, et al: Pro ASCO, abstr.1015, 2003
Oxaliplatin + 5-FU/FA
Adjuvan KT
•
•
•
•
•
NSABP C-01 : MOF ≥ Cerrahi (1988)
NSABP C-02 : PortalVİ 5-FU (7 gün) ≥ Cerrahi (1990)
NSABP C-03 : 5-FU/FA (12 ay) > MOF (1993)
NSABP C-04 : 5-FU/FA (6 ay) = 5-FU/Lev (12 ay) (1996)
NSABP C-05 : 5-FU/FA (6 ay) = 5-FU/FA/INFα-2a
• NSABP C-06 : UFT/FA vs 5-FU/FA (6 ay)
• NSABP C-07 : OXA/5-FU/FA vs 5-FU/FA
Irinotecan Adjuvant Clinical Development
Programme: Main Trials In Stage III Colon
Cancer
Trial
Regimen
Pts
Endpoints
400
3-yr DFS
Safety
Overall survival
CPT-11+LV5FU2
ACCORD 2
LV5FU2
PETACC-3
(V-307)
CPT-11+ inf 5-FU/FA
(LV5FU2 or AIO)
Inf 5-FU/FA
CPT-11+ capecitabine
QUASAR II
Bolus 5-FU/FA
3-yr DFS
Safety
2333 Overall survival
Translational res
3-yr DFS
Safety
3450 Overall survival
Translational res
Adjuvan KT’de infüzyonal 5-FU
PETACC-2 çalışması
LV5FU2, AIO
5-FU/FA*
*: Mayo klinik şeması
Irinotecan/5-FU/FA
Adjuvan KT’de
PETACC-3 çalışması
CPT-11/5-FU/FA*
5-FU/FA*
*: De Gramont, AIO şeması
PETACC-3 (V-307)
Group A1 (AIO, every wk)
Folinic acid
500 mg/m²
2 hours
60min
5-FU IV 2000 mg/m2
24 hours
CPT-11
80 mg/m2
Group A2 (LV5FU2, every 2 wks)
5-FU bolus
Folinic acid
200 mg/m² 400 mg/m2
2 hours
60min
CPT-11
180 mg/m2
5-FU IV 600 mg/m2
22 hours
D1 & D2
D1
Xeloda as adjuvant treatment for colon
cancer: X-ACT study
®
 Open-label, randomised, multicentre, phase III trial
 Recruitment of 1,956 Dukes’ C colon cancer
patients is on target for completion in 2001
 Xeloda 1,250mg/m twice daily, days 1–14 every
2
21 days x 8 versus 4-weekly Mayo Clinic
regimen x 6
 Disease-free survival as 1° endpoint
 2° endpoints: overall survival, safety, quality
of life, health economics, measurement of
biochemical markers in selected centres
Kolon Ca – Adjuvan KT
Evre II (Dukes’ B)
Kolon Ca – Adjuvan KT
Evre II (Dukes’ B)
 Cerrahi
5-FU/FA (6 ay) ≥ Cerrahi
(1iiDi)
% 2 HSK avantajı; NSABP ve Meta-analiz 1999
 Riskli sub-gruplar;






Perforasyon
Tam Obstrüksiyon
Anöploidi
Yüksek S-faz fraksiyonu
18q delesyonu
MSS
Kontrollü klinik çalışma !
Irinotecan Adjuvant Clinical Development
Programme: Other Studies
• CALGB C89803
• Irinotecan + bolus 5-FU/FA weekly vs bolus 5-FU/FA weekly
• 1263 patients, includes stage II + III and PS-2 patients
• 3-yr DFS, safety, overall survival, translational research
• AERO
• Irinotecan + LV5FU2 vs 5-FU/FA (Mayo Clinic or LV5FU2)
• 600 patients with stage II and III rectal cancer
• 5-yr DFS, safety, overall survival
• PETACC-4
• Irinotecan + 5-FU/FA (TTD, LV5FU2, AIO) vs 5-FU/FA
• 1976 patients with stage II colon cancer
• 5-yr DFS, safety, overall survival, translational research