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Multidisciplinary treatment of rectal cancer. Medical oncology

Multidisciplinary treatment of rectal cancer. Medical oncology. Carlo Aschele E.O. Ospedali Galliera – Genova - Italy. ESMO CONFERENCE - LUGANO July 5-8 2007. Multidisciplinary treatment of rectal cancer. extraperitoneal rectal cancer locally advanced rectal cancer.

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Multidisciplinary treatment of rectal cancer. Medical oncology

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  1. Multidisciplinary treatment of rectal cancer. Medical oncology Carlo Aschele E.O. OspedaliGalliera – Genova - Italy ESMO CONFERENCE - LUGANOJuly 5-8 2007

  2. Multidisciplinary treatment of rectal cancer extraperitoneal rectal cancer locally advanced rectal cancer Rigid rectoscopy - TRUS - CT scan - MRI

  3. Standard treatment of locally advanced rectal cancer 45-50.4 Gy RT TME CT

  4. Role of chemotherapyPRE-OP RT +/- CONCOMITANT CT Bosset, NEJM 2006; Gerard, JCO 2006

  5. Role of chemotherapyPRE-OP RT +/- CONCOMITANT CT Bosset, NEJM 2006; Gerard, JCO 2006

  6. Standard treatment of locally advanced rectal cancer 45-50.4 Gy RT TME CT

  7. 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 9 0 2 4 6 8 1 3 5 7 0 2 4 6 8 1 3 5 7 9 Years since surgery Years since surgery Marijnen et al, GIASCO 2005, Abstr 166; Sauer et al NEJM 2004

  8. ROLE OF CHEMOTHERAPY POST-OP COMBINED-MODALITY TREATMENT (NCCTG 794751, 864751; NSABP R01, R02; INT 0114) n=3791 CT No CT Gunderson, L. L. et al. J Clin Oncol; 22:1785-1796 2004

  9. PRE-OP CHEMORADIATION: ORAL FP’s

  10. RT+ Capecitabine +/- oxaliplatin S R RT + CI 5-FU +/- oxaliplatin NSABP R-04 N=1460

  11. Decline in the rates of local failure: 1980s–2000s 35 30 25 20 15 10 5 0 Local failure (%) sx only sx  RT sx  CTRT TME + RT/CTRT

  12. Proportion of patients with distant metastases: 1980s–2000s 40 35 30 25 20 15 10 5 0 Distant metastases (%) sx only sx  RT sx  CTRT TME + RT/CTRT

  13. ONGOING STUDIES OF COMBINATION CHEMOTHERAPY IN LARC OXALIPLATIN + FP’s • Post-op E3201 E5204 Chronicle • Pre-op STAR NASBP R-04 • Pre and post-op PETACC-6

  14. Preliminary safety findings:toxicity (n=313) % of patients FU/RT FU/OXA/RT Grade III-IV toxicity (mainly diarrhoea) 10 24 Ability to complete radiotherapy (> 80 %)98 95 Ability to performsurgery 98 96 Aschele, ASCO GI & ASCO 2007

  15. PRE-OP CHEMORADIATIONINCORPORATION OF BIOLOGICS 2004-2007 • 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

  16. MULTIDISCIPLINARY TREATMENT OF RECTAL CANCER

  17. 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

  18. RT RT RT RT RT RT 5-FLUOROURACIL StudioTerapiaAdiuvanteRetto2 (PAN-STAR) Phase II n=70 Oxa Oxa Oxa Oxa Oxa Oxa PANPAN PAN PAN - T4 and/or - cN2 (> than 3 radiologically involved nodes) and/or- MRI prediction of +CRM

  19. D1 D1 D22 D22 …x4 …x4 D1 D1 D22 D22 …x4 …x4 Cape: 1650 mg/m2/d RT:45 Gy+ 9Gy boost Oxa: 130 mg/m2/d Cape: 2000 mg/m2/d Oxa: 130 mg/m2/d Cape: 2000 mg/m2/d Cetuximab: 400 mg/m2 D1 than 250 mg/m2 weekly INDUCTION CHEMOTHERAPY EXPERT-C Patients with MRI defined poor-risk rectal cancer T M E R Phase II n=164

  20. THANKS

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