1. Metastatic Unresectable, not metastatic Resectable Treatment Pathways for Carcinoma of the Pancreas

2. Metastatic cancer

3. Robert L Fine, William Sherman, John Chabot, Stephen Schreibman, Michael Williams, Michael Cusnir, David Van Echo, Columbia Universirty, College of Physicians and Surgeons, New York, NY; University of Virginia, Charlottesville, VA; University of Maryland, Baltimore, MD. GTX Chemotherapy for Pancreatic Cancer

4. PC cells frequently have ras and p53 mutations that block certain apoptosis pathways. Chemotherapy drugs should be screened in vitro against cell lines with ras and p53 mutations. Hypothesis

5. There is synergism between 5-FU and gemcitabine and between gemcitabine and taxotere. Synergism between gemcitabine and taxotere was observed at nanomolar concentrations of taxotere. In vitro findings:

6. In Vitro Schedule-dependent Interaction between Docetaxel and Gemcitabine in Human Gastric Cancer Cell Lines Luca Ricotti, Anna Tesei, Franca De Paola, Paola Ulivi, Giovanni Luca Frassineti, Carlo Milandri, Dino Amadori and Wainer Zoli Clinical Cancer Research Vol. 9, 900-905, February 2003 Doc + Gem Gem  Dox Dox  Gem

7. Xeloda 1500 – 2000 mg/m 2 /day in 2 daily doses, Day 1 – 14 Gemcitabine 750 - 1000 mg/m 2 i.v. over 2 hours, Day 4, 11 Taxotere 30 mg/m 2 i.v. Day 4, 11 Fine, Sherman, et al. ASCO 2002, p144a, abstract #575 GTX

8. 24 patients with metastatic tumor: PR50% SD25% NR25% Fine, Sherman, et al. ASCO 2002, p144a, abstract #575 GTX

9. Other protocols for metastatic carcinoma of the pancreas Cis-platinum + irinotecan Cis-platinum + gemcitabine

10. Treatment Pathways for Carcinoma of the Pancreas Unresectable, not metastatic

11. 8 patients with locally advanced tumor treated with GTX -> Radiation + weekly Gemcitabine -> Surgery: 5 had Whipple with negative margins and normal post-op CA 19-9 Downstaging patients with locally advanced, non-metastatic tumor Fine, Sherman, et al. ASCO 2002, p144a, abstract #575

12. Treatment Pathways for Carcinoma of the Pancreas S/p resection, no known residual or metastatic tumor

13. Nukui, Picozzi, Traverso. Am J Surg 2000; 179: 367-71 Interferon-based adjuvant chemoradiation after pancreaticoduodenectomy for pancreatic adenocarcinoma External beam radiation 4,500 cGy to 5,400 cGy, 25 fractions in 5 weeks Cis-platinum 30 mg/m 2 once a week 5-FU 200 mg/m 2 /day continuous i.v. infusion  -interferon 3 x 10 6 u sq every other day Followed by continuous i.v. 5-FU weeks 9  14 and 17  22

14. Nukui, Picozzi, Traverso. Am J Surg 2000; 179: 367-71 Interferon-based adjuvant chemoradiation after pancreaticoduodenectomy for pancreatic adenocarcinoma Between 1993 and 1998 33 patients at VMMC, Seattle WA had adjuvant therapy with a) “GITSG” bolus 5-FU and radiation orb) “IFN based” chemoradiation Not a randomized trial Comparable stage and prognostic factors in both groups

15. Nukui, Picozzi, Traverso. Am J Surg 2000; 179: 367-71 Interferon-based adjuvant chemoradiation after pancreaticoduodenectomy for pancreatic adenocarcinoma

16. Nukui, Picozzi, Traverso. Am J Surg 2000; 179: 367-71 Interferon-based adjuvant chemoradiation after pancreaticoduodenectomy for pancreatic adenocarcinoma 26 month median follow-up: 2-year survival GITSG style54% IFN-based84%

17. Interferon-based adjuvant chemoradiation after pancreaticoduodenectomy for pancreatic adenocarcinoma Audit and update by committee from ACOS: 53 patients treated at VMMC analyzed with adjuvant “Ifn-based” chemoradiation and 5-FU after Whipple 49% 5-year survival

18. Interferon-based adjuvant chemoradiation after pancreaticoduodenectomy for pancreatic adenocarcinoma 70% required treatment delay 43% required hospitalization 90% received full dose of radiation 85% received full dose of chemotherapy

19. ACOSOG Z5031 - Phase II Study Eligibility: R0 or R1 resection T 1 - T3, N0 - N1, M0 Adenocarcinoma of head of pancreas Changes in treatment compared to VMMC study: 175 mg/m 2 /day 5-FU instead of 200 mg/m 2 /day 5040 cGy in 28 fractions - 180 cGy fractions instead of 200 cGy fractions