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Multidisciplinary treatment of rectal cancer. Medical oncology
Multidisciplinary treatment of rectal cancer. Medical oncology
Carlo AscheleE.O. Ospedali Galliera – Genova - Italy
Carlo AscheleE.O. Ospedali Galliera – Genova - Italy
ESMO CONFERENCE - LUGANO July 5-8 2007
Multidisciplinary treatment of rectal cancer
Multidisciplinary treatment of rectal cancer
extraperitoneal rectal cancer
locally advanced rectal cancer
extraperitoneal rectal cancer
locally advanced rectal cancer
Rigid rectoscopy - TRUS - CT scan - MRI
Standard treatment of locally advanced rectal cancer
Standard treatment of locally advanced rectal cancer
TME
45-50.4 Gy
CT
RT
Role of chemotherapyPRE-OP RT +/- CONCOMITANT CT
Role of chemotherapyPRE-OP RT +/- CONCOMITANT CT
pCR, %
RT RT + CT
EORTC 5 14
FFCD 3 10
Bosset, NEJM 2006; Gerard, JCO 2006
Role of chemotherapyPRE-OP RT +/- CONCOMITANT CT
Role of chemotherapyPRE-OP RT +/- CONCOMITANT CT
5-y LR, %
RT RT + CT
EORTC 17 8
FFCD 16 8
Bosset, NEJM 2006; Gerard, JCO 2006
Standard treatment of locally advanced rectal cancer
Standard treatment of locally advanced rectal cancer
TME
45-50.4 Gy
CT
RT
Dutch TME trial vs German trialDutch TME trial vs German trial5-year overall survival
Pre-op CMTPre-op CMT
Post-op CMTPost-op CMT
Years since surgeryYears since surgery
66 % vs 65 % 66 % vs 65 % p = 0.98p = 0.98
Marijnen et al, GIASCO 2005, Abstr 166; Sauer et al NEJM 2004
00 11 22 33 44 55 66 77 88 9900
0.20.2
0.60.6
1.01.0
00 11 22 33 44 55 66 77 88 9900
0.20.2
0.60.6
1.01.0
Years since surgeryYears since surgery
RT + TMERT + TME
TME aloneTME alone
76 % vs 74 %76 % vs 74 % p = 0.80p = 0.80
Gunderson, L. L. et al. J Clin Oncol; 22:1785-1796 2004
(NCCTG 794751, 864751; NSABP R01, R02; INT 0114) n=3791
ROLE OF CHEMOTHERAPY ROLE OF CHEMOTHERAPY POST-OP COMBINED-MODALITY POST-OP COMBINED-MODALITY
TREATMENTTREATMENT
CT
No CT
PRE-OP CHEMORADIATION: ORAL FP’s
PRE-OP CHEMORADIATION: ORAL FP’s
studies patients pCR(%)
g 3-4 tox(%)
Capecitabine 14 668 4-31 6-40
UFT 11 538 8-25 6-32
Eniluracile 1 22 6 nr
NSABP R-04NSABP R-04
RTRT + + CapecitabineCapecitabine +/- oxaliplatin +/- oxaliplatin
S
RT + RT + CI 5-FUCI 5-FU +/- oxaliplatin +/- oxaliplatin
R
N=1460
Norway NSABP-R01 GITSG-1 Mayo-NCCTGGITSG-2 INT-0114 NSABP-R02 INT-PVIDutch-TME Ulsan CAO/ARO/AIO
Decline in the rates of local failure: 1980s–2000sDecline in the rates of local failure: 1980s–2000s
35
30
25
20
15
10
5
0
Lo
cal
fail
ure
(%
)
sx only sx RT sx CTRT TME +RT/CTRT
NSABP-R02 INT-0114 Norway GITSG-1NSABP-R01 Mayo-NCCTG INT-PVI GITSG-2Dutch-TME Ulsan CAO/ARO/AIO
Proportion of patients with distant metastases: 1980s–2000sProportion of patients with distant metastases: 1980s–2000s
40
35
30
25
20
15
10
5
0
Dis
tan
t m
etas
tase
s (%
)
sx only sx RT sx CTRT TME +RT/CTRT
ONGOING STUDIES OF COMBINATION CHEMOTHERAPY IN LARC
ONGOING STUDIES OF COMBINATION CHEMOTHERAPY IN LARC
Post-op E3201E5204Chronicle
Pre-op STARNASBP R-04
Pre and post-op PETACC-6
Post-op E3201E5204Chronicle
Pre-op STARNASBP R-04
Pre and post-op PETACC-6
OXALIPLATIN + FP’s
% of patients
FU/RT FU/OXA/RT
Grade III-IV toxicity(mainly diarrhoea) 10 24
Ability to completeradiotherapy (> 80 %) 98 95
Ability to performsurgery 98 96
Preliminary safety findings:toxicity (n=313)
Aschele, ASCO GI & ASCO 2007
PRE-OP CHEMORADIATIONINCORPORATION OF BIOLOGICS
PRE-OP CHEMORADIATIONINCORPORATION OF BIOLOGICS
Cetuximab+ FU (1) pCR=12%+ cape (1) pCR=5%+ cape/ox (1) pCR=8%+ cape/iri (2)pCR=25-20%
??: adk=squamous - ras - arrest of cell cycle progression
Bevacizumab+ FU (1) no pCR at the RD / surrogate markers+ cape/oxa (1) pcR: 18%
??: toxicity - normalization vs antivascular effect - timing
Cetuximab+ FU (1) pCR=12%+ cape (1) pCR=5%+ cape/ox (1) pCR=8%+ cape/iri (2)pCR=25-20%
??: adk=squamous - ras - arrest of cell cycle progression
Bevacizumab+ FU (1) no pCR at the RD / surrogate markers+ cape/oxa (1) pcR: 18%
??: toxicity - normalization vs antivascular effect - timing
2004-2007
MULTIDISCIPLINARY TREATMENT OF RECTAL CANCER
MULTIDISCIPLINARY TREATMENT OF RECTAL CANCER
PRE-OP CHEMORADIATIONINCORPORATION OF BIOLOGICS
PRE-OP CHEMORADIATIONINCORPORATION OF BIOLOGICS
Better understanding of underlying biology
Definition of optimal timing and duration (induction vs concomitant or both)
Definition of an appropriate back-bone regimen
Patient selection
Better understanding of underlying biology
Definition of optimal timing and duration (induction vs concomitant or both)
Definition of an appropriate back-bone regimen
Patient selection
Studio Terapia Adiuvante Retto 2 (PAN-STAR)
Studio Terapia Adiuvante Retto 2 (PAN-STAR)
Oxa Oxa Oxa Oxa Oxa Oxa
5-FLUOROURACIL
RT RTRT RT RT RT
PAN PAN PAN PAN
- T4 and/or - T4 and/or - cN2 (> than 3 radiologically involved nodes) and/or- cN2 (> than 3 radiologically involved nodes) and/or- MRI prediction of +CRM - MRI prediction of +CRM
Phase IIn=70
INDUCTION CHEMOTHERAPYINDUCTION CHEMOTHERAPY
D1 D22
…x4
Patients with MRI defined poor-risk rectal cancer
T
M
E
RD1 D22
…x4
D1 D22
…x4
D1 D22
…x4
Oxa: 130 mg/m2/d
Cape: 2000 mg/m2/d
Cetuximab: 400 mg/m2 D1 than 250 mg/m2 weekly
Cape: 1650 mg/m2/d
RT:45 Gy+ 9Gy boost Oxa: 130 mg/m2/dCape: 2000 mg/m2/d
Phase IIn=164
EXPERT-C
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