PANCREATIC CANCER  A CHALLENGE FOR MODERN MEDICINE IN THE 21 ST  CENTURY
ETHIOLOGICAL FACTORS <ul><li>TOBACCO  2:1 </li></ul><ul><li>CRONIC PANCREATITIS  </li></ul><ul><li>OBESITY </li></ul><ul><...
 
 
 
 
EARLY SYMPTOMS Y SIGNS OF PANCREATIC CANCER <ul><li>COMMON  </li></ul><ul><ul><li>VISCERAL PAIN </li></ul></ul><ul><ul><li...
CASE 3 A 65 YEAR OLD WOMAN WITH UNRESECTABLE PANCREATIC CANCER <ul><li>DIABETES MELLITUS DIAGNOSED ONE YEAR AGO </li></ul>...
CASE 3 A 65 YEAR OLD WOMAN WITH UNRESECTABLE PANCREATIC CANCER <ul><li>PHYSICAL EXAMINATION: </li></ul><ul><ul><li>NO HEPA...
LABORATORY DATA IN  PANCREATIC CANCER <ul><li>NONE OF THE IS SPECIFIC </li></ul><ul><li>OBSTRUCTIVE JAUNDICE </li></ul><ul...
IMAGING FOR DIAGNOSIS AND STAGING  PANCREATIC CARCINOMA <ul><li>ABDOMINAL ULTRASONOGRAPHY </li></ul><ul><li>HELYCAL CT-SCA...
CASE 3 A 65 YEAR OLD WOMAN WITH UNRESECTABLE PANCREATIC CANCER <ul><li>LABORATORY DATA: </li></ul><ul><ul><li>No anemia  <...
CLINICAL STAGING OF PANCREATIC CANCER <ul><ul><li>RESECTABLE  </li></ul></ul><ul><ul><ul><li>T1-2 NX M0 </li></ul></ul></u...
 
 
 
 
 
 
 
 
 
 
 
<ul><li>CURE IS SOMEHOW EXCEPTIONAL </li></ul><ul><li>PALLIATIVE THERAPY </li></ul><ul><li>SYMPTOMS CONTROL </li></ul><ul>...
CASE 3 A 65 YEAR OLD WOMAN WITH UNRESECTABLE PANCREATIC CANCER <ul><li>Therapeutic plan </li></ul><ul><ul><li>Control pain...
CLINICAL   BENEFIT USE OF  ANALGESICS PAIN  INTENSITY  PAIN PERFORMANCE  STATUS RESPONSE STABLE NO  RESPONSE RESPONSE NO  ...
GEMCITABINE 5-FU NR PATIENTS 63 63 TIME TO  PROGRESSION p median 2.33 m .0002   0.92 m 6 months 22%  5% 12 months  9%  5% ...
  GEMCITABINE   5-FU Nr. Patients  63   63 Pain improvement   23.8%   4.8% Pain improvement With improved  or stable PS   ...
  GEMCITABINE   5-FU Nr. Patients  63   63 Pain improvement   23.8%   4.8% Pain improvement With improved  or stable PS   ...
STATHIS et al. Nat Rev Clin Oncol 2010
Heinemann V, et al  BMC Cancer 2008
Heinemann V, et al  BMC Cancer 2008
STATHIS et al. Nat Rev Clin Oncol 2010
 
 
Stratified by: - Center - PS (0/1 vs 2) - Stage of disease (locally advanced vs  distant metastases) RANDOM  I ZE Gemcitab...
GEMCITABINE +/- ERLOTINIB IN ADVANCED PANCREATIC CANCER :  Overall Survival
 
A MULTIDISCIPLINARY APPROACH IS  NEEDED TO TREAT PANCREATIC CANCER PANCREATIC CANCER IS RARELY CURED WITH SURGERY RESECTAB...
A MULTIDISCIPLINARY APPROACH FOR  PANCREATIC CANCER TREATMENT  PANCREATIC CANCER IS A A SYSTEMIC DISEASE ROLE OF ADJUVANT ...
Signal transduction pathways via Ras and PI3K/Akt that cause cell proliferation and survival ■  EGFR ■  IGF‑1R ■  HGFR ■  ...
<ul><li>THE ABILITY TO UNDERGO SELF RENEWAL </li></ul><ul><li>THE DEVELOPMENTAL POTENTIAL TO RECAPITULATE ALL THE CELL TYP...
THE CANCER STEM CELL HYPOTHESIS: THERAPEUTIC STRATEGIES TO TARGET TUMOUR-INITIATING CELLS Sergeant G., et al Nature Rev Cl...
THE CANCER STEM CELL HYPOTHESIS: THERAPEUTIC STRATEGIES TO TARGET TUMOUR-INITIATING CELLS Zhou BS. Nature Rev Drug Discov ...
THE CANCER STEM CELL HYPOTHESIS: THERAPEUTIC STRATEGIES TO TARGET TUMOUR-INITIATING CELLS Zhou BS. Nature Rev Drug Discov ...
A MULTIDISCIPLINARY APPROACH IS  NEEDED TO TREAT PANCREATIC CANCER PANCREATIC CANCER IS RARELY CURED WITH SURGERY RESECTAB...
Adjuvant treatment in resected Pancreatic Cancer ESPAC-1 <ul><li>Pancreatic or ampullary adenocarcinoma, R0 or R1 </li></u...
Survival rates  2-year 5-year No CRT: 41.4% 19.6% CRT: 28.5% 10.0% HR=1.28 (0.99, 1.66), p=0.053 ESPAC-1 NEJM  2004 ; 350:...
Survival rates 2-year 5-year No CT: 30.0% 8.4% CT: 39.7% 21.1% HR=0.71 (0.55, 0.92), p=0.009 ESPAC-1 NEJM 2004; 350:1200-1...
Adjuvant treatment in resected Pancreatic Cancer CONKO-001 Trial Design R0 or R1 resected Pancreatic Ca N=368 R Gemcitabin...
Adjuvant treatment in resected Pancreatic Cancer CONKO-001- Results (ITT) Oettle JAMA 2007
Adjuvant treatment in resected Pancreatic Cancer CONKO-001- Results (ITT) Oettle JAMA 2007
ESPAC-3(v1) Trial Design Patients with ductal adenocarcinoma undergoing ‘curative’ resection Target N=990 RANDOMISE 5FU/ F...
ESPAC-3(v2) Trial Design Patients with ductal adenocarcinoma undergoing ‘curative’ resection Target N=1030* RANDOMISE 5FU/...
Br J Cancer 2009;  100 :246-50 No. at risk Gemcitabine Observation Cumulative survival % Months Disease free survival Obse...
Survival by Treatment Median S(t)= 23.0 months (95%CI:21.1, 25.0) Median S(t)= 23.6 months (95%CI:21.4, 26.4)  2 LR =0.74...
PFS by Treatment Median PFS(t)= 14.1months (95%CI:12.5, 15.3) Median PFS(t)= 14.3months (95%CI:13.5, 15.7)  2 LR =0.59, p...
Reported Toxicity Number of patients with at least one NCI CTC v2. grade 3/4 event  * Exploratory analysis: sig level p<0....
Adjuvant treatment in resected Pancreatic Cancer ESPAC-4 proposal Gemcitabine  + Capecitabine Gemcitabine Primary Outcome:...
Adjuvant Chemotherapy for Resected Pancreatic Cancer <ul><ul><li>We have information from two well designed positive rando...
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Medical Students 2011 - A. Cervantes - GASTROINTESTINAL CANCER - Pancreatic Cancer

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  • Medical Students 2011 - A. Cervantes - GASTROINTESTINAL CANCER - Pancreatic Cancer

    1. 1. PANCREATIC CANCER A CHALLENGE FOR MODERN MEDICINE IN THE 21 ST CENTURY
    2. 2. ETHIOLOGICAL FACTORS <ul><li>TOBACCO 2:1 </li></ul><ul><li>CRONIC PANCREATITIS </li></ul><ul><li>OBESITY </li></ul><ul><li>Not related </li></ul><ul><ul><li>Coffee </li></ul></ul><ul><ul><li>Alcohol </li></ul></ul><ul><ul><li>colelitiasis </li></ul></ul>
    3. 7. EARLY SYMPTOMS Y SIGNS OF PANCREATIC CANCER <ul><li>COMMON </li></ul><ul><ul><li>VISCERAL PAIN </li></ul></ul><ul><ul><li>WEIGHT LOSS </li></ul></ul><ul><ul><li>JAUNDICE (PANCREATIC HEAD) </li></ul></ul><ul><li>LESS FREQUENT </li></ul><ul><ul><li>GLUCOSE INTOLERANCE </li></ul></ul><ul><ul><li>PALPABLE GALLBLADDER </li></ul></ul><ul><ul><li>TROMBOFLEBITIS MIGRANS </li></ul></ul><ul><ul><li>GASTROINTESTINAL BLEEDING </li></ul></ul><ul><ul><li>SPLENOMEGALY </li></ul></ul>
    4. 8. CASE 3 A 65 YEAR OLD WOMAN WITH UNRESECTABLE PANCREATIC CANCER <ul><li>DIABETES MELLITUS DIAGNOSED ONE YEAR AGO </li></ul><ul><li>CONSULTED FOR WEIGHT LOSS OF 10KG IN 6 MONTHS, </li></ul><ul><li>ANOREXIA, </li></ul><ul><li>DEPRESSION AND </li></ul><ul><li>BACK PAIN INCREASING AT NIGHTS AND AT SUPINE POSITION THAT ONLY RELIEVES PARTIALLY WITH MOVEMENTS </li></ul>
    5. 9. CASE 3 A 65 YEAR OLD WOMAN WITH UNRESECTABLE PANCREATIC CANCER <ul><li>PHYSICAL EXAMINATION: </li></ul><ul><ul><li>NO HEPATOMEGALY </li></ul></ul><ul><ul><li>NO ASCITIS </li></ul></ul><ul><ul><li>NO JAUNDICE </li></ul></ul><ul><ul><li>RETROPERITONEAL PAIN ELICITED BY SOME SPECIFIC MANIOUVERS </li></ul></ul><ul><ul><li>NO EDEMA </li></ul></ul><ul><ul><li>NO PALLOR </li></ul></ul><ul><ul><li>PERFORMANCE STATUS 2 </li></ul></ul>
    6. 10. LABORATORY DATA IN PANCREATIC CANCER <ul><li>NONE OF THE IS SPECIFIC </li></ul><ul><li>OBSTRUCTIVE JAUNDICE </li></ul><ul><li>HYPERGLYCEMIA </li></ul><ul><li>CA 19.9 > 600 mU/ml </li></ul>
    7. 11. IMAGING FOR DIAGNOSIS AND STAGING PANCREATIC CARCINOMA <ul><li>ABDOMINAL ULTRASONOGRAPHY </li></ul><ul><li>HELYCAL CT-SCAN </li></ul><ul><li>RETROGRADE ENDOSCOPIC COLANGIOGRAPHY </li></ul><ul><li>ENDOSCOPIC ULTRASONOGRAPHY </li></ul><ul><li>MAGNETIC RESONANCE </li></ul><ul><li>ANGIOGRAPHY </li></ul>
    8. 12. CASE 3 A 65 YEAR OLD WOMAN WITH UNRESECTABLE PANCREATIC CANCER <ul><li>LABORATORY DATA: </li></ul><ul><ul><li>No anemia </li></ul></ul><ul><ul><li>No liver test alterations </li></ul></ul><ul><ul><li>Glucose: 210 mg/dl </li></ul></ul><ul><ul><li>CA19.9: 1200 IU/ml </li></ul></ul><ul><li>HELICAL CT SCAN OF THE ABDOMEN AND THORAX </li></ul><ul><ul><li>No liver or lung mets </li></ul></ul><ul><ul><li>Tumor located at the pancreatic body infiltrating retroperitoneal tissues and vascular structures (superior mesenteric artery) </li></ul></ul><ul><ul><li>Lymph nodes of significant size in retroperitoneal area </li></ul></ul><ul><li>BIOPSY </li></ul>
    9. 13. CLINICAL STAGING OF PANCREATIC CANCER <ul><ul><li>RESECTABLE </li></ul></ul><ul><ul><ul><li>T1-2 NX M0 </li></ul></ul></ul><ul><ul><ul><li>NO CELIAC AXIS INVOLVEMENT </li></ul></ul></ul><ul><ul><ul><li>NO SUPERIOR MESETERIC ARTERIAL INVOLVEMENT </li></ul></ul></ul><ul><ul><ul><li>NO EXTRAPANCREATIC INVOLVEMENT </li></ul></ul></ul><ul><ul><li>LOCALLY AVANCED UNRESECTABLE </li></ul></ul><ul><ul><ul><li>T3 NX-1 M0 </li></ul></ul></ul><ul><ul><ul><li>CELIAC AXIS OR MESENTERIC INVOLVEMENT </li></ul></ul></ul><ul><ul><li>METASTATIC </li></ul></ul><ul><ul><ul><li>METASTASES </li></ul></ul></ul><ul><ul><ul><ul><li>LIVER </li></ul></ul></ul></ul><ul><ul><ul><ul><li>PERITONEAL </li></ul></ul></ul></ul><ul><ul><ul><ul><li>LUNG </li></ul></ul></ul></ul><ul><ul><ul><ul><li>BONE </li></ul></ul></ul></ul>
    10. 25. <ul><li>CURE IS SOMEHOW EXCEPTIONAL </li></ul><ul><li>PALLIATIVE THERAPY </li></ul><ul><li>SYMPTOMS CONTROL </li></ul><ul><li>INDUCE OBJECTIVE RESPONSES </li></ul><ul><li>AVOID OR DELAY TUMOR PROGRESSION </li></ul><ul><li>IMPROVE OR MAINTAIN QUOALITY OF LIVE </li></ul><ul><li>PROLONG SURVIVAL </li></ul>AIMS OF TREATMENT FOR PATIENTS WITH ADVANCED OR METASTATIC SOLID TUMORS
    11. 26. CASE 3 A 65 YEAR OLD WOMAN WITH UNRESECTABLE PANCREATIC CANCER <ul><li>Therapeutic plan </li></ul><ul><ul><li>Control pain and anorexia-caquexia </li></ul></ul><ul><ul><li>Palliative chemotherapy with gemcitabine </li></ul></ul><ul><ul><li>Do consider experimental approaches </li></ul></ul>
    12. 27. CLINICAL BENEFIT USE OF ANALGESICS PAIN INTENSITY PAIN PERFORMANCE STATUS RESPONSE STABLE NO RESPONSE RESPONSE NO RESPONSE WEIGHT
    13. 28. GEMCITABINE 5-FU NR PATIENTS 63 63 TIME TO PROGRESSION p median 2.33 m .0002 0.92 m 6 months 22% 5% 12 months 9% 5% SURVIVAL median 5.65 m .0025 4.41 m 6 months 46% 31% 12 months 18% 2% CLASICAL PARAMETERS : 5FU BOLUS VS GEMCITABINE IN ADVANCED PANCREATIC CANCER
    14. 29. GEMCITABINE 5-FU Nr. Patients 63 63 Pain improvement 23.8% 4.8% Pain improvement With improved or stable PS 23.8% 4.8% Clinical benefit 23.8% 4.8% p=0.0022 CLINICAL BENEFIT: 5FU BOLUS VS GEMCITABINE IN ADVANCED PANCREATIC CANCER
    15. 30. GEMCITABINE 5-FU Nr. Patients 63 63 Pain improvement 23.8% 4.8% Pain improvement With improved or stable PS 23.8% 4.8% Clinical benefit 23.8% 4.8% p=0.0022 CLINICAL BENEFIT: 5FU BOLUS VS GEMCITABINE IN ADVANCED PANCREATIC CANCER BURRIS et al, J Clin Oncol 1997 .
    16. 31. STATHIS et al. Nat Rev Clin Oncol 2010
    17. 32. Heinemann V, et al BMC Cancer 2008
    18. 33. Heinemann V, et al BMC Cancer 2008
    19. 34. STATHIS et al. Nat Rev Clin Oncol 2010
    20. 37. Stratified by: - Center - PS (0/1 vs 2) - Stage of disease (locally advanced vs distant metastases) RANDOM I ZE Gemcitabine 1000 mg/m 2 IV + ERLOTINIB 100/150 mg po daily Gemcitabine 1000 mg/m 2 IV + Placebo 100/150 mg po daily GEMCITABINE +/- ERLOTINIB IN ADVANCED PANCREATIC CANCER : Design of PA.3 trial
    21. 38. GEMCITABINE +/- ERLOTINIB IN ADVANCED PANCREATIC CANCER : Overall Survival
    22. 40. A MULTIDISCIPLINARY APPROACH IS NEEDED TO TREAT PANCREATIC CANCER PANCREATIC CANCER IS RARELY CURED WITH SURGERY RESECTABILITY R0 RATE: 10-15% MEDIAN SURVIVAL: 11-13 MontHs 5-YR SURVIVAL: 15-20%
    23. 41. A MULTIDISCIPLINARY APPROACH FOR PANCREATIC CANCER TREATMENT PANCREATIC CANCER IS A A SYSTEMIC DISEASE ROLE OF ADJUVANT THERAPY CONTROL OF MICROMETASTATIC DISEASE REDUCE LOCAL AND SYSTEMIC RELAPSES DELAY RELPASES INCREASE SURVIVAL IMPROVE QUALITY OF LIFE
    24. 42. Signal transduction pathways via Ras and PI3K/Akt that cause cell proliferation and survival ■ EGFR ■ IGF‑1R ■ HGFR ■ VEGFR Developmental signaling pathways that can cause tumor progression and resistance to chemotherapy ■ Hedgehog ■ Notch ■ Wnt Tissue invasion and neovascularization ■ MMP DNA damage control and impaired apoptosis ■ p53 ■ p14 ARF/p16INK4A ■ SMAD4/TGF‑b PATHWAYS INVOLVED IN PANCREATIC CANCER
    25. 43. <ul><li>THE ABILITY TO UNDERGO SELF RENEWAL </li></ul><ul><li>THE DEVELOPMENTAL POTENTIAL TO RECAPITULATE ALL THE CELL TYPES FOUND IN A GIVEN TISSUE </li></ul><ul><li>SURFACE MARKERS: CD34+, CD44+, CD133+, ABCB5 </li></ul><ul><li>RESISTANCE TO CONVENTIONAL CT AND RT </li></ul>THE CANCER STEM CELLS : MAIN PROPERTIES Jordan CT. Cell Stem Cell 2009; 4:203.
    26. 44. THE CANCER STEM CELL HYPOTHESIS: THERAPEUTIC STRATEGIES TO TARGET TUMOUR-INITIATING CELLS Sergeant G., et al Nature Rev Clin Oncol 2009; 6:580.
    27. 45. THE CANCER STEM CELL HYPOTHESIS: THERAPEUTIC STRATEGIES TO TARGET TUMOUR-INITIATING CELLS Zhou BS. Nature Rev Drug Discov 2009; 8:806.
    28. 46. THE CANCER STEM CELL HYPOTHESIS: THERAPEUTIC STRATEGIES TO TARGET TUMOUR-INITIATING CELLS Zhou BS. Nature Rev Drug Discov 2009; 8:806.
    29. 47. A MULTIDISCIPLINARY APPROACH IS NEEDED TO TREAT PANCREATIC CANCER PANCREATIC CANCER IS RARELY CURED WITH SURGERY RESECTABILITY R0 RATE: 10-15% MEDIAN SURVIVAL: 11-13 MontHs 5-YR SURVIVAL: 15-20%
    30. 48. Adjuvant treatment in resected Pancreatic Cancer ESPAC-1 <ul><li>Pancreatic or ampullary adenocarcinoma, R0 or R1 </li></ul>Observation N=69 Chemoradiation N=73 Chemotherapy N=75 CRT and chemotherapy N=72 Treatment comparison Chemoradiotherapy vs. no CRT (144 vs. 145) Chemotherapy vs. no chemotherapy (142 vs. 147) R Neoptolemos et al, NEJM 2004
    31. 49. Survival rates 2-year 5-year No CRT: 41.4% 19.6% CRT: 28.5% 10.0% HR=1.28 (0.99, 1.66), p=0.053 ESPAC-1 NEJM 2004 ; 350:1200-10 ESPAC-1 NEJM 2004 : No benefit for Chemoradiation confirmed
    32. 50. Survival rates 2-year 5-year No CT: 30.0% 8.4% CT: 39.7% 21.1% HR=0.71 (0.55, 0.92), p=0.009 ESPAC-1 NEJM 2004; 350:1200-10 ESPAC-1 NEJM 2004 : Benefit for Chemotherapy confirmed
    33. 51. Adjuvant treatment in resected Pancreatic Cancer CONKO-001 Trial Design R0 or R1 resected Pancreatic Ca N=368 R Gemcitabine 1000mg/m 2 d1,8,15 q28d x6 Observation <ul><li>Stratified by: </li></ul><ul><li>R0 v R1 </li></ul><ul><li>T1/2 v T3/4 </li></ul><ul><li>N+ v N- </li></ul><ul><li>Primary Endpoint: </li></ul><ul><li>Disease free survival </li></ul><ul><li>Secondary Endpoints: </li></ul><ul><li>Toxicity, Quality of life, Overall survival </li></ul>Oettle JAMA 2007
    34. 52. Adjuvant treatment in resected Pancreatic Cancer CONKO-001- Results (ITT) Oettle JAMA 2007
    35. 53. Adjuvant treatment in resected Pancreatic Cancer CONKO-001- Results (ITT) Oettle JAMA 2007
    36. 54. ESPAC-3(v1) Trial Design Patients with ductal adenocarcinoma undergoing ‘curative’ resection Target N=990 RANDOMISE 5FU/ FA 5-FU 425mg/m 2 & FA 20mg/m 2 for 5 days every 28 days for 6 cycles Target N=330 GEMCITABINE 1000mg/m 2 once a week for 3 of 4 weeks for 6 cycles Target N=330 OBSERVATION Target N=330 330 per group to detect 10% difference in 2y survival rate (  = 5%, 1-  = 80%) Trial opened July 2000
    37. 55. ESPAC-3(v2) Trial Design Patients with ductal adenocarcinoma undergoing ‘curative’ resection Target N=1030* RANDOMISE 5FU/ FA Target N=515 Actual=551 GEMCITABINE Target N=515 Actual N=537 3-monthly follow-up to death 515 per group to detect 10% difference in 2y survival rate (  = 5%, 1-  = 90%) *Actual N=1088
    38. 56. Br J Cancer 2009; 100 :246-50 No. at risk Gemcitabine Observation Cumulative survival % Months Disease free survival Observation Gemcitabine Oettle et al JAMA, 2007 17;297:267-77 CONK01 Adjuvant Trial: Gemcitabine vs Observation ESPAC Adjuvant Trials: 5FU/FA vs Observation Survival rates 2-year 5-year Obs: 37% 14% 5FU/FA: 49% 24% Overall survival N = 458 N = 354 Log rank p < 0.001 Cumulative survival % HR= 0.68 (0.50, 0.92) p = 0.001 In the meantime!
    39. 57. Survival by Treatment Median S(t)= 23.0 months (95%CI:21.1, 25.0) Median S(t)= 23.6 months (95%CI:21.4, 26.4)  2 LR =0.74, p=0.39, HR GEM VS 5FU/FA =0.94 (95%CI: 0.81, 1.08) ESPAC 3 RESULTS REPORTED AT ASCO 2009
    40. 58. PFS by Treatment Median PFS(t)= 14.1months (95%CI:12.5, 15.3) Median PFS(t)= 14.3months (95%CI:13.5, 15.7)  2 LR =0.59, p=0.44, HR GEM VS 5FU/FA =0.95 (95%CI: 0.83, 1.09) ESPAC 3 RESULTS REPORTED AT ASCO 2009
    41. 59. Reported Toxicity Number of patients with at least one NCI CTC v2. grade 3/4 event * Exploratory analysis: sig level p<0.005 using Bonferroni adjustment p=0.013 p=0.94 p=0.0034* p=0.37 p=0.34 p<0.001* p=1.0 p=0.16 p<0.001* p=0.027 5FU/FA GEM CTC 3/4 (% of 551 pts) CTC 3/4 (% of 537 pts) WBC 32 (6%) 53 (10%) Neutrophils 121 (22%) 119 (22%) Platelets 0 8 (1.5%) Nausea 19 (3.5%) 13 (2.5%) Vomiting 17 (3%) 11 (2%) Stomatitis 54 (10%) 1 (0%) Alopecia 1 (0%) 1 (0%) Tiredness 45 (8%) 32 (6%) Diarrhoea 72 (13%) 12 (2%) Other 67 (12%) 43 (8%)
    42. 60. Adjuvant treatment in resected Pancreatic Cancer ESPAC-4 proposal Gemcitabine + Capecitabine Gemcitabine Primary Outcome: Overall Survival Resected pancreatic cancer Secondary Outcomes: DFS, Toxicity, QOL
    43. 61. Adjuvant Chemotherapy for Resected Pancreatic Cancer <ul><ul><li>We have information from two well designed positive randomized studies showing survival benefit </li></ul></ul><ul><ul><li>Better staging system and optimal surgical centers with high volume and good experience should be a priority </li></ul></ul><ul><ul><li>FU/LV or gemcitabine are useful agents </li></ul></ul><ul><ul><li>Gemcitabine is preferred for its more favourable profile </li></ul></ul><ul><ul><li>It is a well established standard of care with evidence level I recommendation grade A </li></ul></ul>

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