La presentazione è in caricamento. Aspetta per favore

La presentazione è in caricamento. Aspetta per favore

Il trattamento delle metastasi epatiche neoplasie del colon retto Filippo de Braud MD Clinical Pharmacology and New Drugs Development Unit European Institute.

Presentazioni simili


Presentazione sul tema: "Il trattamento delle metastasi epatiche neoplasie del colon retto Filippo de Braud MD Clinical Pharmacology and New Drugs Development Unit European Institute."— Transcript della presentazione:

1 Il trattamento delle metastasi epatiche neoplasie del colon retto Filippo de Braud MD Clinical Pharmacology and New Drugs Development Unit European Institute of Oncology Milano Italy

2 Trattamento neoadiuvante delle metastasi epatiche resecabili Trattamento neoadiuvante delle metastasi epatiche non resecabili Trattamento adiuvante post-resettivo Trattamento delle metastasi epatiche sincrone da cancro del retto Trattamento delle metastasi epatiche con minima malattia extraepatica

3 ADVANCED COLORECTAL-CANCER: DISEASE LIMITED TO THE LIVER SURGICAL RESECTION STUDIES > 2500 PTS Mortality 1- 5 % 1 yr surv80 % 5 yrs surv % Sem. Oncol. 26, 5: , 1999

4 ADVANCED COLORECTAL-CANCER: DISEASE LIMITED TO THE LIVER SURGICAL RESECTION WHEN IT IS POSSIBLE BUT….. WHEN IS IT POSSIBLE ?

5 ADVANCED COLORECTAL-CANCER: LIVER RESECTION Disease Related Factors AGE IS NOT (Fong et al, Ann Surg 222: 426, 1995) MARGINS : It does not make sense Size of Largest Met > 5 cm Disease Free Interval < 12 mos Number of Mets > 3 Primary Node Positive CEA > 200 ng/mg (JCO, 15: , 1997)

6 ADVANCED COLORECTAL-CANCER: LIVER RESECTION Disease Related Factors Score Surv (%) Median 1yr 5yr months JCO, 15: , 1997

7 Fong Y. et al, Ann Surg 1999, 230:

8 SURGICAL RESECTION Results are very reproducible !

9 ADVANCED COLORECTAL-CANCER RESECTION OF LIVER METS Study# pts5-yrs OS Median Survival months Hughes %- Scheele %40 Nordinger %- Jamison %33 Fong %42

10 Metastasi epatiche nel carcinoma del colon retto 2.Malattia solo epatica non operabile Chemioterapia intraarteriosa? Chemioterapia sistemica? Chemioterapia sistemica + intraarteriosa? Terapia neo-adiuvante?

11 Survival after primary and secondary resection of liver metastases Adam R, Ann Oncol 2003;14: ii13-ii16 Resectable (n=425) Initially unresectable (n=95) Surviving (%) 54% 50% 34% 27% 29% 19% Survival time (years)

12 Neoadjuvant chemotherapy Paul Brousse hospital study Adam R et al., Ann Surg Oncol 8:347-53, 2001 N= 872 N=171 Primary resectable 20% of all patients Initially unresectable N=701 Never resectable N=95 Secondary resectable 11% of all patients 14% of CT-treated Resection: 266 patients (31%) Oxaliplatin/5FU/LV

13 Oxaliplatino Metastasi epatiche da Carcinoma Colon Bismuth pazienti con metastasi epatiche inoperabili –N. pz. operati53 (16%) –Resezione curativa46 (75%) –OSa 3 anni54% a 5 anni40% Giacchetti, Ann Oncol pz. con metastasi epatiche inoperabili trattati con Oxa + 5FU (83% con cronoterapia): – 59% RP – OS casistica 24 mesi (28% vivi a 5 aa) – 51% operati (38% resezione radicale) – OS operati 48 mesi (50% vivi a 5 aa)

14 Oxaliplain- based Adam, 2001 Giacchetti, 1999 Giacchetti, 2000 Alberts, 2003 Tournigand, 2004 Irinotecan- based Pozo, 2004 Ducreux, 2003 Tournigand, 2004 OxIri- based Falcone, 2004 Quenet, %51%32%36%22%33%31% 9% 9%40%58% 14% 14% 38% 38% 21% 21% 33% 33% 13% 13% 28% 28% - 7% 7% 26% 26% 27% 27% 39%50% Resection rates after chemotherapy in initially inoperable patients Chemotherapy Pts Surgery R0 5-yr OS Chemotherapy Pts Surgery R0 5-yr OS rate rate

15 Resecabilità metastasi epatiche dopo 1^ linea Tournigand ( JCO 2004: ): FOLFIRI FOLFOX vs FOLFOX FOLFIRI Arm A Arm B FOLFIRI FOLFOX N° PZ N° responders61 59 N° resecati 8 21 R0/R17/113/8

16 Metastasi epatiche nel carcinoma del colon retto 1.Malattia solo epatica operata Cosa fare dopo resezione? –Solo follow up? –Chemioterapia locoregionale? –Chemioterapia sistemica? –Chemioterapia locoregionale + sistemica?

17 Metastasi epatiche nel carcinoma del colon retto

18 Trattamento adiuvante post-resettivo Necessario in ogni paziente resecato ? Dopo CT neoadiuvante sistemica ? Sola terapia sistemica ? Alternanza di CT sistemica di ultima generazione / CT i.a. meno tossica (5-FU) ?

19 Terapia sistemica CT sistemica con schedule basate sul 5-FU sembra poter dare beneficio ma le casistiche sono troppo limitate per dare risultati significativi

20 ADJUVANT THERAPY AFTER RESECTION OF LIVER METS FROM COLORECTAL-CANCER Author# ptsRegimensSurvHepatic Rec Free Lorenz HAI (LV/5-FU) Vs Control 47% 30% At 5 yrs ---- Kemeny N HAI (FuDR) + iv LVFU vs iv LVFU 61% 49% At 5 yrs 74% 44% Kemeny M 2002 (4 yrs F.up) 75/109 HAI (FuDR) + iv LVFU vs Control 63.7/47 mos 49/34 mos 67% 43%

21 Chemotherapy for resectable liver metastases HAI: 5FU/LV Observation 1.Lorenz et al, Ann Surg 1998;228:756; 2. Kemeny et al, J Clin Oncol 2002;20: ; 3. Kemeny et al, NEJM 1999;341:2039 HAI FUDR+ Systemic 5FU Observation HAI FUDR+Systemic 5FU/LV Systemic 5FU/LV German phase III 1 (N=34 evaluable/226 enrolled) ECOG/SWOG phase III 2 (N=75 evaluable/109 enrolled) MSKCC phase III 3 (N=156) No difference in TTP and OS, but results difficult to interpretate as only 30% of patients completed 4-yr liver PFS: 67% vs 43 (p=0.03) 4-yr OS: 62% VS 53% (NS) 2-yr liver PFS: 90% vs 60 (p=0.03) 2-yr OS: 86% vs 72% (p=0.03) 5-yr OS: 61% vs 45% S S S

22

23 Adjuvant HAI + SYS chemotherapy dopo metastasectomie multiple epatiche. Studio Fase II NCCTG 49 pts resected 44 % > 4 mets 78 % bilobar disease 12 % cryoablation 36 treated FUDR 0.2 mg / kg die 1 14 wks 0-2, 5-7, 10-12, Alternante Alternante MAYO classica wks 3 – 8 – Median FU = 6.2 yrs 25 / 36 recurred 5 yrs OS = 31 % 5 yrs liver free survival = 25 % Liver only 9 Extraliver only10 Both 9 MJ OConnel, Proc ASCO, Abs 3527, 2004

24 Chemioterapia neoadiuvante nelle metastasi epatiche resecabili Fattibile…ma a cosa serve ? Finestra biologica ? Ottimizzazione della durata del trattamento

25 Chemotherapy for resectable liver metastases: ongoing trials Systemic XELOX + HAI FUDR NSABP-C-09 phase III EORTC/EPOC phase III Systemic XELOX Accrual completed (N=360) Preliminary results will be communicated at ASCO 2005 S FOLFOX Observation FOLFOX R S

26 Phase III - Intergroup: Pre - and postoperative CT with oxaliplatin/5-FU/LV versus surgery alone in resectable liver metastases from CRC LV5FU2+L-OHP (6 cycles) surgery LV5FU2+L-OHP (6 cycles) R Surgery –Objectives: PFS, OS, Resection Rate, Toxicity –Sample Size: 330 pts in 3 y y follow-up –Start: June-July 2000 EORTC 40983

27 Contraindications for resection Unresectable extrahepatic disease Extensive liver involvement - > 6 segments involved - >70% liver parenchyma involved, or - all three hepatic veins involved Major liver insufficiency Patient unfit for or declining surgery Analysis of appropriateness Immediate resection Resection after pre-operative chemotherapy LOCAL DESTRUCTION CHEMOTHERAPY

28 LIVER M+ of CRC Unresectable Sinchronous or metachronous I.A. I.V. CT Responsive resectable SURG Responsive unresectable further CT Unresponsive 2nd-line CT

29 LIVER M+ of CRC Minimal residual unresectable liver disease after CT Radiofrequency TACE or TAE Surg + RF Further CT Follow-up Phase I trial

30 Conclusioni Le metastasi epatiche non sono tutte uguali.... e neppure i pazienti.....e neppure i medici Indispensabile la valutazione multidisciplinare di ogni caso Studio organico delle caratteristiche biologiche e di quelle cliniche

31


Scaricare ppt "Il trattamento delle metastasi epatiche neoplasie del colon retto Filippo de Braud MD Clinical Pharmacology and New Drugs Development Unit European Institute."

Presentazioni simili


Annunci Google