M.

Oukkal

Clinique dOncologie Mdicale Amine Zirout CHU Bni-Messous - Alger Ouest

Sakuramoto S et al. NEJM 2007; 357 (18): 1810-20

Sakuramoto S et al. NEJM 2007; 357 (18): 1810-20

 Efficacit confirme pour les asiatiques

(Etude CLASSIC) Option en absence de chimiotrapie priopratoire (Magic study) ou de Radiochimiothrapie post opratoire (Mc Donald)

Mc Donald JS et al. N Engl J Med 2001; 345(10) : 725-30

Mc Donald JS et al. N Engl J Med 2001; 345(10) : 725-30

Modernisation du Mc Donald = Amliore la tolrance pas lefficacit

CS Fuchs et al. ASCO 2011; LBA 403

D Cunningham et al. NEJM 2006; 355 (10)

CT priopratoire = standard de traitement des formes localises

D Cunningham et al. NEJM 2006; 355 (10)

#Pat Murad 1993 Pyrhnen 1995 Scheithauer 1995 BSC* FAMTX BSC FEMTX BSC F/L/Epi 10 30 20 21 19 18

Survie 3 mois 10 mois 3 mois 12.3 mois 4 mois + 7.5 mois

p-value

0.001

< 0.0006

0.05

Glimelius 1997

BSC ELF

30 31

5 mois 8 mois

0.12

R A N D O M I S A T I O N

457 patients with metastatic gastric cancer

A: Docetaxel: 75 mg/m2 D1 Cisplatin: 75 mg/m2 D1 5FU: 750 mg/m2 IVC D1 to D5 B: Cisplatin: 100 mg/m2 D1 5FU: 1,000 mg/m2 IVC D1 to 5

Moiseyenko et al, ASCO 2005, Abstract 4002

OR

TTP (months)

OS (months)

Grade 3-4 toxicity

DCF CF

221/227 224/230

37%

5.6

9.2

Diarrhoea, infection, neutropaenia

Stomatitis Renal toxicity

25%
p=0.01

3.7
p=0.0004

8.6
p=0.02

In DCF arm: grade 3-4 toxicity included: 81% non-haematologic, 75% haematologic with 30% febrile neutropaenia DCF could be a new therapeutic option but: cave toxicities CF is probably not the best reference arm.
Moiseyenko et al, ASCO 2005, Abstract 4002

Stratification:
Center Liver mets (yes vs no) Gastrectomy (yes vs no) Measurable vs evaluable only Weight loss (5% vs >5%)

R A N D O M I S A T I O N

IF arm: 170 patients

FA: 500 mg/m2 5FU: 2,000 mg/m2 as 22 h CI Irinotecan: 80 mg/m2
Given weekly for 6 weeks q 7 weeks

CF arm: 163 patients

5FU: 1,000 mg/m2 as 24 h CI x 5d CDDP: 100 mg/m2 day 1
Given q 4 weeks

Dank et al, ASCO 2005, Abstract 4003.

Phase III studies with irinotecan: IF vs CF - 2

Best overall response
CR PR Overall response 5 49 54 IF n=170 n (%) (2.9%) (28.8%) (31.8%) 1 41 42 CF n=163 n (%) (0.6%) (25.2%) (25.8%)

NC/SD
Tumour control (CR/PR/SD) PD Not evaluable

62
116 38 16

(36.5%)
(68.2%) (22.4%) (9.4%)

55
97 37 29

(33.7%)
(60.0%) (22.7%) (17.8%)

Dank et al, ASCO 2005, Abstract 4003.

Phase III studies with irinotecan: IF vs CF - 3

Grades 3/4 Safety population Neutropaenia Febrile neutropaenia/ neutropaenic Infection Leukopaenia Anaemia Thrombocytopaenia IF n=167 % 25 5 16 11 2 CF n=166 % 52 10 25 17 12

Dank et al, ASCO 2005, Abstract 4003.

D Cunningham et al. ASCO 2006

D Cunningham et al. ASCO 2006

D Cunningham et al. ASCO 2006

CS. H. Park et al. ASCO 2011

CS. H. Park et al. ASCO 2011

Trastuzumab = TOGA Study Bevacizumab = AVAGAST Study

Phase III, randomized, open-label, international, multicenter study

3807 patients screened1 810 HER2-positive (22.1%) HER2-positive advanced GC (n=584)

5-FU or capecitabinea + cisplatin (n=290) R 5-FU or capecitabinea + cisplatin + trastuzumab (n=294)

Primary end point: Overall survival Secondary end points PFS, TTP, ORR, Clinical Benefit Rate, Duration of Response, QoL.
E Van Cutsem et al. ASCO 2009

Nouveau standard de 1re ligne des cancers gastriques Her2 positifs

E Van Cutsem et al. ASCO 2009

Y. Kang et al. ASCO 2010

Essai ngatif = Bevacizumab non recommand en routine Y. Kang et al. ASCO 2010

 La chimiothrapie adjuvante (Asie)

La radiochimiothrapie adjuvante (Amrique)

La chimiothrapie pri-opratoire (Europe) La chimiothrapie palliative > BSC

Drogues plus rcentes (Docetaxel Irinotecan

Oxaliplatin capecitabine) 2me et 3me ligne de traitement Les thrapies cibles (Trastuzumab) Her2 positifs