Gastric cancer discussion slides final version.pptnew.ppt


Published on

Published in: Health & Medicine
  • Be the first to comment

No Downloads
Total views
On SlideShare
From Embeds
Number of Embeds
Embeds 0
No embeds

No notes for slide

Gastric cancer discussion slides final version.pptnew.ppt

  1. 1. Gastric Cancer: Discussion Prof David Cunningham Royal Marsden Hospital United Kingdom
  2. 2. Issues highlighted by these cases Optimal management of early stage gastric cancer with regards to…… staging peri-operative treatment surgery Role of chemotherapy in advanced gastric cancer
  3. 3. Operable Disease: Staging Local assessment Assessment for distal disease Endoscopy (diagnostic) CT Thorax/abdomen/pelvis EUS Laparoscopy – Local staging and – identifies CT occult assessing proximal & metastatic disease distal extent of (OGJ) tumour Improve selection of – Staging accuracy ~75% patients for radical Rx in gastric cancer1 PET can provide additional information regarding local and distal disease less sensitive but more specific than CT2 for local LN metastases ● limitation ~30% of gastric cancer are non-FDG avid3 ● potential role for early response assessment to neo-adjuvant Rx ●1. Abdalla & Pisters, Seminars in Oncology 2004 2. Kim et al, Eur J Nucl Med Mol Imaging 2006 3. Ott et al., Clin Cancer Res 2008
  4. 4. Peri-operative Chemotherapy: The MRC MAGIC Trial Post- Pre-operative Surgical operative Resectable ECX x3 resection ECX x3adenocarcinoma of within 3-6/52 Randomised within 6-the stomach, OGJ 12/52 or lower Surgicaloesophagus n=503 resection within 6/52 Median OS: 24 v 20 months 5 yr OS: 36% v 23% 13% OS benefit for ECF HR for death 0.75, p=0.009 Pre-op chemo well tolerated (5% did not complete pre-op Rx due to toxicity) No increase in post-op complications Cunningham et al., NEJM 2006
  5. 5. Peri-operative Rx:Advantages Disadvantages Increase rate of curative (R0) Risk of disease progression during resection1 by tumour pre-operative treatment downstaging/downsizing Definitive surgery may be delayed if Eradication of micro-metastatic significant toxicity occurs disease Risk of increased peri-operative Demonstrates in vivo chemo- morbidity - NOT seen in the sensitivity MAGIC2 trial Better tolerated than post- operative therapy – MAGIC2 Peri-operative chemotherapy is -91% pts able to complete pre- now standard of care in Europe op Rx -66% of pts able to commence post-op Rx1. Boige et al., ASCO 2007 2. Cunningham et al., NEJM 2006
  6. 6. Post-operative Chemoradiation: SWOG 9008/Intergroup 0116 TrialResected stage Ib-IV (M0) Observation n=275 gastric or OGJ adenocarcinoma n=556 Randomised (<D1 resection 54% 5-FU/LV Chemoradiation D1 = 36%, D2 = 10%) (4500Gy) n=281 Median OS: 27 v 36m HR for death 1.35; p=0.006 Highly selected population (All had R0 resection + recovered from surgery) yet only 64% completed Rx Significant Rx related toxicity: 1% toxic death 73% grade 3/4 AEs Macdonald et al., NEJM 2001
  7. 7. Adjuvant Chemotherapy: ACTS-GT1 Observation n=530 Stage II-III gastric cancer treated with curative Randomisedgastrectomy; all with at least D2 Adjuvant S-1 80mg/m2/day dissection n=1059 x28 days q 6 weeks x 12 months n=529 Screening programme in Japan allows detection of disease at an earlier stage S1 efficacy not proven in non- Asian population 3 yr OS: 81.1% v 70.1% Meta-analysis adjuvant Rx2: HR for death 0.68, p=0.003 Despite selected nature of the pt population, benefit of adjuvant chemo is modest (Relative risk of death 0.85, 95% CI 0.80-0.90) 1. Sakuramoto et al., NEJM 2007, 2. Liu et al., Eur J Surg Oncol 2008
  8. 8. Surgery: Extended D2 Lymph nodedissectionD2 v D1 resection no survival advantage namely due to excess morbidity and mortality related to distal pancreatectomy & splenectomy1,2,3 D2 dissection without distal pancreatectomy & splenectomy by an experienced surgeon at a high volume centre is recommended current clinical practice1.Cuschieri et al., BJC 1999, 2. Bonenkamp et al., NEJM 1999 Hartgrink et al., JCO 2004
  9. 9. Metastatic Gastric Cancer:The Role of Chemotherapy Survival with best supportive care (BSC) alone ~3 months1,2 Combination chemotherapy improves OS compared to BSC (HR 0.39, 95% CI 0.28-0.52, p<0.00001)3 Benefit in weighted mean average survival ~ 6 months31. Murad et al., Cancer 1993, Pyrhonen et al., BJC 995 3. Wagner et al., JCO 2006
  10. 10. Selection of patients for chemotherapy Patients of good performance status (ECOG 0-1) more likely to respond to chemotherapy1 and have improved median survival1,2 Linitus plastica is a feature of poor prognosis1 Response rate is lower in patients with peritoneal carcinomatosis3 Co-morbidities must be consideredRougier et al., EJC 1994 2. Lavin et al, Cancer 1982 3. Preusser et al., JCO 1989
  11. 11. Selection of chemotherapy for patients1 Combination chemotherapy superior to monotherapy for OS HR 0.83 (0.74-0.93) OS is superior with the addition of anthracyclines to platinum/ HR 0.77 (0.62-0.95) fluorouracil1. Wagner et al., JCO 2006
  12. 12. REAL 2 Epirubicin Cisplatin + infused 5-FU (ECF) Randomised Untreated advanced Epirubicin + cisplatin + capecitabine (ECX) oesophageal,OGJ or gastriccancer n=1002 Epirubicin + oxaliplatin + 5-FU (EOF) Epirubicin + oxaliplatin + capecitabine (EOX) Primary Endpoints: Non-inferiority for survival Capecitabine compared to Fluorouracil Oxaliplatin compared to Cisplatin Overall survival amongst the four regimens Cunningham et al., NEJM 2008
  13. 13. REAL-2 - Results HR 0.86 (0.8 – 0.99) Capecitabine is non-inferior to infused 5FU Toxicity: More G3/4 neutropenia (uncomplicated) hand foot syndrome Oxaliplatin is non-inferior to cisplatin HR 0.92 (0.8 – 1.10) Toxicity: Less G3/4 neutropenia (uncomplicated) thromboembolism, alopecia More G3/4 diarrhoea G3/4 peripheral neuropathyCunningham et al., NEJM 2008
  14. 14. Survival: ECF v EOX Arm OS (m) 1 year survival p-value HR (95% CI) (95% CI) ECF 9.9 37.7 (31.8-43.6) EOX 11.2 46.8 (40.4-52.9) 0.020 0.80 (0.66-0.97)Improved efficacy of EOX compared to ECF for survival EOX now an accepted first-line therapy optionCunningham et al., NEJM 2008
  15. 15. V-325 phase III trial: DCF Docetaxel +cisplatin + Untreated advanced infused 5-FU gastric cancer Randomised (n=445) Cisplatin + infused 5-FU Primary objective: Superior TTP with DCF relative to FP Results: TTP 5.6m v 3.7m HR 1.47; p<0.001 OS 9.2m v 8.6m HR 1.29; p=0.02 BUT Grade 3/4 AEs* All 69 v 59% *Neutropenia 82 v 57%, complicated neutropenia 29 v 12%Van Cutsem et al., JCO 2006
  16. 16. DCF….…reducing toxicity ATTAX - randomised phase II trial Weekly docetaxel Untreated advanced 30mg/m2 D1, D8 + gastric cancer Randomised cisplatin 60mg/m2 D1 + infused 5-FU 200mg/m2/day DCF DX (n=50) (n=56) Weekly docetaxel 30mg/m2 D1, D8 + Confirmed RR 47% 26% capecitabine 1600mg/m2 D1-14 q21d Median PFS 5.8 4.6 Median OS 11.4 10.5 Toxicity: 4% febrile neutropenia with DCF, 2% with DCX DCF with weekly docetaxel may be an alternative, less toxic regimenTebbutt et al., ASCO 2007
  17. 17. Second Line Chemotherapy No current phase III data to support 2nd line chemotherapy Patients sustaining prolonged benefit from first-line chemotherapy may be re-challenged with the same regimen on progression Phase II data: Response rates are low, but selected patients may benefit from second-line chemotherapy Treatment n RR Median TTP or Median OS/ PFS /months months Docetaxel1 49 16% 2.5 8.3 (75mg/m2 q3 weeks) FOLFIRI2 38 29% 3.7 6.4 Irinotecan3 37 20% 2.6 5.2 (125m/m2 d1, 8,15 q4 weeks) Irinotecan (160mg/m2) + 49 20% 2.7 8.9 docetaxel (65mg/m2)41. Lee et al., Cancer Chemother Pharmacol 2008, 2. Assersogn et al., Ann Oncol 2004, 3. Chun et al.,Jpn J Clin Oncol 2004, 4. Sym et al., Cancer Chemother Pharmacol 2008
  18. 18. Current randomised phase III trials ECX x3 Surgery ECX x3 ST03 (MAGIC-B) Resectable adenocarcinoma of the ECX + ECX + Surgerystomach or Type III OGJ bevacizumab x3 bevacizumab x3 CRITICS: ECX x3 Surgery ECX x3 Resectable adenocarcinoma of thestomach or Type III OGJ ECX x3 Surgery CX +RT 45Gy EOX REAL3Untreated advanced adenocarcinoma or undifferentiated carcinoma of the EOX oesophagus, OGJ or stomach panitumumab