1. Challenging Cases in Cancer: Integration of Findings from ASCO 2007 Gastric Cancers David H. Ilson, MD, PhD Associate Attending Physician GI Oncology Service Memorial Sloan-Kettering Cancer Center New York, NY

2. Upper GI Cancer: US Incidence in 2007 93,150 new cases gastric, esophageal, pancreatic, hepatobiliary cancer –8% of new cancers –81% fatality rate –15% of American cancer deaths Decline in gastric cancer incidence Increase in esophageal, GE JX, cardia adeno Increase in hepatocellular Ca Jemal et al, CA Cancer J Clin 57: 43-66; 2007

3. Gastric Cancer: Current Therapy Adjuvant –Post op 5-FU/LV + RT: increases 5-yr OS by 10% (U.S. Standard, INT 116) –Pre and Post op ECF: increases 5-yr OS by 13% (U.K. Standard, MAGIC trial)

4. Case 1: GE Junction Adenocarcinoma A 79-year-old male presents with increasing dysphagia, 15 pound weight loss, odynophagia Past history: NIDDM, BPH, hypercholesterolemia EUS: T3N1 adenocarcinoma, 50% circumferential CT scan: distal esophageal mass PET scan: uptake in the primary, SUV The patient is admitted from clinic for complete dysphagia, and has endoscopy and Polyflex stent placement

5. Case 1: GE Junction Adenocarcinoma PET scan CT scan

6. Which treatment option would you recommend?  Esophagectomy  Preop chemotherapy with ECF followed by esophagectomy and post op ECF  Preop combined chemoradiotherapy followed by surgery  Primary combined chemoradiotherapy without surgery Case 1: GE Junction Adenocarcinoma

7. The patient received induction chemo with weekly carboplatin and paclitaxel for 3 treatments. Dysphagia improved post stent and with chemotherapy PET scan: response to induction chemo (SUV 9.7  5.3), EGD: response, stent was removed Combined chemotherapy with weekly carbo/paclitaxel and RT 5040 cGy was administered EGD post therapy x 2 (4 and 8 weeks after RT): treatment related stricture dilated, biopsy negative Repeat PET scan 2 months post RT: SUV further reduced, 3.1 Surgery deferred PET 1PET 2 PET 3

8. Case 1: GE Junction Adenocarcinoma

9. GE Junction and Esophageal Cancer: Adjuvant Therapy Survival with surgery alone: 20-40% Adjuvant trials in esophageal cancer have evaluated preop therapy –Preop Chemotherapy –Preop Chemo + radiotherapy »Most common U.S. practice

10. Esophageal Cancer: Preop Chemotherapy Negative Trials U.S. INT 113 –3 pre, 3 post op cycles of 5-FU + Cisplatin –440 pts –Adeno 54%, Squamous 46% –No improvement in R0 resection rate, disease free or overall survival –Path CR 2.5% Kelsen et al, NEJM 339: 1979; 1998

11. Esophageal Cancer: Preop Chemotherapy Positive trials U.K. MRC OEO-2 –2 preop cycles of 5-FU + Cisplatin –802 pts –Adeno 66%, Squamous 31% –6% increase in R0 resection rate, 9% increase in 2-year OS –Path CR 4% U.K. MAGIC: pre and post op ECF in gastric cancer –25% of 500 pts had GE junction or distal esophageal adeno –No improvement in R0 resection rate, 13% increase in 5-year OS –No Path CRs MRC Lancet 359: 1727; 2002, Cunningham NEJM 355: 11; 2006

12. Esophageal Cancer: Consensus on Adjuvant Therapy Something more than surgery alone should be done Adenocarcinoma –Preoperative chemotherapy improves overall survival »MAGIC: 13% improvement at 5 yr »MRC 0E0-2: 9% improvement at 2 yr –No clear impact on rate of R0 resection Addition of RT to chemotherapy –Improves rates of curative resection in some trials –Achieves pathologic complete responses in 10-30% –Phase III trials: only 2 of 5 recent trials showed a survival benefit for preop chemo + RT MRC Lancet 359: 1727; 2002, Cunningham NEJM 355: 11; 2006

13. Preop Chemo in Esophageal and Gastric Cancer: FFCD / FNLCC Preop CT (2-3 cycles) (N = 98) 89% Surgery (N = 109) 96% Postop CT (N = 145) S (N = 111) Surgery (N = 110) 99% CT + S (N = 113) CT = 5-FU + Cisplatin Boige, et al. ASCO 2007. Abstract 4510

14. Surgical and Pathological Results S N = 110 CT = S N = 109 No. pts (%) Extent of resection No. resection 10 (9)7 (6) R0 81 (74)95 (87)P = 0.04 R1 6 (5)4 (4) R2 12 (11)2 (2) RX 1 (1) Boige, et al. ASCO 2007. Abstract 4510

15. Overall Survival 5-year DFS: 24% (16 - 33%) vs. 38% (28 - 47%) Boige, et al. ASCO 2007. Abstract 4510

16. Disease-free Survival Boige, et al. ASCO 2007. Abstract 4510 5-year DFS: 21% (14 - 30%) vs. 34% (26 - 44%)

17. Preop Chemotherapy in Esophageal Adenocarcinoma Survival benefit for preop chemotherapy with CF (cisplatin and 5-FU) 14% improvement in 5-yr OS, HR 0.69 –Similar to survival for gastric cancer in MAGIC trial 13% rate of improvement in R0 resection rate Impact on tumor downstaging: not statistically significant Boige, et al. ASCO 2007. Abstract 4510

18. Preop Chemotherapy in Esophageal Adenocarcinoma Major impact was reduction in systemic recurrence –Systemic: 56% for surgery  42% for chemo + surgery –Local: 26% for surgery = 24% for chemo + surgery Similar results for CF compared to ECF-MAGIC –Epirubicin may not be needed Role of epirubicin? –OEO-05 (U.K. MRC) –Preop ECF vs. CF in esophageal cancer Boige, et al. ASCO 2007. Abstract 4510

19. Preop Chemotherapy in Esophageal Adenocarcinoma Preop Chemo in esophageal and GE JX adeno improves survival Relative small sample 224 pts, differences of 10-15% come down to outcomes in only 10-15 patients Preoperative staging –EUS not performed –Accuracy of pre-therapy stage ? –No stratification for stage Boige, et al. ASCO 2007. Abstract 4510

20. Individual Patient Data-based Meta-analysis Assessing Pre-operative Chemotherapy in Resectable Oesophageal Carcinoma Individual patient data from preop chemo trials (esophageal squamous and adenocarcinoma) 9 trials OS (2102 pts) 7 trials DFS (1849 pts) 2 dominant trials: –U.S. INT 113 (467 pts) –U.K. MRC OEO-2 (802 pts) Slightly more than 50% of patients had squamous ca Preop Chemo: Overall survival improvement with a HR of 0.87 (P = 0.0033) –Translates into 4.3% improvement in OS at 5-yrs Thirion P, et al. ASCO 2007. Abstract 4512

21. Primary End-point: Overall Survival Thirion P, et al. ASCO 2007. Abstract 4512

22. Secondary End-point: DFS Thirion P, et al. ASCO 2007. Abstract 4512

23. Individual Patient Data-based Meta-analysis Assessing Pre-operative Chemotherapy in Resectable Oesophageal Carcinoma Although overall survival benefit independent of histology –Adeno:20%  27% –Squamous:16%  20% Other endpoints: –R0 resection rate improved by 5% –Post Operative Mortality: not increased with preop chemo Conclusions: Preop chemotherapy –Modest improvement in 5-yr OS (4.3%) –Greater effect for adenocarcinoma then squamous cell carcinoma of the esophagus Thirion P, et al. ASCO 2007. Abstract 4512

24. Preoperative Chemotherapy (CTX) Versus Preoperative Chemoradiotherapy (CRTX) In Locally Advanced Esophagogastric Adenocarcinomas: First Results of A Randomized Phase III Trial M. Stahl, M. K. Walz, M. Stuschke, N. Lehmann, M. H. Seegenschmiedt, J. Riera Knorrenschild, P. Langer, M. Bieker, A. Königsrainer, W. Budach, H. Wilke Abstract 4511

25. Stahl M, et al. ASCO 2007. Abstract 4511 Patients with locally advanced esophagogastric adenocarcinoma Cisplatin 50 mg/m 2 Etoposide 80 mg/m 2 Radiation 30 Gy for 3 wks Arm A (N = 60) Arm B (N = 60) Cisplatin 50 mg/m 2 Folinic Acid 500 mg/m 2 5-FU 2 g/m 2 for 2.5 courses Cisplatin 50 mg/m 2 Folinic Acid 500 mg/m 2 5-FU 2 g/m 2 for 2 courses Trial Design

26. Results at Surgery CTX (N = 59) CRTX (N = 60) Patients with S88.1 %81.7 % R0-resection69.5 %71.7 % R1/R213.6 %3.3 % Exploration (N)34 Peritoneal mets. 2 Unresected 1 Peritoneal mets. 3 Hepatic mets. 1 Stahl M, et al. ASCO 2007. Abstract 4511

27. Pathohistologic Results CTX (N = 49) CRTX (N = 45) P T0N0M02.0 %15.6 %0.03 T1-4N0M034.7 %48.9 % T0-4N0M036.7 %64.4 %0.01 T0-4N+M055.1 %31.1 % T0-4N+M18.2 %4.4 % Stahl M, et al. ASCO 2007. Abstract 4511

28. Mortality After Surgery CTX (N = 52) CRTX (N = 49) Hospital mortality2 (3.8 %)5 (10.2 %) Pneumonia12 Anastom. leakage12 Cardiac shock01 Fisher’s exact P = 0.26 Stahl M, et al. ASCO 2007. Abstract 4511

29. Overall Survival Log rank P =.07 HR arm B vs. A: 0.67 (0.41-1.07) Follow-up: 45.6 mos Stahl M, et al. ASCO 2007. Abstract 4511 Years Survival Distribution Function 0 0.25 0.50 0.75 1.00 0135246 CRTX CTX27.7% 47.4%

30. Freedom from Local Tumor Progression Log rank P = 0.06 HR arm B vs. A: 0.45 (0.19 - 1.05) Years Survival Distribution Function 0 0.25 0.50 0.75 1.00 0135246 CRTX CTX 76.5% 59.0% Stahl M, et al. ASCO 2007. Abstract 4511

31. Preop Chemo vs. Preop Chemo RT Preop Chemo and Preop Chemo RT are feasible No difference in rate of R0 resection, + RT Higher post op mortality, + RT in multi institution trial Strong trend favoring improved OS, + RT –20% at 3 years (P = 0.07) Strong trend favoring improved local PFS, + RT –18% at 3 years (P = 0.06) Stahl M, et al. ASCO 2007. Abstract 4511

32. Preop Chemo vs. Preop Chemo RT Cannot conclude that the addition of RT improves outcome –Trial underpowered for primary endpoint Further trials of pre and post op chemo ± RT are warranted Netherlands: CRITICS Trial –Preop ECX  Surgery  –Post op chemo ± RT Korea: –Preop Capecitabine + Cisplatin  Surgery  –Cape/Cis ± RT Stahl M, et al. ASCO 2007. Abstract 4511

33. Gastric/Esophageal Cancer: Current Therapy Gastric Cancer: –Metastatic: 5-FU + cisplatin, RR of 20%, Med S 8-9 mos »Epirubicin (ECF), docetaxel + CF (DCF): 35-40% RR, med survival 9 mos »Capecitabine, oxaliplatin = CIV 5-FU, cisplatin

34. Gastric Cancer Chemotherapy: What Regimen to Use? Docetaxel + CF > CF: toxicity Irinotecan + CIV 5-FU = CF: less toxicity Oxaliplatin + Capecitabine: non inferior Doublets:Platin: + Irinotecan or Taxane or Fluor Flour: + Irinotecan or Taxane or Platin Oxaliplatin EOX or EOF Cape ECX or EOX XPFLOFUFIRIDCFECF Pts489513160109170221126 %,RR44%45%41%34%32%36%45% TTP, mos-- 5.65.55.05.6NS OS, mos10.910.410.5--9.09.28.9

35. Case 2: GE Junction Adenocarcinoma A 50-year-old man presents with increasing solid food dysphagia and a 20 pound weight loss. EGD reveals a GE junction mass with a biopsy revealing adenocarcinoma. A CT scan reveals multiple hepatic mets, lung and adrenal mets. Past history is only noted for asthma. PS 0. CT Scan PET Scan

36. Case 2: GE Junction Adenocarcinoma Which treatment option would you recommend?  Single agent 5-FU or capecitabine  5-FU/Cisplatin or FOLFOX  ECF, ECX, or EOX  DCF: Docetaxel, 5-FU, Cisplatin  FOLFIRI  Irinotecan + Cisplatin

37. Case 2: GE Junction Adenocarcinoma Phase III trials indicate that ECF is superior to FAMTX, and that DCF is superior to CF The patient was treated on a phase II trial of modified DCF –Docetaxel 40 mg/m 2 day 1 –Bolus 5-FU 400 mg/m 2, Leucovorin 400 mg/m 2 day 1, followed by 5-FU 1000 mg/m 2 /day x 2 days –Cisplatin 40 mg/m 2 day 3 –Cycled every 2 weeks –+ Bevacizumab 10 mg/kg day 1 Scans every 6 weeks showed progressive response, dysphagia resolved, PET scan normalized in the liver Dose reductions of 5-FU and docetaxel for mucositis No significant neutropenia or diarrhea Patient continues on therapy at 6 months

38. Case 2: GE Junction Adenocarcinoma CT Scan 2 CT Scan 1 PET Scan 2PET Scan 1

39. Gastric / Esophageal Cancer Abstracts: ASCO 2007 Metastatic disease: gastric cancer –S-1 vs. S-1 + Irinotecan –S-1 vs. 5-FU vs. 5-FU/Cisplatin –S-1 vs. S-1/Cisplatin –DCF vs. Docetaxel + Capecitabine

40. S-1 S-1: novel oral fluorouracil formulation FT: Tegafur, 5-FU prodrug + CDHP: DPD inhibitor + Oxo: bowel protectant Molar ratio of 1.0: 0.4: 1.0 Developed as orally absorbed 5-FU preparation with potentially less bowel toxicity

41. S-1 CDHP: inhibits DPD, which degrades 5-FU –180-fold higher DPD inhibitory activity than Uracil A high blood level of 5-FU retained when CDHP is combined with FT CDHP enhances oral FT uptake by blocking degradation by DPD in the bowel

42. S-1 Oxo: orotate phosphoribosyltransferase inhibitor Oxo: inhibits conversion of FT to FU in the bowel Reducing GI toxicity

43. S-1: Mechanism of Action

44. Irinotecan Plus S-1 (IRIS) Versus S-1 Alone as First-line Treatment for Advanced Gastric Cancer: Preliminary Results of a Randomized Phase III Study S-1 vs. S-1 + Irinotecan –326 pts –RR 27% vs. 42% (P = 0.035) –Grade 3/4 neutropenia: 9% vs. 27% –Grade 3/4 diarrhea: 6% vs. 16% –OS pending (powered to detect 3.5 mos inc OS) Chin K, et al. ASCO 2007. Abstract 4525

45. Randomized Phase III Study of 5-fluorouracil (5-FU) Alone Versus Combination of Irinotecan and Cisplatin (CP) Versus S-1 Alone In Advanced Gastric Cancer (JCOG9912) S-1 vs. CIV 5-FU vs. irinotecan/cisplatin 704 pts, primary endpoint irinotecan arm: increase 1-yr OS by 10% –Grade 3/4 neutropenia, nausea, diarrhea »65% for IC vs. 1-5% for S-1 or 5-FU »21% for IC vs. 0-1% for S-1 or 5-FU »9% for IC vs. 1-8% for S-1 or 5-FU –RR:IC: 38%5-FU: 9%S-1: 28% –PFS: 4.8 mos2.9 mos4.2 mos –OS12.3 mos10.8 mos11.4 mos Irinotecan/cisplatin and S-1 are superior to 5-FU, S-1 single agent approaches combination therapy activity Boku, et al. ASCO 2007. Abstract LBA4513

46. Randomized Phase III Study of S-1 Alone Versus S-1 + Cisplatin In the Treatment for Advanced Gastric Cancer (The SPIRITS trial) SPIRITS S-1 vs. S-1 + Cisplatin S-1 40-60 mg BID x 3 weeks alone, vs. S-1 + Cisplatin 60 mg/m 2 day 8, 2 weeks rest Primary endpoint OS: 8 mos  12 mos, 284 pts S-1: Active single agent, superior to CIV 5-FU alone Combination + cisplatin superior S-1 + Cisplatin a new standard in Japan FLAGS: Western trial of 5-FU vs. S-1 + Cisplatin S-1 S-1 + Cisplatin P Number150148 RR31%54%0.0018 OS 11 mos 13 mos0.0366 1-year47%54% 2-year15%24% PFS4 mos6 mos0.0089 Grade 3/4 Neut 11%40% Grae 3/4 Diarrhea 3% Grade 3/4 Nausea 1%12% Narahara et al. ASCO 2007. Abstract 4514

47. Weekly Docetaxel-based Chemotherapy Combinations in Advanced Esophago-gastric Cancer DCF in gastric cancer: 35% RR, TTP 5.6 mos, OS 9.2 mos –82% grade 3/4 neut., 30% neut. fever, 20% diarr and stomatitis Phase II: –DCF: Doc 30 mg/m 2 day 1 and 8, 5-FU 200 mg/m 2 /day x 21 days, Cisplatin 60 mg/m 2 day 1 vs. –DX: Doc 30 mg/m 2 day 1 and 8, Cape 1200 mg/m 2 /day x 14 days DCFDX 5056 RR49%26% Febrile Neutro 4%2% Gr 3/4 Diar 10%7% Gr 3/4 Stomat 22%2% PFS5.9 mos4.2 mos OS12.8 mos10.1 mos Tebbutt et al. ASCO 2007. Abstract 4528

48. Challenging Cases in Cancer: Integration of Findings from ASCO 2007 Pancreatic Cancer

49. Pancreatic Cancer: Current Therapy Primary Disease: Surgical Resection: –Only curative option »<20-30% operable »5 yr survival 0-20% –Adjuvant: »Chemo + RT: post op 5-FU/XRT (U.S) »Chemo Alone: 5-FU + leucovorin (Europe, ESPAC trial), or Gemcitabine alone (Europe, CONKO trial) Metastatic Disease: –Gemcitabine 1000 mg/m 2 /wk, 30 minute infusion »RR 6%, median survival 5.6 mos, 1-yr survival 18% –Gem + second drug: negative phase III trials for 5-FU, cisplatin, irinotecan, oxaliplatin, capecitabine –Gem + Erlotinib increases 1-year survival –ECOG: Gemcitabine FDR = Gemcitabine FDR + Oxaliplatin (10% RR, med. Surv. 6 months)

50. Case 3: Pancreatic Adenocarcinoma A 56 year old man with worsening diabetic control presents with abdominal pain and a 20 pound weight loss A CT scan reveals a pancreatic mass and innumerable hepatic metastases, Liver biopsy reveals pancreatic adenocarcinoma Past history is notable for now insulin dependent diabetes, hypertension, peptic ulcer disease and hypercholesterolemia. PS is 0

51. Case 3: Pancreatic Adenocarcinoma Which treatment option would you recommend?  Gemcitabine  Gemcitabine by fixed dose rate infusion  Gemcitabine + erlotinib  Gemcitabine + capecitabine  Gemcitabine + cisplatin/oxaliplatin

52. Case 3: Pancreatic Adenocarcinoma The patient was treated with gemcitabine (FDR) and oxaliplatin every 2 weeks. His CT scans showed substantial response and he gained weight. After 4 months doses were reduced due to thrombocytopenia. Erlotinib was added at 6 months Oxaliplatin was reduced to every 3 rd cycle at 8 months, although neuropathy remains grade 1. The patient continues on therapy at 22 months.

53. Case 3: Pancreatic Adenocarcinoma CT BaselineCT 3 months CT 22 months

54. Pancreatic Cancer Abstracts: ASCO 2007 Metastatic Disease, Phase III –Meta Analysis: gemcitabine vs. gem combination chemo –Second Line: 5-FU vs. 5-FU/oxaliplatin –SWOG S0205: gemcitabine ± cetuximab –CALGB 80303: gemcitabine ± bevacizumab

55. Gemcitabine vs. Gemcitabine + Another Drug? HR Survival P-ValueN Gem + platinum0.850.01623, 5 trials Gem + 5-FU0.900.03901, 6 trials Good PS 90%+ Poor PS 60- 80% 0.76 1.08 <0.0001 0.04 1,108, 5 trials 574 Patients with good performance status benefit from Gemcitabine combination chemotherapy: Gem + 5-FU/Cape, or Gem + platinum agent. For poor PS, single agent Gem ± erlotinib Heinemann, et al. ASCO 2007. Abstract 4515

56. CONKO-003 Phase III 5-FU+FA+Ox vs. 5-FU+FA, Second-line Primary endpoint: 2 month improvement in OS –Patients with POD on Gemcitabine Secondary: TTP, RR, toxicity N TTP (N = 145) OS (N = 130) 5-FU+FA+Ox76 12.3 weeks (10.9 – 123.7) 45 weeks (40.5 – 49.5) 5-FU+FA89 8 weeks (6.4- 9.5) 35.6 weeks (29.6 – 41.5) P > 0.05 Riess, et al. ASCO 2007. Abstract 4517

57. SWOG S0205: Study Schema Stratify Locally advanced vs. metastatic Prior pancreatectomy Yes vs. No Performance status 0/1 vs. 2 Gemcitabine + Cetuximab Gemcitabine + Cetuximab Gemcitabine RANDOMIZERANDOMIZE RANDOMIZERANDOMIZE Philip et al. ASCO 2007. Abstract LBA4509

58. S0205: Study Objectives Primary –Overall survival Secondary –Time to treatment failure –Objective response –Pain and quality of life (QoL) –Toxicity –EGFR expression and its correlation with outcome Philip et al. ASCO 2007. Abstract LBA4509

59. S0205: Patient Characteristics Gem + Cetux (N = 366) Gem (N = 369) Median Age (years)63.764.3 Female49%46% Performance Status 0/187% Locally Advanced21%22% Measurable Disease86.3%88.3% Prior Pancreatectomy10%11% Philip et al. ASCO 2007. Abstract LBA4509

60. S0205 Primary Endpoint: Survival of all Patients 5.9 6.4 HR = 1.09 (95% CI: 0.93, 1.27) Overall Survival by Treatment Arm 0% 20% 40% 60% 80% 100% 0122436 Months After Registration Gemcitabine Gemcitabine and Cetuximab N 369 366 Events 338 331 Median in Months P = 0.14 Philip et al. ASCO 2007. Abstract LBA4509

61. S0205: Progression-free Survival HR = 1.13 (95% CI: 0.97, 1.31) Progression-free Survival by Treatment Arm 0% 20% 40% 60% 80% 100% 0612182430 Months After Registration 3.0 3.5 Gemcitabine Gemcitabine and Cetuximab N 369 366 Events 360 351 Median in Months P = 0.058 Philip et al. ASCO 2007. Abstract LBA4509

62. S0205: Objective Tumor Response Response Gem + Cetux (%) (N = 316) Gem (%) (N = 326) CR01 PR1213 SD3830 CR + PR + SD5044 PD4047 Philip et al. ASCO 2007. Abstract LBA4509

63. Advanced Pancreatic Cancer N = 590 Gemcitabine Placebo Gemcitabine Bevacizumab Stratification: Performance status: 0/1 vs. 2 Extent of disease: metastatic vs. locally advanced Prior radiation: yes/no RANDOMIZERANDOMIZE CALGB 80303: Trial Design Kindler et al. ASCO 2007. Abstract 4508

64. CALGB 80303: Endpoints Primary Endpoint: Overall survival Secondary Endpoints: Objective response rate Duration of response Progression-free survival Toxicity Kindler et al. ASCO 2007. Abstract 4508

65. Patient Characteristics Characteristic Gemcitabine Bevacizumab (N = 302) Gemcitabine Placebo (N = 300) Median age (years)63.865.0 Male Female 58% 42% 51% 49% Performance status 0 1 2 36% 53% 11% 39% 52% 9% Locally advanced Metastatic 15% 85% 16% 84% Prior radiation11% Kindler et al. ASCO 2007. Abstract 4508

66. CALGB 80303: Objective Response Gemcitabine Bevacizumab Gemcitabine Placebo Complete Response 1%2% Partial Response 10%8% Stable Disease 36%31% Disease Control: CR + PR + SD 47%40% Kindler et al. ASCO 2007. Abstract 4508

67. CALGB 80303: Progression-free Survival by Treatment Arm HR=1.00 p=0.99 Bevacizumab 4.9 mos Placebo 4.7 mos HR = 1.00 P = 0.99 Kindler et al. ASCO 2007. Abstract 4508

68. CALGB 80303: Overall Survival by Treatment Arm Bevacizumab 5.8 mos Placebo 6.1 mos HR = 1.03 P = 0.78 Kindler et al. ASCO 2007. Abstract 4508

69. Conclusions Preoperative chemotherapy and preoperative chemoradiotherapy for adjuvant treatment of GE junction adenocarcinoma Potential benefit with the addition of radiation to preoperative chemotherapy with improvements in overall survival and local disease control Advanced metastatic gastric cancer – new oral drug S1 has promising activity as a single agent and significant activity in combination with either irinotecan or cisplatin Modified DCF regimen has improved toxicity profile in the treatment of advanced metastatic gastric cancer Important meta-analysis indicates gemcitabine combination therapy with either a 5-FU or a platinum agent maybe used in pancreatic cancer patients with good performance status