Pancreatic cancer

1. Pancreatic cancerchemotherapyJarosław Reguła M.D.Department of Gastroenterology, Institute of Oncology, Warsaw, Poland

2. Pancreatic cancer • 10-th common cancer • 4-th cause of cancer death • Overall 5-year survival – ca. 4%

3. general status (Karnofsky) • supportive care TNM staging • palliation • surgery alone • surgery + adjuvant therapy • chemotherapy Diagnosis established

4. Combined therapy • Neo-adjuvant therapy = before surgery • Adjuvant = after surgery • Sequential or concomittant (eg. CTH & RTH)

5. T staging

6. T3 –locally advanced Extends beyond pancreas but no involvement of celiac axis or superior mesenteric artery Potentially resectable in expert centres

7. T4 Involvement of celiac axis or superior mesenteric artery

8. No or N1 (number of lymph nodes involved does not need to be defined

9. Stage groups Stage 0 Tis N0M0 Stage I A T1 N0M0 potentially resectable Stage I B T2 N0M0 Stage II A T3 N0M0 usually potentially resectable Stage II B T1-3 N1M0 Stage III T4 N0-1 M0 locally advanced, not resectable due to CA or SMA involvement Stage IV T1-4 N0-1 M1 metastatic

10. Resection • R classification (residual tumour) • R0: tumour resected macroscopically and microscopically completely • R1: tumour resected completely macroscopically but incompletely microscopically • R2: resection incomplete macroscopically

12. Stage I/II patients

18. Neoptolemos NEJM, 2004

23. ESPAC-3 • The largest ever trial on adjuvant therapy in pancreatic cancer • 1100 patients in 17 European counties • Arm A: 5-FU/folinic acid • Arm B: gemcitabine day 1,8,15 every 28 days • Results are awaited

24. Clear benefit from adjuvant chemotherapy after resection

25. Standard adjuvant therapies • USA – adjuvant chemoradiotherapy • Europe – adjuvant chemotherapy Debate continues

26. Advanced disease - usual survival • Localized disease – ca. 1 year • Metastatic disease – ca. 6 months • Endpoints: • Overall survival • Quality of life • Clinical benefit response (CBR): (pain, KPS, weight)

27. Main agents for chemotherapy • 5-FU – 600 mg/m2 weekly • Gemcitabine – 1000 mg/m2 weekly for 7 weeks (1 week off) + wekly 3 weeks with 1 week off

28. 5-FU vs gemcitabine 5-FU Gemcitabine Survival (median) 4,4 mo 5,6 mo 12 month survival 2% 18% CBR 4,8% 23,8%

29. FDR Gemcitabine • Increasing time of infusion holding the dose rate constant • Conflicting results • Most administer the drug in a standard way

30. Capecitabine (Xeloda) • Orally • Pro-drug of 5-FU • Combination Gemcitabine+capecitabine vs gemcitabine for patients Karnofsky status 90-100 points overall survival benefit 10,4 monts vs 7,4 months Herrmann 2007

31. Targeted therapies • EGFR inhibitors: • Erlotinib • cetuximab • VEGF inhibitors • Bevacuzimab • Others

34. Real life (Institute of Oncology, Warsaw) • Resectable tumour: - adjuvant chemotherapy (gemcitabine) – standard dosing - adjuvant radiochemotherapy as research programme • Palliative therapy • Gemcitabine (standard) until progression or toxicity • Gemcitabine + Xeloda (non standard approach • Second line • FAM (5-FU+ adriamycin + mitomycin) • Clinical trials with anti-EGFR

35. Summary • Proper staging is crucial for planning therapy • Selection of patients for a given therapy is difficult • Resectable patients should have adjuvant therapy (gemcitabine) providing good general status • Palliative therapy (gemcitabine monotherapy) • Numerous trials exist

36. Question 1Tumour extending beyond pancreas, not inflitrating CA or SMA is: • 1) T1 • 2) T2 • 3) T3 • 4) T4

37. Question 2T4N1M0 is unresectable due to: • 1) metastatic disease • 2) involvement of SMA or CA • 3) lymph node involvement • 4) Karnofsky status 30%

38. Question 3:Capecitabine is • 1) oral gemcitabine • 2) oral 5FU • 3) oral cetuximab • 4) oral oxaliplatine