pancreatic cancer yoo-joung ko. recent media exposure october 23, 1960 – july 25, 2008 died 2...
TRANSCRIPT
![Page 1: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/1.jpg)
Pancreatic CancerYoo-Joung Ko
![Page 2: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/2.jpg)
Recent Media Exposure
October 23, 1960 – July 25, 2008Died 2 years after undergoing a Whipple procedure in 2006
![Page 3: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/3.jpg)
Patrick Swayze
Diagnosed with stage IV pancreatic cancer Jan 2008Died Sept 14, 2009
![Page 4: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/4.jpg)
Overview
Epidemiology
Risk Factors
Pathology
Presentation
Surgical treatment
Adjuvant therapy
Treatment of metastatic disease
![Page 5: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/5.jpg)
2007 Estimated US Cancer Cases*
*Excludes basal and squamous cell skin cancers and in situ carcinomas except urinary bladder.Source: American Cancer Society, 2007.
Men766,860
Women678,060
26% Breast
15% Lung & bronchus
11% Colon & rectum
6% Uterine corpus
4% Non-Hodgkin lymphoma
4% Melanoma of skin
4% Thyroid
3% Ovary
3% Kidney
3% Leukemia
21% All Other Sites
Prostate 29%
Lung & bronchus 15%
Colon & rectum 10%
Urinary bladder 7%
Non-Hodgkin4% lymphoma
Melanoma of skin 4%
Kidney 4%
Leukemia 3%
Oral cavity 3%
Pancreas 2%
All Other Sites 19%
10th most common cancer
![Page 6: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/6.jpg)
2007 Estimated US Cancer Deaths*
ONS=Other nervous system.Source: American Cancer Society, 2007.
Men289,550
Women270,100
26% Lung & bronchus
15% Breast
10% Colon & rectum
6% Pancreas
6% Ovary
4% Leukemia
3% Non-Hodgkin lymphoma
3% Uterine corpus
2% Brain/ONS
2% Liver & intrahepaticbile duct
23% All other sites
Lung & bronchus 31%
Prostate 9%
Colon & rectum 9%
Pancreas 6%
Leukemia 4%
Liver & intrahepatic 4%bile duct
Esophagus 4%
Urinary bladder 3%
Non-Hodgkin 3% lymphoma
Kidney 3%
All other sites 24%
4th leading cause of cancer death
![Page 7: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/7.jpg)
JP Hoffman ASCO 2006
![Page 8: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/8.jpg)
Poor Survival
AJCC Stage Median Survival
Resectable (I-II) 14-25months
Locally Advanced (II) 8-15 months
Metastatic (IV) 3-7 months
![Page 9: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/9.jpg)
Risk Factors
•Smoking•Age, gender•Obesity•Diet – high fat, low fibre•Chronic pancreatitis•Family history – BRCA2•Β-napthylamine
![Page 10: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/10.jpg)
Clinical Presentation
Painless obstructive jaundice (pancreatic head tumors -2/3)
Abdominal pain
Anorexia, weight loss
Trousseau’s sign
Depression
diabetes
![Page 11: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/11.jpg)
Sites of Metastasis
Liver
Peritoneum
Lung
Adrenal
Bone
Rarely CNS
![Page 12: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/12.jpg)
Pancreatic Epithelial Malignancies
Malignant Ductal adenocarcinoma (majority) Mucinous cystadenocarcinoma Acinar cell carcinoma Small cell carcinoma
Uncertain malignant potential Mucinous cystadenoma Solid and cystic papillary neoplams
![Page 13: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/13.jpg)
Ductal Adenocarcinoma
•Nuclear atypia•Significant fibrosis
![Page 14: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/14.jpg)
Treatment Approach
![Page 15: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/15.jpg)
Patient Workup
Birphasic CT
ERCP + stent + /- biopsy
PET scan for possible resection
![Page 16: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/16.jpg)
Surgical Resectability
No evidence of extra-pancreatic disease Liver Retroperitoneum Peritoneal disease
No evidence of SMA, hepatic or celiac encasement (>180 degrees)
Fewer than 20% are surgical candidates
![Page 17: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/17.jpg)
Whipple Procedure
Goal is R0 resection R2 or R1 resection have
outcomes similar to unresectable nonmetastatic disease
Operative mortality is associated with high volume centres
![Page 18: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/18.jpg)
Effect of Hospital Volume
![Page 19: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/19.jpg)
How good is surgery?
Does a whipple increase survival by minutes?
![Page 20: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/20.jpg)
Post Surgical Therapy
No standard of care for adjuvant therapy
European standard Chemotherapy alone
US standard chemoradiotherapy
![Page 21: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/21.jpg)
GITSG- Cancer 1987
First randomized study
N=43!!!
Observation versus RT (splite course, 40 Gy + FU bolus then adjuvant 5FU)
2 year survival 46% versus 18%
![Page 22: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/22.jpg)
European Standard: ESPAC-1
![Page 23: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/23.jpg)
Survival rates 2-year 5-yearNo CRT: 41.4% 19.6%CRT: 28.5% 10.0%HR=1.28 (0.99, 1.66), p=0.053
ESPAC-1ESPAC-1
NEJMNEJM 2004 2004; ; 350:1200-10 350:1200-10
ESPAC-1 NEJM 2004: No benefit for Chemoradiation confirmed
![Page 24: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/24.jpg)
Survival rates 2-year 5-yearNo CT: 30.0% 8.4%CT: 39.7% 21.1%HR=0.71 (0.55, 0.92), p=0.009
ESPAC-1ESPAC-1
NEJM 2004; NEJM 2004; 350:1200-10 350:1200-10
ESPAC-1 NEJM 2004: Benefit for Chemotherapy confirmed
![Page 25: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/25.jpg)
ESPAC 1 Trial
Lack QA for RT plans
RT field size and techniques not specified
Split course RT used, low dose (20 Gy/10 f x 2)
![Page 26: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/26.jpg)
US approach: Study Design
Note that absence of no XRT arm
![Page 27: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/27.jpg)
![Page 28: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/28.jpg)
![Page 29: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/29.jpg)
Gem 5FUMed survival 20.5 m 16.9 m3 yr survival 31% 22%
WF Regine et al JAMA 299:1019-1029, 2008
RTOG 9704 Trial
![Page 30: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/30.jpg)
![Page 31: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/31.jpg)
![Page 32: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/32.jpg)
RTOG 9704 Trial
WF Regine et al JAMA 299:1019-1029, 2008
![Page 33: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/33.jpg)
CONKO-1
![Page 34: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/34.jpg)
CONKO 1 Trial
surgery vs postop gem alone
Total of 368 pts with R0/R1 resection
Gem 1000 mg/m2 weekly 3 of 4 wks
Primary endpoint was DFS, not OS
Only included pts with Ca 19-9 <2.5 x normal
![Page 35: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/35.jpg)
Oettle et al JAMA 297:267-277, 2007
CONKO-001 Trial
Med DFS 13.4 m Gem 6.9 m Obs
OS 3/5 yr 34/22.5% Gem 20.5/11.5% Obs
![Page 36: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/36.jpg)
H Oettle et al JAMA 297:267-277, 2007
CONKO-001 Trial: R1 vs R0
Med surv 13.1 m Gem 7.3 m Obs
Med surv 15.8 m Gem 5.5 m Obs
![Page 37: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/37.jpg)
Br J Cancer 2009; Br J Cancer 2009; 100 :246-50
ESPAC Adjuvant Trials: 5FU/FA vs ESPAC Adjuvant Trials: 5FU/FA vs ObservationObservation
Survival rates 2-year 5-yearObs: 37% 14%5FU/FA: 49% 24%
Overall survival
N = 458
Cu
mu
lati
ve s
urv
ival
%
HR= 0.68 (0.50, 0.92) p = 0.001
![Page 38: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/38.jpg)
ESPAC-3(v1) Trial DesignPatients with ductal adenocarcinoma
undergoing ‘curative’ resectionTarget N=990
RANDOMISE
5FU/ FA5-FU 425mg/m2 &FA 20mg/m2 for 5
days every 28 days for 6 cycles
Target N=330
GEMCITABINE1000mg/m2 once a
week for 3 of 4 weeks for 6 cycles
Target N=330
OBSERVATIONTarget N=330
330 per group to detect 10% difference in 2y survival rate ( = 5%, 1-= 80%)
Trial opened July 2000
![Page 39: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/39.jpg)
Eligibility Complete macroscopic resection for pancreatic
ductal adenocarcinoma (WHO Classification)
R0 or R1 resection
No: ascites, liver or peritoneal metastasis, or any other distant abdominal or extra-abdominal organ spread
No previous or concurrent malignancy diagnoses
WHO performance status < 2
Life-expectancy of more than 3 months
Fully informed written consent
![Page 40: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/40.jpg)
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)
2LR=0.74, p=0.39, HRGEM VS 5FU/FA=0.94 (95%CI: 0.81, 1.08)
![Page 41: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/41.jpg)
PFS by TreatmentMedian PFS(t)= 14.1months (95%CI:12.5, 15.3)Median PFS(t)= 14.3months (95%CI:13.5, 15.7)
2LR=0.59, p=0.44, HRGEM VS 5FU/FA=0.95 (95%CI: 0.83, 1.09)
![Page 42: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/42.jpg)
Reported Toxicity
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%)
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
![Page 43: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/43.jpg)
Conclusions
No difference in survival between adjuvant gemcitabine and 5-FU/FA in patients with resected pancreatic cancer
The safety profile of gemcitabine was better than that of 5-FU/FA
Data reinforce the perfect design of the ESPAC-4 trial comparing gemcitabine with the combination of gemcitabine with capecitabine
![Page 44: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/44.jpg)
Treatment Approach
![Page 45: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/45.jpg)
Palliation of Pancreatic Cancer
Pain management eg nerve block
Obstructive jaundice Percutaneous drain versus internal stent Metal versus plastic
Thromboembolism up to 20%
Depression
Fatigue, anorexia, weight loss
![Page 46: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/46.jpg)
Chemotherapy versus BSC
Meta-analysis 3458 patients in 29 trials 9 trials with 5-FU combination vs BSC Median survival 6.4 vs 3.9 months
![Page 47: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/47.jpg)
Phase III study of Gemcitabine vs 5-FU
Multi-centre, single-blind, randomized study
Clinical benefit primary endpoint
Burris et al JCO 1997
![Page 48: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/48.jpg)
Gemcitabine vs 5-FU survival
![Page 49: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/49.jpg)
Gemcitabine + Bevacizumab in
Pancreatic cancer
![Page 50: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/50.jpg)
Gemcitabine + Bevacizumab
Phase II trial (n=52)
Metastatic advanced pancreatic cancer
Response: PR – 21%, SD – 46%
Median PFS: 5.4 months
Median OS: 8.8 months
VEGF levels did not correlate with outcome
GI perforation 8%, one pt : Gr 5 GI bleed
Kindler et al. JCO 23: 8033-40, 2005.
![Page 51: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/51.jpg)
Next Step: Phase III
CALGB 80303 – Gemcitabine With Versus Without Bevacizumab in Advanced
Pancreatic Cancer
Anticipated accrual : 602 patients
Press release June, 2006: Trial closed early at interim analysis due to poor efficacy in experimental arm
![Page 52: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/52.jpg)
![Page 53: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/53.jpg)
![Page 54: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/54.jpg)
![Page 55: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/55.jpg)
![Page 56: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/56.jpg)
What happened?
![Page 57: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/57.jpg)
![Page 58: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/58.jpg)
EGFR Agents in Pancreatic Cancer
The Greatest Thing Since …?EGFR antagonists in NSCLC?
![Page 59: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/59.jpg)
![Page 60: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/60.jpg)
NCIC PA.3
Gemcitabine plus erlotinib: 1st combination therapy to demonstrate a survival advantage over gemcitabine alone
![Page 61: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/61.jpg)
![Page 62: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/62.jpg)
Gemcitabine + Cetuximab
Phase II trial (n=41)
EGFR-positive advanced pancreatic cancer
Response: PR – 12.2%, SD – 63.4%
Median TTP: 3.8 months
Median OS: 7.1 months, 1 yr OS = 31.7%
Acneiform rash common (~90%) Severity of rash correlated with survival
Xiong et al. JCO 22: 2610-16, 2004.
![Page 63: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/63.jpg)
![Page 64: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/64.jpg)
![Page 65: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/65.jpg)
![Page 66: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/66.jpg)
![Page 67: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/67.jpg)
![Page 68: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/68.jpg)
![Page 69: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/69.jpg)
![Page 70: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/70.jpg)
![Page 71: Pancreatic Cancer Yoo-Joung Ko. Recent Media Exposure October 23, 1960 – July 25, 2008 Died 2 years after undergoing a Whipple procedure in 2006](https://reader036.vdocuments.site/reader036/viewer/2022062421/56649da65503460f94a9181f/html5/thumbnails/71.jpg)
What lessons have we learned?
•Locally advanced and metastatic disease should be separated•VEGF inhibition not encouraging•EGFR inhibition not encouraging•Role of combination biologic therapy?•Other targets?•Combination with capecitabine?