1. TREATMENT OF POTENTIALLY RESECTABLE PANCREATIC CANCER: A CLINICAL ONCOLOGIST‘S POINT OF VIEW

2. Conventional treatment strategy in patients with potentially resectable disease: Surgery ± adjuvant (radio)chemotherapy

3. B. Gudjonsson Critical look at resection for pancreatic cancer (Lancet 348:1676, Dec. 1996) “ In pancreatic cancer 5-year survivors are rare, cure is exceptional, the operative mortality is significant, and the costs of the resection are excessive ......“

6. JL. Abbruzzese (ASCO 2000 Educational Booklet, pp.19-23) “ Thus, at this point in time the weight of evidence does not strongly support the use of postoperative therapy in patients with resected pancreatic cancer .......“

8. 142 Patients with potentially resectable pancreatic or periampullary carcinomas Histologically ascertained CT visible mass in the pancreatic head Negative histology or CT non-visible tumor 5-FU 300 mg/m2/day CI x5/week + radiotherapy 50.4 Gy for 5.5 weeks (standard fractionation 1.8 Gy/day x5/week) or 5-FU 300 mg/m2/day CI x5/week + hyperfractionated radiotherapy 30 Gy for 2 weeks (3 Gy/day x5/week) Duodenopancreatectomy R0 resected pancreatic cancer: Radiochemotherapy (using standard fractions) (Spitz et al. 1997)

9. Potential resectable carcinomas of the pancreatic head (n=142) Preoperative radiochemotherapy 91 Laparotomy 67 Curative resection 52 non resectable 9 no adjuvant therapy 6 no pancreatic cancer 17 Progression 24 non resectable 15 Laparotomy 51 Curative resection 42 Pancreatic cancer 25 Postoperative Radiochemotherapy 19

10. Results of Treatment (Spitz et al., 1997) Preoperative Radiochemotherapy Postoperative Radiochemotherapy Recurrence rate: 27/41 (66%) 11/19 (58%) Median survival: 19.2 months 22 months

11. Advantages of the conventional therapeutic concept (surgery » radiochemotherapy) 1.) In 9/51 patients (18%) disseminated disease was found intraoperatively 2.) In 17/51 patients (33%) periampullary adeno- carcinomas were diagnosed 3.) Adjuvant radiochemotherapy was tolerated as well as preoperative treatment

12. Positive aspects of preoperative Radiochemotherapy: 1.) Multimodal therapeutic concept could be realized in all patients 2.) Unnecessary surgery could be avoided in 26% of the patients 3.) No delay of surgery, no increase in perioperative morbidity & mortality 4.) Significantly shorter treatment duration in the hyperfractionated arm (62 vs. 99 days) 5.) Counteracts frequent non R0-resection of retroperitoneal margins 6.) No locoregional tumor recurrence (0/41 versus 2/19) 7.) Similar median survival despite more advanced tumor stages (19.2 versus 22 mos)

15. In order to improve therapeutic results, more effective systemic chemotherapy regimens are required !

23. Evolution of multimodality neoadjuvant therapy in patients with localized pancreatic cancer Standard fractionation combined CRT  surgery Short-course hyper-fractionation CRT  surgery (reduces GI-toxicity and treatment duration) Improved systemic CT  CRT  surgery (more effective regimens with full drug doses can be given, improved preselection of patients with resectable disease)