Medical treatment of  pancreatic cancer UVSQ University  of Versailles Saint Quentin  en yveline Philippe Rougier Digestiv...
Pancreatic cancer: a major  therapeutic challenge <ul><li>Pancreatic cancer is a fatal disease </li></ul><ul><ul><li>fourt...
Medical treatment of metastatic pancreatic cancer <ul><li>Metastatic PC  </li></ul><ul><ul><li>Past history of chemotherap...
1997: Gemcitabine became a standard of care in advanced pancreatic cancer 0 2 4 6 8 10 12 14 16 18 20 100 80 60 40 20 0 We...
Heinemann V, BMC Cancer 2008  Platin salts Fluoropyrimidines Autres in favor of Gem + X in favor of Gem alone Meta-analysi...
Medical treatment of metastatic pancreatic cancer <ul><li>Metastatic PC  </li></ul><ul><ul><li>Past history of chemotherap...
PRODIGE 4 / Accord 11 trial  Phase III : Gemzar  vs  Folfirinox <ul><li>T. Conroy  et al .,  ASCO 2010, A 4010 ; N Engl J ...
Disease characteristics T. Conroy  et al .,  ASCO 2010, A 4010 ; N Engl J Med 2011 in press Characteristic Folfirinox N=17...
Safety: hematological adverse events (Aes) 5.4 42.5% of the pts received G-CSF in the F arm vs 5.3% in the G arm One toxic...
Objective Response Rate T. Conroy  et al .,  ASCO 2010, A 4010 ; N Engl J Med 2011 in press Folfirinox N=171 Gemcitabine N...
Progression-Free Survival Median PFS Folfirinox: 6.4 mo.   Median PFS Gemcitabine: 3.3 mo HR (95% CI): 0.47 (0.37-0.59) ; ...
Overall Survival T. Conroy  et al .,  ASCO 2010, A 4010 ; N Engl J Med 2011 in press Median survival [CI 95%]:  11.1 mo .[...
Time to definitive QoL degradation  T. Conroy  et al .,  ASCO 2010, A 4010 ; N Engl J Med 2011 in press
Conclusions <ul><li>Folfirinox  more toxic but  … with manageable toxicity  => higher rate of gr. 3/4 febrile neutropenia ...
Medical treatment of metastatic pancreatic cancer <ul><li>Metastatic PC  </li></ul><ul><ul><li>Past history of chemotherap...
Combining gemcitabine with  biological therapies <ul><li>Gemcitabine +  Marimastat   Bramhall, Br J Cancer 2002 </li></ul>...
PA.3: Overall Survival in  metastatic pancreatic cancer 1.00 0.75 0.50 0.25 0 0 6 12 18 24 30 36 Time (months) Gemcitabine...
Conatumumab / AMG 479, phase II in Metastatic Pancreatic Cancer …  phase III in progress Patients à risque H. L. Kindler  ...
Pancreatic cancer: recent progress ? <ul><li>Past history of chemotherapy </li></ul><ul><li>New active regimens ? </li></u...
Clinical trials investigating second-line chemotherapy in gemcitabine-pretreated pts with advanced pancreatic cancer c c T...
5FU- Folinic-Ac (FF) Oxaliplatin-5FU- Folinic-Ac (OFF) non resecable Cancer (Localy avanced or Metastatic) Progression und...
<ul><li>Overall survival </li></ul><ul><li>Primary endpoint of the study </li></ul>Progression free-survival FFCD 0301:  s...
Recommendations for second line tt <ul><li>Increased Nb of patients treaited in  2 nd  line  </li></ul><ul><li>no robust d...
Medical treatment of metastatic pancreatic cancer <ul><li>Metastatic PC  </li></ul><ul><ul><li>Past history of chemotherap...
venous thromboembolic event : VTE Advanced pancreatic adenocarcinoma :  CONKO 004 trial  Efficacy of preventive anticoagul...
<ul><li>FUTURE ? </li></ul><ul><li>Better selection of patients: </li></ul><ul><li>Predictive factors for response to Gemc...
Gemcitabine:  mechanism of action Human equilibrative nucleoside transporter 1 (hENT1) Human concentrative nucleoside tran...
<ul><li>OS Median: </li></ul><ul><li>-2 factors: not reached </li></ul><ul><li>1 factor: 18.7 months </li></ul><ul><li>0 f...
CDA: enzyme of gemcitabine   catabolism cytidine deaminase (CDA) enzymatic activity and toxicity/efficacy of gemcitabine (...
Adjuvant treatment of pancreatic cancer <ul><li>surgery </li></ul><ul><li>Chemo-radiotherapy RTCT ? </li></ul><ul><li>Chem...
In absence of metastase and local infiltration: Whipple = Cephalic Duodeno Pancreatectomy
non-resecability criteria  <ul><li>R1 or R2 CDP is contre-indicated: </li></ul><ul><ul><li>No long term survival & 5% risk...
Stenting in case of icterus in non resectable case or metastses
Quality of Pathological exam +++
Medical treatment of metastatic pancreatic cancer <ul><li>Metastatic PC  </li></ul><ul><ul><li>Past history of chemotherap...
9 m vs 11 m p = 0,01 11 m vs 20 m p = 0,03
<ul><li>Feb 1994- June 2000 </li></ul><ul><li>11 countriess </li></ul><ul><li>237 DC/ 289 patients </li></ul><ul><li>Media...
ESPAC1: Chemotherapy  vs   No chemotherapy : Survival at 5 years  21% vs 8% (p = 0.009)
DFS : 13.4  vs   6.9 m p < 0.001 Overall survival : 22.1  vs   20.2 m p < 0.06   CONKO-001:adjuvant Gemcitabine ?
Neoptolemos J, ASCO 2009, LBA4505 = No  difference ESPAC 3 (V2): FU/FA or Gem ? Survival ESPAC 3 (V2): Toxicity Grade 3-4 ...
SYNTHESIS:  MEDICAL TREATMENTS IN PANCREATIC CANCER IN 2011: METASTASES (1) <ul><li>Gemcitabine  is still a standard ( gra...
<ul><li>Second line chemotherapy  may be offer in patients in with good prognostic factors  </li></ul><ul><ul><ul><li>- FO...
<ul><li>Chemotherapy  is more efficient than combined radiochemotherapy after R0 resection. </li></ul><ul><li>Gemcitabine ...
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MCO 2011 - Slide 23 - P. Rougier - Gastric and pancreatic cancers (part II)

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MCO 2011 - Slide 23 - P. Rougier - Gastric and pancreatic cancers (part II)

  1. 1. Medical treatment of pancreatic cancer UVSQ University of Versailles Saint Quentin en yveline Philippe Rougier Digestive Oncology Hopital Européen Georges Pompidou 75015 Paris ; France [email_address] Pancreas: A complex anatomy
  2. 2. Pancreatic cancer: a major therapeutic challenge <ul><li>Pancreatic cancer is a fatal disease </li></ul><ul><ul><li>fourth/fifth-leading cause of cancer-related deaths </li></ul></ul><ul><ul><li>overall survival is amongst the shortest of any solid tumour </li></ul></ul><ul><li>Treatment options are limited …. </li></ul>1 Burris H, et al. J Clin Oncol 1997;15:2403 – 13
  3. 3. Medical treatment of metastatic pancreatic cancer <ul><li>Metastatic PC </li></ul><ul><ul><li>Past history of chemotherapy </li></ul></ul><ul><ul><li>New active regimens ? </li></ul></ul><ul><ul><li>Targeted therapy </li></ul></ul><ul><ul><li>Second line treatments </li></ul></ul><ul><ul><li>Prevention of vascular complications </li></ul></ul><ul><li>Adjuvant TT </li></ul><ul><ul><li>Radiochemotherapy </li></ul></ul><ul><ul><li>chemotherapy </li></ul></ul>
  4. 4. 1997: Gemcitabine became a standard of care in advanced pancreatic cancer 0 2 4 6 8 10 12 14 16 18 20 100 80 60 40 20 0 Weekly b 5-FU Weekly Gemcitabine Survival time (months) Patients surviving (%) 1 Burris H, et al. J Clin Oncol 1997;15:2403 – 13 Gemcitabine 5-FU p Median survival (mo) 5.65 4.41 0.0025 Clinical benefit (%) 23.8 4.8 0.0022 1-year survival (%) 18 2
  5. 5. Heinemann V, BMC Cancer 2008 Platin salts Fluoropyrimidines Autres in favor of Gem + X in favor of Gem alone Meta-analysis: combinations in first line Not done on individal data G + Platinum salts G + FU derivatives
  6. 6. Medical treatment of metastatic pancreatic cancer <ul><li>Metastatic PC </li></ul><ul><ul><li>Past history of chemotherapy </li></ul></ul><ul><ul><li>New active regimens ? </li></ul></ul><ul><ul><li>Targeted therapy </li></ul></ul><ul><ul><li>Second line treatments </li></ul></ul><ul><ul><li>Prevention of vascular complications </li></ul></ul><ul><li>Adjuvant TT </li></ul><ul><ul><li>Radiochemotherapy </li></ul></ul><ul><ul><li>chemotherapy </li></ul></ul>
  7. 7. PRODIGE 4 / Accord 11 trial Phase III : Gemzar vs Folfirinox <ul><li>T. Conroy et al ., ASCO 2010, A 4010 ; N Engl J Med 2011 in press </li></ul>GEMZAR (Burris) FOLFIRINOX* primary endpoint : OS Gain : 7 to 10 months ADK pancreas M+ N = 342 Stratification : center PS : 0 vs 1 head vs other localisation 6 months of chemotherapy recommended CTscan every 2 months In each arm : R * Folfirinox : d1 = d14 - Oxaliplatin 85mg/m 2 d1 - Irinotecan 180mg/m 2 d1 - folinic acid 400mg/m 2 d1 - 5FU 2400 mg/m 2 / d1-2
  8. 8. Disease characteristics T. Conroy et al ., ASCO 2010, A 4010 ; N Engl J Med 2011 in press Characteristic Folfirinox N=171 Gemcitabine N=171 p Synchronous metastases Metachronous metastases 156 (91.2%) 15 (8.8%) 161 (94.2%) 10 (5.8%) NS NS Median nr. of T sites CA19-9  59 ULN 2 (1-6) 68 (41.5%) 2 (1-6) 77 (46.7%) NS NS Measurable site Liver Pancreas Nodes Lungs Peritoneal 149 (88.2%) 89 (52.7%) 48 (28.4%) 33 (19.5%) 33 (19.5%) 150 (87.7%) 91 (53.2%) 39 (22.8%) 49 (28.7%) 32 (18.7%) NS NS NS 0.049 NS
  9. 9. Safety: hematological adverse events (Aes) 5.4 42.5% of the pts received G-CSF in the F arm vs 5.3% in the G arm One toxic death occurred in each arm T. Conroy et al ., ASCO 2010, A 4010 ; N Engl J Med 2011 in press AE, % per patient Folfirinox N=167 Gemcitabine N=169 p All Grade 3/4 All Grade 3/4 Grade 3/4 Neutropenia 79.9 45.7 54.8 18.7 0.0001 Febrile Neutropenia 7.2 2.4 0.6 0.009 Anemia 90.4 7.8 94.6 5.4 NS Thrombocytopen. 75.2 9.1 54.8 2.4 0.008
  10. 10. Objective Response Rate T. Conroy et al ., ASCO 2010, A 4010 ; N Engl J Med 2011 in press Folfirinox N=171 Gemcitabine N=171 p Complete response 0.6% 0% Partial response 31% 9.4% 0.0001 CR/PR 95% CI [24.7-39.1] [5.9-15.4] Stable disease 38.6% 41.5% Disease control CR+PR+SD 70.2% 50.9% 0.0003 Progression 15.2% 34.5% Not assessed 14.6% 14.6% Median duration of response 5.9 mo. 4 mo. ns
  11. 11. Progression-Free Survival Median PFS Folfirinox: 6.4 mo. Median PFS Gemcitabine: 3.3 mo HR (95% CI): 0.47 (0.37-0.59) ; p < 0.0001 T. Conroy et al ., ASCO 2010, A 4010 ; N Engl J Med 2011 in press
  12. 12. Overall Survival T. Conroy et al ., ASCO 2010, A 4010 ; N Engl J Med 2011 in press Median survival [CI 95%]: 11.1 mo .[ 9 - 13.1] vs 6.8 mo .[ 5.5 - 7.6] P = <0.0001 ; HR = 0.57 [0.45 – 0.73]
  13. 13. Time to definitive QoL degradation T. Conroy et al ., ASCO 2010, A 4010 ; N Engl J Med 2011 in press
  14. 14. Conclusions <ul><li>Folfirinox more toxic but … with manageable toxicity => higher rate of gr. 3/4 febrile neutropenia (5.4%) => vigilant pt selection, education, monitoring, management </li></ul><ul><li>Folfirinox regimen is an efficient outpatient schedule : </li></ul><ul><ul><li>Significantly improves PFS </li></ul></ul><ul><ul><li>Delays QoL degradation </li></ul></ul><ul><ul><li>Significantly improves overall survival (HR 0.57, p<0.0001) => + 4.3 mths compared to gemcitabine alone. </li></ul></ul><ul><ul><li>Folfirinox is a new standard of care for patients with metastatic pancreatic cancer, bilirubin <1.5 UNL and PS 0-1 in France (“tncd.org) </li></ul></ul><ul><li>Folfirinox will be tested in other indications (adjuvant, neoadjuvant …) </li></ul>T. Conroy et al ., ASCO 2010, A 4010 ; N Engl J Med 2011 in press
  15. 15. Medical treatment of metastatic pancreatic cancer <ul><li>Metastatic PC </li></ul><ul><ul><li>Past history of chemotherapy </li></ul></ul><ul><ul><li>New active regimens ? </li></ul></ul><ul><ul><li>Targeted therapy </li></ul></ul><ul><ul><li>Second line treatments </li></ul></ul><ul><ul><li>Prevention of vascular complications </li></ul></ul><ul><li>Adjuvant TT </li></ul><ul><ul><li>Radiochemotherapy </li></ul></ul><ul><ul><li>chemotherapy </li></ul></ul>
  16. 16. Combining gemcitabine with biological therapies <ul><li>Gemcitabine + Marimastat Bramhall, Br J Cancer 2002 </li></ul><ul><li>Gemcitabine + Tipifarnib van Cutsem, JCO 2004 </li></ul><ul><li>Gemcitabine + Cetuximab Philip, ASCO 2007 </li></ul><ul><li>Gemcitabine + Bevacizumab Kindler, ASCO 2007 </li></ul><ul><li>Gemcitabine + Tarceva Moore, JCO 2007 </li></ul>
  17. 17. PA.3: Overall Survival in metastatic pancreatic cancer 1.00 0.75 0.50 0.25 0 0 6 12 18 24 30 36 Time (months) Gemcitabine + Tarceva Gemcitabine + placebo Survival probability HR=0.80 (0.66–0.98); p=0.029 Led to EU approval for the treatment of metastatic pancreatic cancer <ul><li>Erlotinib (Tarceva R ) improves OS </li></ul><ul><li>only in case of skin reaction ? Is it clinically meaningful ? </li></ul>Moore, JCO 2007 Gemcitabine + Tarceva Gemcitabine + placebo n 200 197 Median survival, months 5.93 5.06
  18. 18. Conatumumab / AMG 479, phase II in Metastatic Pancreatic Cancer … phase III in progress Patients à risque H. L. Kindler et al ., ASCO 2010, A 4035 Trend in favor of anti IGFR efficacy ? Events Median OS (95% CI), mthis HR (95% CI) a p Conatumumab + gemcitabine 32 (78%) 7.5 (4.8, 10.0) 0.87 (0.53, 1.43) 0.59 AMG 479 + gemcitabine 29 (69%) 8.7 (5.3, 12.2) 0.67 (0.41, 1.12) 0.12 Placebo + gemcitabine 34 (81%) 5.9 (4.1, 9.7) 41 39 38 33 29 25 23 23 19 14 14 11 7 5 3 1 0 0 0 0 0 0 0 0 0 42 39 37 34 30 28 22 21 20 17 17 15 13 8 6 6 4 3 3 3 2 1 1 1 0 42 39 38 30 26 20 19 16 15 14 13 12 6 3 2 2 1 1 1 1 0 0 0 0 0 0.0 0.2 0.4 0.6 0.8 1.0 Survie globale 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 Mois
  19. 19. Pancreatic cancer: recent progress ? <ul><li>Past history of chemotherapy </li></ul><ul><li>New active regimens ? </li></ul><ul><li>Targeted therapy </li></ul><ul><li>Second line treatments </li></ul><ul><li>Prevention of vascular complications </li></ul>
  20. 20. Clinical trials investigating second-line chemotherapy in gemcitabine-pretreated pts with advanced pancreatic cancer c c Treatment regimen No. of patients KPS 90-100% / ECOG 0-1 Metastatic disease (%) RR (%) DCR (%) PFS/TTP (months) OS (months) Oxa/5-FU CI/LV vs BSC 46 NA NA NA NA OFF:5.25 BSC:2.5 OFF:10 BSC:8.5 Oxa/5-FU CI/LV vs 5-FU CI/LV (nb = 168) OFF:77 FF: 91 OFF:54% FF: 50 % OFF:85.5 FF: 89.2 NA NA OFF:3.25 FF: 2.25 OFF:6.5 FF: 3.25 Oxa/5-FU CI/LV 30 33 % 97 23 53 5.1 5.8 FOLFOX-4 42 62 % 83 14 52 4 6.7 Modified FOLFOX 30 97 % NA NA 20 1.4 4 vs modified FOLFIRI 30 100 % 28 1.9 4 Oxa + Gem 33 88 % 64 21 58 4.2 6.0 Oxa + Cap 39 80 % NA 3 23 NA 5.8 Oxa + irinotecan 30 30 % 100 10 33 4.1 5.9 Oxa + raltitrexed 41 61 % 100 24 51 1.8 5.2 Cisplatin + irinotecan + Gem + 5-FU + LV 34 NA 100 24 44 3.9 10.3 Cap + Gem + docetaxel 35 52 100 29 60 NA 11.2
  21. 21. 5FU- Folinic-Ac (FF) Oxaliplatin-5FU- Folinic-Ac (OFF) non resecable Cancer (Localy avanced or Metastatic) Progression under Gem Karnowsky >60 n=165 Pelzer et al, ASCO 2008 A 4508 FF : 5FU 2000 mg/m²/24h, ac. folinic 200 mg/m² in 30 mn D1- D 8- D 15- D 22 OFF : FF + Oxaliplatin 85 mg/m² D 8- D 22 D 1= D 43 Primary endpoint : Overall Survival Second line chemotherapy: CONKO-3 trial R Per protocol FF OFF p PFS (weeks) 9 13 0.012 Overall Survival (weeks) 13 26 0.014
  22. 22. <ul><li>Overall survival </li></ul><ul><li>Primary endpoint of the study </li></ul>Progression free-survival FFCD 0301: strategic trial: which 1rst line and 2d line ? ARM A FUP -> Gem ARM B Gem -> FUP P (log-rank) Median mths [95% CI] 6.63 [5.27 – 8.07] 8.03 [5.93 – 9.97] 0.77 ARM A ARM B P Median mths [95% CI] 3.83 [2.36 – 7.03] 4.73 [2.43-8.23] 0.9
  23. 23. Recommendations for second line tt <ul><li>Increased Nb of patients treaited in 2 nd line </li></ul><ul><li>no robust data ; phase III needed </li></ul><ul><li>Fluoropyrimidines : interest if PS > 1 </li></ul><ul><li>Combinaisons : if PS 0-1 </li></ul><ul><ul><li>OFF or FOLFOX are a « standard » (randomised trial) </li></ul></ul><ul><ul><li>What about Capox / GEMOX or CDDP or FOLFIRI ? </li></ul></ul><ul><ul><li>Capecitabine + erlotinib ? </li></ul></ul><ul><li>Pronostic & predictive Factors needed </li></ul>
  24. 24. Medical treatment of metastatic pancreatic cancer <ul><li>Metastatic PC </li></ul><ul><ul><li>Past history of chemotherapy </li></ul></ul><ul><ul><li>New active regimens ? </li></ul></ul><ul><ul><li>Targeted therapy </li></ul></ul><ul><ul><li>Second line treatments </li></ul></ul><ul><ul><li>Prevention of vascular complications </li></ul></ul><ul><li>Adjuvant TT </li></ul><ul><ul><li>Radiochemotherapy </li></ul></ul><ul><ul><li>chemotherapy </li></ul></ul>
  25. 25. venous thromboembolic event : VTE Advanced pancreatic adenocarcinoma : CONKO 004 trial Efficacy of preventive anticoagulation ? LMWH decreases the risk of VTES But does not influence significantly the OS H. Riess et al ., ASCO 2010, , A 4033 énoxaparine (Lovenox ® ) 1 mg/kg/j for 3 months then 40 mg/j N = 312 CT N = 152 CT + enoxaparine N = 160 p VTE at 3 months 9,9 % 1,25 % < 0,01 VTE at 12 months 15% 5% severes haemorragic Complications   ns TTP 5.4 months 5 months P = 0.94 Overall Survival 8 months 8.3 months P = 0.5
  26. 26. <ul><li>FUTURE ? </li></ul><ul><li>Better selection of patients: </li></ul><ul><li>Predictive factors for response to Gemcitabine </li></ul><ul><li>Predictive factors for toxicity to Gemcitabine </li></ul><ul><li>Better drugs and combinations ? </li></ul>
  27. 27. Gemcitabine: mechanism of action Human equilibrative nucleoside transporter 1 (hENT1) Human concentrative nucleoside transporter 1 (hCNT1) Human concentrative nucleoside transporter 3 (hCNT3) CDA: gemcitabine catabolism enzyme
  28. 28. <ul><li>OS Median: </li></ul><ul><li>-2 factors: not reached </li></ul><ul><li>1 factor: 18.7 months </li></ul><ul><li>0 factor: 12.2 months </li></ul>hENT1 low hENT1 elevated p OS PFS 13.3 months 8.4 months Not reached 46.8 months 0.0001 hCNT3 low hCNT3 elevated OS PFS 12.6 months 8.6 months Not reached 23.5 months 0.02
  29. 29. CDA: enzyme of gemcitabine catabolism cytidine deaminase (CDA) enzymatic activity and toxicity/efficacy of gemcitabine (?) ACTIVE METABOLITES 2’-dFdU (inactive) Cytidine Deaminase (CDA) gene polymorphism Gemzar ®
  30. 30. Adjuvant treatment of pancreatic cancer <ul><li>surgery </li></ul><ul><li>Chemo-radiotherapy RTCT ? </li></ul><ul><li>Chemotherapy ? </li></ul>
  31. 31. In absence of metastase and local infiltration: Whipple = Cephalic Duodeno Pancreatectomy
  32. 32. non-resecability criteria <ul><li>R1 or R2 CDP is contre-indicated: </li></ul><ul><ul><li>No long term survival & 5% risk of post-op death … </li></ul></ul><ul><li>Distant metastase </li></ul><ul><li>Local extension : </li></ul><ul><ul><ul><li>Mesenteric artery </li></ul></ul></ul><ul><ul><ul><li>Lymph nodes </li></ul></ul></ul><ul><ul><ul><li>peri-pancreatic tissue </li></ul></ul></ul><ul><ul><ul><li>veina cava or aorta </li></ul></ul></ul><ul><ul><ul><li>Portal vein thrombosis & occlusion of the superior mesenteric vein </li></ul></ul></ul>
  33. 33. Stenting in case of icterus in non resectable case or metastses
  34. 34. Quality of Pathological exam +++
  35. 35. Medical treatment of metastatic pancreatic cancer <ul><li>Metastatic PC </li></ul><ul><ul><li>Past history of chemotherapy </li></ul></ul><ul><ul><li>New active regimens ? </li></ul></ul><ul><ul><li>Targeted therapy </li></ul></ul><ul><ul><li>Second line treatments </li></ul></ul><ul><ul><li>Prevention of vascular complications </li></ul></ul><ul><li>Adjuvant TT </li></ul><ul><ul><li>Radiochemotherapy </li></ul></ul><ul><ul><li>chemotherapy </li></ul></ul>
  36. 36. 9 m vs 11 m p = 0,01 11 m vs 20 m p = 0,03
  37. 37. <ul><li>Feb 1994- June 2000 </li></ul><ul><li>11 countriess </li></ul><ul><li>237 DC/ 289 patients </li></ul><ul><li>Median follow-upi: 47 mois </li></ul>ESPAC 1: Radiochimiotherapy vs no radiochimiotherapy : 5 year’survival 10% vs 20% (p = 0.05 ) Neoptolemos JP, NEJM, 2004
  38. 38. ESPAC1: Chemotherapy vs No chemotherapy : Survival at 5 years 21% vs 8% (p = 0.009)
  39. 39. DFS : 13.4 vs 6.9 m p < 0.001 Overall survival : 22.1 vs 20.2 m p < 0.06 CONKO-001:adjuvant Gemcitabine ?
  40. 40. Neoptolemos J, ASCO 2009, LBA4505 = No difference ESPAC 3 (V2): FU/FA or Gem ? Survival ESPAC 3 (V2): Toxicity Grade 3-4 5-FU/AF Gemcitabine p Thrombopénie 0 % 1,5 % 0,0034 Mucite 10 % 0 % < 0,001 Diarrhée 13 % 2 % < 0,001
  41. 41. SYNTHESIS: MEDICAL TREATMENTS IN PANCREATIC CANCER IN 2011: METASTASES (1) <ul><li>Gemcitabine is still a standard ( grade A ): </li></ul><ul><ul><li>- hENT1 / 3 elevated ? </li></ul></ul><ul><ul><li>- non extensisve CDA ? </li></ul></ul><ul><li>Gemcitabine + erlotinib improves survival ( grade B ) </li></ul><ul><ul><li>- in selected patients ? (skin rashes) </li></ul></ul><ul><li>Combinations of Gemcitabine with capecitabine, platinum salts only marginally improve the efficacy ( when RR is concerned) ( grade B and experts opinion ) </li></ul><ul><li>FOLFIRINOX improve the OS in selected population. (PS: 0-1) and is a new standard ( grade A ) </li></ul>
  42. 42. <ul><li>Second line chemotherapy may be offer in patients in with good prognostic factors </li></ul><ul><ul><ul><li>- FOLFOX following Gem </li></ul></ul></ul><ul><ul><ul><li>- Gem following FOLFORINOX) ; </li></ul></ul></ul><ul><ul><ul><li>- Interest of addition of Erlotinib under investigation. </li></ul></ul></ul><ul><li>Biological markers for response, survival and toxicity must be developped and used to favor better therapeutic index +++. </li></ul>SYNTHESIS: MEDICAL TREATMENTS IN PANCREATIC CANCER IN 2011: METASTASES (2)
  43. 43. <ul><li>Chemotherapy is more efficient than combined radiochemotherapy after R0 resection. </li></ul><ul><li>Gemcitabine and 5FU/folinic acid improve survival </li></ul><ul><li>In the same range. </li></ul><ul><li>Radiochemotherapy using new schedule and after chemotherapy may improve survival and/or reduce the local recurrence rate. It is indicated in case of R1 or R2 resection. </li></ul>SYNTHESIS: MEDICAL TREATMENTS IN PANCREATIC CANCER IN 2011: ADJUVANT

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