1. Carcinoma do Pâncreas Terapêutica Adjuvante e Neoadjuvante: Fundamentos da Radioquimioterapia Rui Paulo Rodrigues Departamento de Radioterapia – Hospital CUF Descobertas – Lisboa http://rt.no.sapo.pt

6. Carcinoma do Pâncreas Fundamentos da Radioquimioterapia Radioquimioterapia na doença localmente avançada Ensaios fase III no carcinoma localmente avançado do pâncreas RTE=radioterapia externa; 5-FU=5-flururacilo; * valores calculados a partir dos originais em semanas 7.7* (p>0.8) 78 RTE 40 Gy + doxorrubicina 8.6* 79 RTE 60 Gy + 5-FU (bolus) GITSG 1985 5.3* (p<0.02) 25 RTE 60 Gy 11.5* 86 RTE 60 Gy + 5-FU (bolus) + 5-FU (manutenção) 8.5* 83 RTE 40 Gy + 5-FU (bolus) + 5-FU (manutenção) GITSG 1979 10.4 32 RTE 35-40 Gy + 5-FU (bolus) 6.3 32 RTE 35-40 Gy Clinica Mayo 1969 S.mediana (m) n Tratamento Ensaio

7. Carcinoma do Pâncreas Fundamentos da Radioquimioterapia Radioquimioterapia na doença localmente avançada Ensaios fase II no carcinoma localmente avançado do pâncreas – novas drogas RTE=radioterapia externa; 5-FU=5-flururacilo; IC=infusão contínua; DFUR=Doxifluridine 44 32 38 38 35 25 n -- 8 Paclitaxel / RTE 50.4 Gy Univ.Brown 2001 -- 9 5-DFUR, LV / RTE 50 Gy Milão 1999 18 14 5-FU , LV, CDDP / RTE 55 Gy Univ.Viena 2000 -- 15.5 5-FU. LV, MMC, dipiridamole UCLA 1998 26 15 5-FU, strept, CDDP (x2) / RTE 54 Gy / Manutenção 5-FU + LV (inop’s) Mout Sinai 1997 18 11.9 5-FU (IC) / RTE 59.4 Gy Whittington 1995 S.2 anos (%) S.mediana (m) Tratamento Ensaio

15. Carcinoma do Pâncreas Fundamentos da Radioquimioterapia Radioquimioterapia pré-operatória Ensaios de radioquimioterapia neoadjuvante - - 4 3 8 Cirurgia - - 6** 3 - Resp. 20 & 24 # 4 1 5 Ressecção Smed: 23.6 & vs. 14 meses - 68 Mount Sinai 2000 Smed: 15.7 # vs. 9.7 meses 0 53 Fox Chase 1998 Smed: 28** vs. 15.5* meses 4 38* UCLA 1998 Fal. em 18 meses por rec. 1 87 MSKCC 2002 Progressão em 17 meses 1 25 Duke Univ. 1999 Obs. R0 n Ensaio

18. Carcinoma do Pâncreas Fundamentos da Radioquimioterapia Radioterapia intraoperatória Ensaios fase II com RTIO no carcinoma avançado do pâncreas RTIOE=radioterapia intraoperatória com electrões; RTE=radioterapia externa; 5-FU=5-flururacilo 12 13 -- 68 RTIOE + RTE 35-40 Gy / 5-FU (?) Gunderson 1997 31 49 56 27 51 n RTIOE + RTE 50-60 Gy / QT RTIOE + RTE 55 Gy / 5-FU+LV RTIOE + RTE 35-40 Gy / 5-FU RTE 50-54 Gy / 5-FU + RTIOE RTIOE + RTE 35-40 Gy / 5-FU Tratamento -- 31 -- 22 -- Rec.loc (%) 14 8.2 Nishimura 1997 22 16 Mohiuddin 1995 6 10.5 27 14.9 Mayo 1993 9 (18 m) 9 RTOG 1991 S.2 anos (%) S.mediana (m) Ensaio

23. Carcinoma do Pâncreas Fundamentos da Radioquimioterapia National Cancer Institute (NCI) Ensaios abertos em 11/11/2003 - http://clinicaltrials.gov/ct/action/GetStudy Eastern Cooperative Oncology Group Gemcitabine With or Without Radiation Therapy in Treating Patients with Pancreatic Cancer Randomized phase III trial to study the effectiveness of gemcitabine with or without radiation therapy in treating patients who have locally advanced, unresectable pancreatic cancer. Cancer and Leukemia Group B Combination Chemotherapy and Radiation Therapy in Treating Patients With Pancreatic Cancer National Phase II trial to study the effectiveness of combination chemotherapy and radiation therapy in treating patients who have locally advanced pancreatic cancer.

24. Carcinoma do Pâncreas Fundamentos da Radioquimioterapia National Cancer Institute (NCI) Ensaios abertos em 11/11/2003 - http://clinicaltrials.gov/ct/action/GetStudy EORTC Gastrointestinal Tract Cancer Cooperative Group; EORTC Radiotherapy Cooperative Group; Federation Francophone de Cancerologie Digestive Gemcitabine and Radiation Therapy Compared With Observation in Treating Patients Who Have Undergone Surgery for Pancreatic Cancer Randomized phase II/III trial to compare the effectiveness of gemcitabine combined with radiation therapy with that of observation alone in treating patients who have undergone surgery for pancreatic cancer. Eastern Cooperative Oncology Group Chemotherapy and Radiation Therapy in Treating Patients With Locally Advanced Pancreatic Cancer Randomized phase II trial to compare the effectiveness of two different regimens combining chemotherapy with radiation therapy in treating patients who are undergoing surgery for locally advanced pancreatic cancer.