Multidisciplinary treatment of rectal cancer' Medical oncology

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Multidisciplinary treatment of rectal cancer.
Medical oncology

• Carlo Aschele
• E.O. Ospedali Galliera Genova - Italy

ESMO CONFERENCE - LUGANO July 5-8 2007
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Multidisciplinary treatment of rectal cancer

• extraperitoneal rectal cancer
• locally advanced rectal cancer

Rigid rectoscopy - TRUS - CT scan - MRI
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Standard treatment of locally advanced rectal
cancer
45-50.4 Gy
RT
TME
CT
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Role of chemotherapyPRE-OP RT /- CONCOMITANT CT
Bosset, NEJM 2006 Gerard, JCO 2006
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Role of chemotherapyPRE-OP RT /- CONCOMITANT CT
Bosset, NEJM 2006 Gerard, JCO 2006
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LARC standard treatment
RT
Sx
1990
FU
CRM assessment
TME
PRE-OP RT
RT
2004
TME
FU
FU
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Standard treatment of locally advanced rectal
cancer
45-50.4 Gy
RT
TME
CT
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Dutch TME trial vs German trial 5-year overall
survival
1.0
1.0
Post-op CMT
RT TME
Pre-op CMT
TME alone
0.6
0.6
66 vs 65 p 0.98
76 vs 74 p 0.80
0.2
0.2
0
0
0
2
4
6
8
9
1
3
5
7
0
2
4
6
8
1
3
5
7
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Years since surgery
Years since surgery
Marijnen et al, GIASCO 2005, Abstr 166 Sauer et
al NEJM 2004
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ROLE OF CHEMOTHERAPY POST-OP COMBINED-MODALITY
TREATMENT
(NCCTG 794751, 864751 NSABP R01, R02 INT 0114)
n3791
CT
No CT
Gunderson, L. L. et al. J Clin Oncol
221785-1796 2004
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PRE-OP CHEMORADIATION ORAL FPs
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NSABP R-04
N1460
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Decline in the rates of local failure
1980s2000s
35 30 25 20 15 10 5 0
Local failure ()
sx only sx ? RT sx ? CTRT TME RT/CTRT
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Proportion of patients with distant metastases
1980s2000s
40 35 30 25 20 15 10 5 0
Distant metastases ()
sx only sx ? RT sx ? CTRT TME RT/CTRT
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ONGOING STUDIES OF COMBINATION CHEMOTHERAPY IN
LARC
OXALIPLATIN FPs

• Post-op E3201 E5204 Chronicle
• Pre-op STAR NASBP R-04
• Pre and post-op PETACC-6

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Rationale for incorporation of new agents in the
treatment of rectal cancer

• To improve control at distant sites
• To improve R0 resection rates (esp. big T3, T4
  and tethered tumours)
• To enhance down-sizing and SPS
• (Potential) prognostic value of pCR and
  down-staging

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Preliminary safety findingstoxicity (n313)
of patients FU/RT
FU/OXA/RT Grade III-IV toxicity (mainly
diarrhoea) 10 24 Ability to
complete radiotherapy (gt 80 )
98 95 Ability to performsurgery
98 96
Aschele, ASCO GI ASCO 2007
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PRE-OP CHEMORADIATIONINCORPORATION OF BIOLOGICS
2004-2007

• Cetuximab
• FU (1) pCR12 cape (1) pCR5 cape/ox
  (1) pCR8 cape/iri (2) pCR25-20
• ?? adksquamous - 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

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MULTIDISCIPLINARY TREATMENT OF RECTAL CANCER
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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

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Studio Terapia Adiuvante Retto 2 (PAN-STAR)
Phase II n70
Oxa Oxa Oxa Oxa
Oxa Oxa
PAN PAN PAN PAN
- T4 and/or - cN2 (gt than 3 radiologically
involved nodes) and/or- MRI prediction of CRM
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INDUCTION CHEMOTHERAPY
EXPERT-C
Patients with MRI defined poor-risk rectal cancer
T M E
R
Phase II n164
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THANKS
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